Obesity and cholangiocarcinoma: A review of epidemiological and molecular associations.
Osataphan Soravis,Mahankasuwan Treerat,Saengboonmee Charupong
Journal of hepato-biliary-pancreatic sciences
Cholangiocarcinoma (CCA) is a malignancy of bile duct epithelium, and its incidence is increasing globally. Numerous factors are reported associated with an increased risk of CCA and vary among populations across different areas. Obesity is a major, worldwide public health problem that leads to several complications and is associated with increased cancer risk. Although several epidemiological studies have shown that obesity is likely associated with the increased risk of CCA, this association might be limited to Western countries. Multiple hormones, cytokines, and metabolite perturbations in obese states have been shown to enhance tumorigenicity and metastasis potentials. Understanding the biological linkage of obesity to CCA might lead to novel prevention and therapeutic approaches to CCA treatment. This review summarizes the current evidence and highlights the knowledge gaps regarding the relationship between obesity and CCA from epidemiological and molecular perspectives.
Neuromusculoskeletal Health in Pediatric Obesity: Incorporating Evidence into Clinical Examination.
O'Malley Grace C,Shultz Sarah P,Thivel David,Tsiros Margarita D
Current obesity reports
PURPOSE OF REVIEW:The study aims to highlight the clinical importance of assessing and managing neuromusculoskeletal health in pediatric obesity and to support translation of evidence into practice. RECENT FINDINGS:A growing evidence base suggests that children with obesity experience neuromusculoskeletal impairments and physical complications including increased pain, reduced muscle strength, impaired balance and motor skill, gait deviations, postural malalignment, greater fatigue, and potentially reduced flexibility and sub-optimal bone health. Such evidence supports the need to screen, assess, and optimize neuromusculoskeletal health as part of pediatric obesity management. The likelihood of children with obesity experiencing neuromusculoskeletal impairments is high and can impact the way a child moves, and their interest or capacity to engage in physical activity and exercise. Barriers to movement should be minimized to promote optimal development of the neuromusculoskeletal system and to support engagement in sufficient physical activity for weight management. Healthcare professionals should screen for neuromusculoskeletal impairments as well as personalize interventions and modify standardized exercise interventions to optimize obesity treatment. Further research should explore whether neuromusculoskeletal impairments influence the success of obesity treatment or whether they improve following obesity treatment.
Association of Obesity and Incidence of Third, Fourth, and Sixth Cranial Nerve Palsies.
Choi Daye Diana,Han Kyungdo,Park Kyung-Ah,Oh Sei Yeul
American journal of ophthalmology
STUDY DESIGN:Retrospective cohort study. OBJECTIVE:To assess the association between obesity and the development of third, fourth, and sixth cranial nerve palsy (CNP). METHODS:We analyzed a cohort of 4,067,842 adults aged between 20 and 90 years who underwent health checkups within the National Health Insurance Service between January 1 and December 31, 2009. The participants were followed until December 31, 2017. Cox proportional hazards regression analysis was used to determine the adjusted hazard ratios (HRs) for CNP. Model 3 (the main analysis model) was adjusted for age, sex, smoking status, alcohol consumption, and physical activity. Model 4 was additionally adjusted for hypertension, dyslipidemia, and diabetes mellitus in the setting of model 3. RESULTS:A total of 5,835 individuals were diagnosed with CNP during the follow-up period (7.3 years). General obesity (body mass index [BMI] ≥25 kg/m) was associated with an increased risk of CNP compared to individuals without general obesity (model 3, HR 1.248, 95% CI 1.184-1.315; model 4, HR 1.162, 95% CI 1.102-1.227). Abdominal obesity (waist circumference [WC] ≥90 cm in men and ≥85 cm in women) also showed an increased HR compared to individuals without abdominal obesity (model 3, 1.239, 95% CI 1.170-1.313; model 4, HR 1.127, 95% CI 1.062-1.196). Compared to the group without either type of obesity, the group with only abdominal obesity (model 3, HR 1.167, 95% CI 1.035-1.317), the group with only general obesity (HR 1.19, 95% CI 1.14-1.24), and the group with both obesity types (HR 1.317, 95% CI 1.236-1.404) showed increased HRs for CNP. CONCLUSION:Based on our population-based cohort study, both general and abdominal obesity increased the risk of CNP. Also, the combination of general and abdominal obesity may further increase the risk of CNP.
A natural anti-obesity reagent derived from sea buckthorn polysaccharides: Structure characterization and anti-obesity evaluation in vivo.
Ma Zhiyuan,Sun Qingyang,Chang Lili,Peng Jing,Zhang Mengqi,Ding Xuechao,Zhang Qiang,Liu Guoku,Liu Xuebo,Lan Ying
Sea buckthorn polysaccharide (SBP) has received increasing attention for its various bioactive functions. In this study, a novel polysaccharide SBP-1 was initially separated from crude SBP and further purified to obtain its main fraction SBP-1-A with a Mw of 9944 Da, consisting of Rha, Ara, Gal, Glc, and GalA. The structure of SBP-1-A was characterized based on FT-IR, GC-MS, and 1D/2D NMR, and its backbone was composed of a repeated unit of → 3,4)-β-l-Rhap-(1 → 4)-α-d-GalAp-(1 → 4)-α-d-GalAp-(1 → with branches at C-4 position comprised of α-l-Araf, β-d-Galp, β-d-Glcp, α-d-Glcp. Besides, the anti-obesity effects of SBP-1 on high-fat diet mice were evaluated, indicating it could restrain the body weight gain and lipids accumulation by promoting the expression of PGC1α, UCP-1, and PRDM16 to activate the brown adipocyte and improve the thermogenesis. In summary, the results offered new supports for the structural information of SBP and its feasibility to be used as a natural anti-obesity reagent.
Comorbid depression and obesity among adults in Germany: Effects of age, sex, and socioeconomic status.
Chae Woo Ri,Schienkiewitz Anja,Du Yong,Hapke Ulfert,Otte Christian,Michalski Niels
Journal of affective disorders
BACKGROUND:Depression and obesity are common health problems with major public health implications. These conditions frequently co-occur, adversely affecting the course of the other. The sociodemographic and socioeconomic risk factors for comorbid depression and obesity in the German adult population have not yet been reported. METHODS:We analyzed the prevalence and sociodemographic and socioeconomic correlates of comorbid depression and obesity using cross-sectional data from the national German health interview and examination survey for adults (DEGS1; n = 7987) and its mental health module (DEGS1-MH; n = 4493). The Composite International Diagnostic Interview was used to diagnose major depressive disorder (CIDI-MDD). Sensitivity was analyzed using the self-reported depression measure and current depressive symptoms measured by Patient Health Questionnaire-9 (PHQ-9). Obesity was defined by body mass index calculated from measured data. RESULTS:Prevalence of comorbid depression and obesity was 1.3% (95% CI 0.8-2.0) in men and 2.0% (95% CI 1.3-3.0) in women. We found significant sex differences in results from the self-reported depression measure and the PHQ-9, but not from the CIDI-MDD. Low socioeconomic status and poor social support were linked to a higher prevalence of comorbid depression and obesity among women. LIMITATIONS:Severe depression may have been underreported. CONCLUSIONS:Depression is statistically more prevalent in women than in men, which accounts for many of the sex differences in the prevalence of comorbid depression and obesity in our models. Targeted public health strategies need to be developed to prevent and treat comorbid depression and obesity in women with a low socioeconomic position.
m6A Regulators in Human Adipose Tissue - Depot-Specificity and Correlation With Obesity.
Rønningen Torunn,Dahl Mai Britt,Valderhaug Tone Gretland,Cayir Akin,Keller Maria,Tönjes Anke,Blüher Matthias,Böttcher Yvonne
Frontiers in endocrinology
Background:N-methyladenosine (m6A) is one of the most abundant post-transcriptional modifications on mRNA influencing mRNA metabolism. There is emerging evidence for its implication in metabolic disease. No comprehensive analyses on gene expression of m6A regulators in human adipose tissue, especially in paired adipose tissue depots, and its correlation with clinical variables were reported so far. We hypothesized that inter-depot specific gene expression of m6A regulators may differentially correlate with clinical variables related to obesity and fat distribution. Methods:We extracted intra-individually paired gene expression data (omental visceral adipose tissue (OVAT) =48; subcutaneous adipose tissue (SAT) =56) of m6A regulators from an existing microarray dataset. We also measured gene expression in another sample set of paired OVAT and SAT (=46) using RT-qPCR. Finally, we extracted existing gene expression data from peripheral mononuclear blood cells (PBMCs) and single nucleotide polymorphisms (SNPs) in and from genome wide data from the Sorbs population (=1049). The data were analysed for differential gene expression between OVAT and SAT; and for association with obesity and clinical variables. We further tested for association of SNP markers with gene expression and clinical traits. Results:In adipose tissue we observed that several m6A regulators (, , and ) correlate with obesity and clinical variables. Moreover, we found adipose tissue depot specific gene expression for , , , and In PBMCs, we identified and correlated with obesity. Genetic markers in associate with BMI whilst SNPs in are associated with its gene expression. Conclusions:Our data show that expression of m6A regulators correlates with obesity, is adipose tissue depot-specific and related to clinical traits. Genetic variation in m6A regulators adds an additional layer of variability to the functional consequences.
Visceral adiposity, inflammation, and hippocampal function in obesity.
The 'apple-shaped' anatomical pattern that accompanies visceral adiposity increases risk for multiple chronic diseases, including conditions that impact the brain, such as diabetes and hypertension. However, distinguishing between the consequences of visceral obesity, as opposed to visceral adiposity-associated metabolic and cardiovascular pathologies, presents certain challenges. This review summarizes current literature on relationships between adipose tissue distribution and cognition in preclinical models and highlights unanswered questions surrounding the potential role of tissue- and cell type-specific insulin resistance in these effects. While gaps in knowledge persist related to insulin insensitivity and cognitive impairment in obesity, several recent studies suggest that cells of the neurovascular unit contribute to hippocampal synaptic dysfunction, and this review interprets those findings in the context of progressive metabolic dysfunction in the CNS. Signalling between cerebrovascular endothelial cells, astrocytes, microglia, and neurons has been linked with memory deficits in visceral obesity, and this article describes the cellular changes in each of these populations with respect to their role in amplification or diminution of peripheral signals. The picture emerging from these studies, while incomplete, implicates pro-inflammatory cytokines, insulin resistance, and hyperglycemia in various stages of obesity-induced hippocampal dysfunction. As in the parable of the five blind wanderers holding different parts of an elephant, considerable work remains in order to assemble a model for the underlying mechanisms linking visceral adiposity with age-related cognitive decline.
Diallyl Trisulfide Prevents Obesity and Decreases miRNA-335 Expression in Adipose Tissue in a Diet-Induced Obesity Rat Model.
Miura Atsushi,Ikeda Ayana,Abe Marina,Seo Kiki,Watanabe Takahiro,Ozaki-Masuzawa Yori,Hosono Takashi,Seki Taiichiro
Molecular nutrition & food research
SCOPE:Diallyl trisulfide (DATS), an organosulfur compound generates in crushed garlic, has various beneficial health effects. A growing body of evidence indicates that miRNAs are involved in the pathology of lifestyle diseases including obesity. The anti-obesogenic effect of garlic is previously reported; however, the effects of DATS on obesity, and the relationship between garlic compounds and the involvement of miRNA remains unclear. Here, the anti-obesogenic activity of DATS and the potential role of miRNA in a diet-induced obesity rat model are investigated. METHODS AND RESULTS:Oral administration of DATS suppressed body and white adipose tissue (WAT) weight gain in rats fed a high-fat diet compared with vehicle-administered rats. DATS lowered the plasma and liver triglyceride levels in obese rats, and decreased lipogenic mRNA levels including those of Srebp1c, Fasn, and Scd1 in the liver. DATS also suppressed de novo lipogenesis in the liver. Transcriptomic analyses of miRNA and mRNA in the epididymal WAT of obese rats using microarrays revealed that DATS decreased miRNA-335 expression and normalized the obesity-related mRNA transcriptomic signatures in epididymal WAT. CONCLUSION:The potent anti-obesogenic effects of DATS and its possible mechanism of action was clearly demonstrated in this study.
Semaglutide for the treatment of obesity.
Trends in cardiovascular medicine
Semaglutide is a glucagon-like peptide-1 receptor agonist that was recently approved by the US Food and Drug Administration for chronic weight management. This paper reviews data on the mechanism of action, weight-loss and cardiometabolic efficacy, and safety of semaglutide 2.4 mg/week for obesity. Semaglutide has demonstrated the largest weight loss of any obesity medication to date with reductions of approximately 15% of initial weight at 68 weeks, accompanied by improvements in cardiovascular risks factors and physical functioning. The approval of this medication provides patients with greater options for weight management.
The sociocultural mechanism of obesity: The influence of gender role attitudes on obesity and the gender gap.
He Jun,Xie Yongxiang
Social science & medicine (1982)
Worldwide, women are more likely to be obese than men, but research on the mechanism of the gender gap in obesity is relatively lacking. This article uses five rounds of Chinese General Social Survey (CGSS) data from 2010 to 2017 to empirically test the impact of gender role attitudes on obesity and the gender gap and to explore the mechanism. The main results show that the traditional gender role attitude will improve the probability of obesity in women, but it will not positively impact obesity in men. Using the proportion of "March 8th red flag bearer" at the provincial level as an instrumental variable to alleviate the possible estimation errors caused by omitted variables, the results show that the lower the proportion of red flag bearers, the higher the probability of obesity of women, and still will not improve the probability of obesity of men. The robustness test based on the generalized propensity score method (GPSM) supports the above results. The mechanism analysis shows that economic status and market participation are two essential mechanisms of gender role attitudes and female obesity. Traditional gender role attitudes increase the risk of women's obesity by reducing their economic status and labour market participation.
Is obesity in the brain? Parent perceptions of brain influences on obesity.
Neuroimaging studies demonstrate associations of brain structure and function with children's eating behaviour and body weight, and the feasibility of integrating brain measures into obesity risk assessment and intervention is growing. However, little is known about lay perceptions of how the brain influences obesity. We investigated parent perceptions of brain contributions to obesity in three separate studies: 1) a study of mothers of adolescents recruited for neuroimaging research (n = 88), 2) a study of ethnically Chinese parents of 5-13 year olds participating in a parent feeding survey (n = 277), and 3) a study of parents of 3-15 year olds completing an online survey (n = 113). In general, parents believed that brain factors influence obesity, but considered them less influential than behaviours such as diet and exercise. Causal attributions for brain factors were correlated with attributions for genetic factors and biological factors (e.g., metabolism). Parents who perceived their child to be overweight or had a high concern about their child becoming overweight in the future rated brain factors as more important in determining their child's weight and more likely to lessen their child's ability to control their weight. Our results suggest that parents attribute obesity to the brain to a moderate degree, and that education or feedback regarding brain influences on obesity could be a promising obesity intervention component.
Long-Term Weight Loss Strategies for Obesity.
Kheniser Karim,Saxon David R,Kashyap Sangeeta R
The Journal of clinical endocrinology and metabolism
CONTEXT:Obesity is a chronic disease that is difficult to manage without holistic therapy. The therapeutic armamentarium for obesity primarily consists of 4 forms of therapy: lifestyle modification (ie, diet and exercise), cognitive behavioral therapy, pharmacotherapy, and bariatric surgery. EVIDENCE ACQUISITION:Evidence was consolidated from randomized controlled trials, observational studies, and meta-analyses. EVIDENCE SYNTHESIS:After 2 years, lifestyle interventions can facilitate weight loss that equates to ~5%. Even though lifestyle interventions are plagued by weight regain, they can have substantial effects on type 2 diabetes and cardiovascular disease risk. Although 10-year percentage excess weight loss can surpass 50% after bariatric surgery, weight regain is likely. To mitigate weight regain, instituting a multifactorial maintenance program is imperative. Such a program can integrate diet, exercise, and pharmacotherapy. Moreover, behavioral therapy can complement a maintenance program well. CONCLUSIONS:Obesity is best managed by a multidisciplinary clinical team that integrates diet, exercise, and pharmacotherapy. Bariatric surgery is needed to manage type 2 diabetes and obesity in select patients.
Possible Benefits of for Obesity-Associated Gut Disorders.
Maioli Tatiani Uceli,Borras-Nogues Esther,Torres Licia,Barbosa Sara Candida,Martins Vinicius Dantas,Langella Philippe,Azevedo Vasco Ariston,Chatel Jean-Marc
Frontiers in pharmacology
Metabolic disorders are an increasing concern in the industrialized world. Current research has shown a direct link between the composition of the gut microbiota and the pathogenesis of obesity and diabetes. In only a few weeks, an obesity-inducing diet can lead to increased gut permeability and microbial dysbiosis, which contributes to chronic inflammation in the gut and adipose tissues, and to the development of insulin resistance. In this review, we examine the interplay between gut inflammation, insulin resistance, and the gut microbiota, and discuss how some probiotic species can be used to modulate gut homeostasis. We focus primarily on , a highly abundant butyrate-producing bacterium that has been proposed both as a biomarker for the development of different gut pathologies and as a potential treatment due to its production of anti-inflammatory metabolites.
Obesity, Inflammation, and Severe Asthma: an Update.
Sharma Varun,Cowan Douglas C
Current allergy and asthma reports
PURPOSE OF REVIEW:Obesity-associated difficult asthma continues to be a substantial problem and, despite a move to address treatable traits affecting asthma morbidity and mortality, it remains poorly understood with limited phenotype-specific treatments. The complex association between asthma, obesity, and inflammation is highlighted and recent advances in treatment options explored. RECENT FINDINGS:Obesity negatively impacts asthma outcomes and has a causal link in the pathogenesis of adult-onset asthma. Imbalance in the adipose organ found in obesity favours a pro-inflammatory state both systemically and in airways. Obesity may impact currently available asthma biomarkers, and obesity-associated asthma specific biomarkers are needed. Whilst surgical weight loss interventions are associated with improvements in asthma control and quality of life, evidence for pragmatic conservative options are sparse. Innovative approaches tackling obesity-mediated airway inflammation may provide novel therapies. The immunopathological mechanisms underlying obesity-associated asthma require further research that may lead to novel therapeutic options for this disease. However, weight loss appears to be effective in improving asthma in this cohort and focus is also needed on non-surgical treatments applicable in the real-world setting.
Dietary flavonoid kaempferol reduces obesity-associated hypothalamic microglia activation and promotes body weight loss in mice with obesity.
BACKGROUND:Obesity results from an unbalance in the ingested and burned calories. Energy balance (EB) is critically regulated by the hypothalamic arcuate nucleus (ARC) by promoting appetite or anorectic actions. Hypothalamic inflammation, driven by high activation of the microglia, has been reported as a key mechanism involved in the development of diet-induced obesity. Kaempferol (KF), a flavonoid-type polyphenol present in a large number of fruits and vegetables, was shown to regulate both energy metabolism and inflammation. OBJECTIVES:In this work, we studied the effects of both the central and peripheral treatment with KF on hypothalamic inflammation and EB regulation in mice with obesity. METHODS:Obese adult mice were chronically (40 days) treated with KF (0.5 mg/kg/day, intraperitoneally). During the treatment, body weight, food intake (FI), feed efficiency (FE), glucose tolerance, and insulin sensitivity were determined. Analysis of microglia activation in the ARC of the hypothalamus at the end of the treatment was also performed. Body weight, FI, and FE changes were also evaluated in response to 5µg KF, centrally administrated. RESULTS:Chronic administration of KF decreased ∼43% of the density, and ∼30% of the ratio, of activated microglia in the arcuate nucleus. These changes were accompanied by body weight loss, decreased FE, reduced fasting blood glucose, and a tendency to improve insulin sensitivity. Finally, acute central administration of KF reproduced the effects on EB triggered by peripheral administration. CONCLUSION:These findings suggest that KF might fight obesity by regulating central processes related to EB regulation and hypothalamic inflammation.
Obesity, Diabetes, and Increased Cancer Progression.
Diabetes & metabolism journal
Rates of obesity and diabetes have increased significantly over the past decades and the prevalence is expected to continue to rise further in the coming years. Many observations suggest that obesity and diabetes are associated with an increased risk of developing several types of cancers, including liver, pancreatic, endometrial, colorectal, and post-menopausal breast cancer. The path towards developing obesity and diabetes is affected by multiple factors, including adipokines, inflammatory cytokines, growth hormones, insulin resistance, and hyperlipidemia. The metabolic abnormalities associated with changes in the levels of these factors in obesity and diabetes have the potential to significantly contribute to the development and progression of cancer through the regulation of distinct signaling pathways. Here, we highlight the cellular and molecular pathways that constitute the links between obesity, diabetes, cancer risk and mortality. This includes a description of the existing evidence supporting the obesity-driven morphological and functional alternations of cancer cells and adipocytes through complex interactions within the tumor microenvironment.
Dysfunction of resolution receptor triggers cardiomyopathy of obesity and signs of non-resolving inflammation in heart failure.
Molecular and cellular endocrinology
Heart failure with preserved ejection fraction (HFpEF) has been an emerging type of cardiac disease since the pseudo-left ventricle function is preserved; therefore, challenges in finding the target and treatment. Damage and pathogen-associated molecular patterns (DAMPs and PAMPs) are widely investigated in acute and chronic inflammation in heart failure; however, lifestyle-associated molecular patterns (LAMPs: diet, sleep, exercise), particularly in obesity, remains of interest due to the enormous increase of HFpEF patients. In this review, we covered obesity-related cardiomyopathy, LAMPs, and resolution receptor dysfunction in the context of heart failure with preserved ejection fraction.
Examining the influence of positive childhood experiences on childhood overweight and obesity using a national sample.
Positive childhood experiences (PCEs) promote healthy social development, improve overall wellness, and help to moderate and prevent exposure to adverse childhood experiences. There has been limited research examining the association between positive childhood experiences and overweight or obesity status in children. The purpose of this study was to examine whether experiencing positive childhood experiences are associated with lower rates of overweight or obesity status in children between 10 and 17 years of age, using cross-sectional data from the 2018-2019 National Survey of Children's Health (n = 28,771), a nationally representative mail and online survey. Frequencies, proportions, and unadjusted associations for each variable were calculated using descriptive statistics and bivariate analyses. To examine the association between overweight or obesity and PCEs, multivariable regression models were used. Compared to children who were underweight or had a healthy weight, children who were overweight or obese were less likely to: participate after school activities (78.1%, p < 0.0001), volunteer in their community, school, or church (45.6%, p < 0.0001), have a mentor they feel comfortable going to for guidance (87.0%, p = 0.02), live in a safe neighborhood (61.3%, p < 0.0001), live in a supportive neighborhood (50.4%, p < 0.0001), and to live with a resilient family (78.3%; p = 0.0099). In adjusted analysis, among children exposed to two or more ACEs, children residing in a supportive neighborhood were less likely to be overweight or obese (aOR 0.87; 0.77-0.98). Our findings suggest that certain PCEs may mitigate overweight and obesity when children have experienced at least some childhood trauma.
Insulin Increases Adipose Adiponectin in Pregnancy by Inhibiting Ubiquitination and Degradation: Impact of Obesity.
The Journal of clinical endocrinology and metabolism
CONTEXT:Circulating adiponectin levels are decreased in pregnant women with obesity or gestational diabetes, and this is believed to contribute to the insulin resistance and increased risk of fetal overgrowth associated with these conditions. However, the molecular mechanisms regulating adiponectin secretion from maternal adipose tissues in pregnancy are poorly understood. OBJECTIVE:We tested the hypothesis that obesity in pregnancy is associated with adipose tissue insulin resistance and increased adiponectin ubiquitination and degradation, caused by inflammation and endoplasmic reticulum (ER) stress. METHODS:Visceral adipose tissues were collected from lean and obese pregnant humans and mice. Total and ubiquitinated adiponectin, and markers of inflammation, ER stress, and insulin resistance were examined in adipose tissues. The role of insulin, inflammation, and ER stress in mediating adiponectin ubiquitination and degradation was examined using 3T3L-1 adipocytes. RESULTS:Obesity in pregnancy is associated with adipose tissue inflammation, ER stress, insulin resistance, increased adiponectin ubiquitination, and decreased total abundance of adiponectin. Adiponectin ubiquitination was increased in visceral fat of obese pregnant women as compared to lean pregnant women. We further observed that insulin prevents, whereas ER stress and inflammation promote, adiponectin ubiquitination and degradation in differentiated 3T3-L1 adipocytes. CONCLUSION:We have identified adiponectin ubiquitination as a key mechanism by which obesity diminishes adiponectin secretion in pregnancy. This information will help us better understand the mechanisms controlling maternal insulin resistance and fetal growth in pregnancy and may provide a foundation for the development of strategies aimed at improving adiponectin production in pregnant women with obesity or gestational diabetes.
Obesity and Kidney Function: A Two-Sample Mendelian Randomization Study.
BACKGROUND:Obesity and type 2 diabetes (T2D) are correlated risk factors for chronic kidney disease (CKD). METHODS:Using summary data from GIANT (Genetic Investigation of Anthropometric Traits), DIAGRAM (DIAbetes Genetics Replication And Meta-analysis), and CKDGen (CKD Genetics), we examined causality and directionality of the association between obesity and kidney function. Bidirectional 2-sample Mendelian randomization (MR) estimated the total causal effects of body mass index (BMI) and waist-to-hip ratio (WHR) on kidney function, and vice versa. Effects of adverse obesity and T2D were examined by stratifying BMI variants by their association with WHR and T2D. Multivariable MR estimated the direct causal effects of BMI and WHR on kidney function. The inverse variance weighted random-effects MR for Europeans was the main analysis, accompanied by several sensitivity MR analyses. RESULTS:One standard deviation (SD ≈ 4.8 kg/m2) genetically higher BMI was associated with decreased estimated glomerular filtration rate (eGFR) [β=-0.032 (95% confidence intervals: -0.036, -0.027) log[eGFR], P = 1 × 10-43], increased blood urea nitrogen (BUN) [β = 0.010 (0.005, 0.015) log[BUN], P = 3 × 10-6], increased urinary albumin-to-creatinine ratio [β = 0.199 (0.067, 0.332) log[urinary albumin-to-creatinine ratio (UACR)], P = 0.003] in individuals with diabetes, and increased risk of microalbuminuria [odds ratios (OR) = 1.15 [1.04-1.28], P = 0.009] and CKD [1.13 (1.07-1.19), P = 3 × 10-6]. Corresponding estimates for WHR and for trans-ethnic populations were overall similar. The associations were driven by adverse obesity, and for microalbuminuria additionally by T2D. While genetically high BMI, unlike WHR, was directly associated with eGFR, BUN, and CKD, the pathway to albuminuria was likely through T2D. Genetically predicted kidney function was not associated with BMI or WHR. CONCLUSIONS:Genetically high BMI is associated with impaired kidney function, driven by adverse obesity, and for albuminuria additionally by T2D.
A randomized study of effects of obesity framing on weight stigma.
Obesity (Silver Spring, Md.)
OBJECTIVE:Growing evidence suggests highly processed foods may trigger an addictive-like process, which is associated with obesity. Other research suggests an addictive-like process occurs in response to eating itself, rather than specific foods. Addiction-based obesity explanations raise concerns about double stigmatization of people with obesity and addiction. This study compared effects of obesity framings on external and internalized weight stigma. METHODS:The study was preregistered via Open Science Framework. Four hundred and forty-seven adults read an informational passage that described food addiction, eating addiction, or calorie balance explanations for obesity or a control passage about memory. Participants then completed external and internalized weight stigma measures. RESULTS:Participants in the food addiction condition reported higher internalized weight stigma compared with those in the control condition. Obesity framing did not significantly affect external weight stigma compared with the control. CONCLUSIONS:These findings suggest that food addiction explanations for obesity may elicit greater internalized weight stigma than non-obesity-related messages. Addiction-based and traditional obesity explanations do not appear to influence external weight stigma. Illuminating the effects of obesity framing on stigma will help researchers communicate discoveries in ways that mitigate stigma.
C-section birth increases offspring obesity risk dependent on maternal diet and obesity status in rats.
Cho Nicole A,Sales Kate M,Sampsell Kara,Wang Weilan,Noye Tuplin Erin W,Lowry Dana E,Reimer Raylene A
Obesity (Silver Spring, Md.)
OBJECTIVE:The gut microbiota is a complex ecosystem that shapes host metabolism, especially in early life. Maternal vaginal and gut microbiota is vertically transmitted to offspring during natural birth. Offspring born by cesarean section (CS) do not receive these bacteria and exhibit higher obesity risk later in life. The objective of this study was to examine differences in obesity risk between offspring born naturally (NB) or by CS to lean/obese dams. METHODS:Lean and obese rat dams gave birth to offspring naturally or by CS. Offspring obesity risk was analyzed via body weight/composition, food intake, sucrose preference, gut microbiota, and gene expression in gut and brain tissues. RESULTS:Obese (O)+CS offspring showed greater weight gain and caloric intake but a reduction in hypothalamic agouti related neuropeptide, neuropeptide Y, and interleukin 1β expression compared with O+NB offspring. Lean (L)+CS offspring had higher serum corticosterone concentration and reduced liver peroxisome proliferator-activated receptor γ expression compared with L+NB. O+CS offspring had long-term alterations to gut microbiota, including increased relative abundance of Faecalibaculum and reduced Muribaculaceae. CONCLUSIONS:Overall, CS alters obesity risk differentially based on maternal obesity status. Further studies looking at the risks of obesity associated with CS are needed, with special attention paid to maternal obesity status and gut microbiota.
Rolling out physical exercise and energy homeostasis: Focus on hypothalamic circuitries.
Cavalcanti-de-Albuquerque João Paulo,Donato José
Frontiers in neuroendocrinology
Energy balance is the fine regulation of energy expenditure and energy intake. Negative energy balance causes body weight loss, while positive energy balance promotes weight gain. Modern societies offer a maladapted way of life, where easy access to palatable foods and the lack of opportunities to perform physical activity are considered the roots of the obesity pandemic. Physical exercise increases energy expenditure and, consequently, is supposed to promote weight loss. Paradoxically, physical exercise acutely drives anorexigenic-like effects, but the mechanisms are still poorly understood. Using an evolutionary background, this review aims to highlight the potential involvement of the melanocortin system and other hypothalamic neural circuitries regulating energy balance during and after physical exercise. The physiological significance of these changes will be explored, and possible signalling agents will be addressed. The knowledge discussed here might be important for clarifying obesity aetiology as well as new therapeutic approaches for body weight loss.
Association Between Obesity and Microvascular Diseases in Patients With Type 2 Diabetes Mellitus.
Gao Shan,Zhang Hongliang,Long Chen,Xing Zhenhua
Frontiers in endocrinology
This study aimed to evaluate the association between obesity, evaluated by fat mass index (FMI) with the risk of microvascular diseases in patients with type 2 diabetes mellitus (T2DM) and compare the magnitude of associations of FMI, body mass index (BMI), and waist circumference (WC) with the risk of microvascular diseases. We performed a analysis of the Action to Control Cardiovascular Risk in Diabetes study. The primary microvascular outcomes of the present study included chronic kidney disease (CKD) progression, retinopathy, and neuropathy. Cox proportional-hazards models were performed to evaluate the association of FMI with microvascular diseases. A discordant analysis was performed to compare the magnitude of associations of FMI, BMI, and WC with the risk of microvascular diseases. Our study included 10,251 T2DM participants with a median of 5 years (interquartile range, 4.2-5.7) of follow-up. A total of 6,184 participants developed CKD progression, 896 participants had retinopathy, and 3,213 participants developed neuropathy (Michigan Neuropathy Screening Instrument, >2.0). After the confounding factors were adjusted for, patients in the highest FMI quartile had a higher risk of CKD progression (HR: 1.26, 95%CI: 1.16-1.36) and neuropathy (HR: 1.93, 95% CI: 1.74-2.15), except for retinopathy (HR: 1.17, 95% CI: 0.96-1.43), than those in the lowest quartile. Discordant analyses found that FMI and WC are better in identifying individuals with obesity-related risk of neuropathy, compared with BMI; neither is better in identifying individuals with obesity-related risk of CKD progression and retinopathy. Obesity is associated with CKD progression and neuropathy in T2DM participants. Further randomized trials are needed to test whether obesity control can improve the outcomes of T2DM participants with CKD or neuropathy. FMI and WC are more useful in identifying obesity-related risk of neuropathy compared with BMI in T2DM patients. Clinical Trial Registration:http://www.clinicaltrials.gov, NCT00000620.
Metabolically healthy obesity was significantly associated with increased risk of gallstones.
European journal of endocrinology
OBJECTIVE:The risk of gallstones among metabolically healthy obesity (MHO) individuals is largely unexplored. Therefore, the present study investigated the association between MHO and gallstones in a health check-up cohort of Chinese adults. DESIGN:A prospective cohort study. METHODS:Participants included 58 862 individuals from the MJ health check-up cohort aged ≥ 18 years without a history of gallstones at baseline. Gallstones were diagnosed using abdominal B-type ultrasound. Metabolically healthy was defined as not having any one of the components of metabolic syndrome. Obesity was identified by BMI and waist circumference (WC). Participants were cross-classified at baseline by metabolic health and obesity. Adjusted hazard ratios (HRs) and 95% CIs of gallstones across BMI or WC categories were estimated with Cox proportional hazard regression models. RESULTS:During a median follow-up of 3.0 years (interquartile range, 1.6-6.1), 1269 participants developed gallstones. Individuals with MHO (HR: 1.95, 95% CI: 1.23, 3.09 for BMI criteria; HR: 1.74, 95% CI: 1.37, 2.21 for WC criteria) had a significantly higher risk of gallstones than those with metabolically healthy normal weight. In metabolically healthy individuals, BMI and WC both displayed linear dose-response relationships with gallstones (P for non-linearity >0.05). The association between MHO and gallstones remained unchanged when using different criteria for metabolic health and obesity. CONCLUSIONS:MHO was significantly associated with gallstones, suggesting that obesity can independently contribute to gallstones development, even among metabolically healthy individuals. These findings emphasize that metabolically healthy individuals may still benefit from maintaining normal body weight to prevent gallstones.
Targeting obesity-related dysfunction in hormonally driven cancers.
British journal of cancer
Obesity is a risk factor for at least 13 different types of cancer, many of which are hormonally driven, and is associated with increased cancer incidence and morbidity. Adult obesity rates are steadily increasing and a subsequent increase in cancer burden is anticipated. Obesity-related dysfunction can contribute to cancer pathogenesis and treatment resistance through various mechanisms, including those mediated by insulin, leptin, adipokine, and aromatase signalling pathways, particularly in women. Furthermore, adiposity-related changes can influence tumour vascularity and inflammation in the tumour microenvironment, which can support tumour development and growth. Trials investigating non-pharmacological approaches to target the mechanisms driving obesity-mediated cancer pathogenesis are emerging and are necessary to better appreciate the interplay between malignancy, adiposity, diet and exercise. Diet, exercise and bariatric surgery are potential strategies to reverse the cancer-promoting effects of obesity; trials of these interventions should be conducted in a scientifically rigorous manner with dose escalation and appropriate selection of tumour phenotypes and have cancer-related clinical and mechanistic endpoints. We are only beginning to understand the mechanisms by which obesity effects cell signalling and systemic factors that contribute to oncogenesis. As the rates of obesity and cancer increase, we must promote the development of non-pharmacological lifestyle trials for the treatment and prevention of malignancy.
Dynamic regulation of N,2'-O-dimethyladenosine (mAm) in obesity.
The prevalent mAm mRNA cap modification was recently identified as a valid target for removal by the human obesity gene FTO along with the previously established mA mRNA modification. However, the deposition and dynamics of mAm in regulating obesity are unknown. Here, we investigate the liver mA/m methylomes in mice fed on a high fat Western-diet and in ob/ob mice. We find that FTO levels are elevated in fat mice, and that genes which lost mAm marking under obesity are overly downregulated, including the two fatty-acid-binding proteins FABP2, and FABP5. Furthermore, the cellular perturbation of FTO correspondingly affect protein levels of its targets. Notably, generally mAm- but not mA-methylated genes, are found to be highly enriched in metabolic processes. Finally, we deplete all mA background via Mettl3 knockout, and unequivocally uncover the association of mAm methylation with increased mRNA stability, translation efficiency, and higher protein expression. Together, these results strongly implicate a dynamic role for mAm in obesity-related translation regulation.
ER stress in obesity pathogenesis and management.
Trends in pharmacological sciences
Given the unprecedented global pandemic of obesity, a better understanding of the etiology of adiposity will be necessary to ensure effective management of obesity and related complications. Among the various potential factors contributing to obesity, endoplasmic reticulum (ER) stress refers to a state of excessive protein unfolding or misfolding that is commonly found in metabolic diseases including diabetes mellitus, insulin resistance (IR), and non-alcoholic fatty liver disease, although its role in obesogenesis remains controversial. ER stress is thought to drive adiposity by dampening energy expenditure, making ER stress a likely therapeutic target for the management of obesity. We summarize the role of ER stress and the ER stress response in the onset and development of obesity, and discuss the underlying mechanisms involved with a view to identifying novel therapeutic strategies for obesity prevention and management.
Exercise facilities and the prevalence of obesity and type 2 diabetes in the city of Madrid.
Cereijo Luis,Gullón Pedro,Del Cura Isabel,Valadés David,Bilal Usama,Badland Hannah,Franco Manuel
AIMS/HYPOTHESIS:We aimed to study the association between the availability of exercise facilities and the likelihood of obesity and type 2 diabetes in the adult population of Madrid, Spain. METHODS:We analysed the electronic medical records of all 1,270,512 residents of Madrid aged 40-75 years in 2017. Exercise facility availability was defined as the count of exercise facilities in a 1000 m street network buffer around each residential building entrance. Poisson regression with standard errors clustered at census tract level was used to assess prevalence ratios of exercise facility availability tertiles and obesity and type 2 diabetes. We also examined stratified results by tertiles of area-level socioeconomic status (SES) and sex. RESULTS:People living in areas with lower availability of exercise facilities had a higher prevalence of obesity (prevalence ratio [PR] 1.22 [95% CI 1.20, 1.25]) and diabetes (PR 1.38 [95% CI 1.34, 1.43]). We observed effect modification by area-level SES (p<0.001), with stronger associations for residents living in low-SES areas and no association for residents living in high-SES areas. Associations with type 2 diabetes were stronger among women compared with men, while associations with obesity were similar by sex. CONCLUSIONS/INTERPRETATION:People living in areas with low availability of exercise facilities had a higher prevalence of obesity and type 2 diabetes, and this association was strongest in low-SES areas and for women. Understanding the potential role of exercise facilities in driving inequities in obesity and type 2 diabetes prevalence may inform interventions to reduce health inequities.
Exploring the genetic correlation between obesity-related traits and regional brain volumes: Evidence from UK Biobank cohort.
OBJECTIVE:To determine whether there is a correlation between obesity-related variants and regional brain volumes. METHODS:Based on a mixed linear model (MLM), we analyzed the association between 1,498 obesity-related SNPs in the GWAS Catalog and 164 regional brain volumes from 29,420 participants (discovery cohort N = 19,997, validation cohort N = 9,423) in UK Biobank. The statistically significant brain regions in association analysis were classified into 6 major neural networks (dopamine (DA) motive system, central autonomic network (CAN), cognitive emotion regulation, visual object recognition network, auditory object recognition network, and sensorimotor system). We summarized the association between obesity-related variants (metabolically healthy obesity variants, metabolically unhealthy obesity variants, and unclassified obesity-related variants) and neural networks. RESULTS:From association analysis, we determined that 17 obesity-related SNPs were associated with 51 regional brain volumes. Several single SNPs (e.g., rs13107325-T (SLC39A8), rs1876829-C (CRHR1), and rs1538170-T (CENPW)) were associated with multiple regional brain volumes. In addition, several single brain regions (e.g., the white matter, the grey matter in the putamen, subcallosal cortex, and insular cortex) were associated with multiple obesity-related variants. The metabolically healthy obesity variants were mainly associated with the regional brain volumes in the DA motive system, sensorimotor system and cognitive emotion regulation neural networks, while metabolically unhealthy obesity variants were mainly associated with regional brain volumes in the CAN and total tissue volumes. In addition, unclassified obesity-related variants were mainly associated with auditory object recognition network and total tissue volumes. The results of MeSH (medical subject headings) enrichment analysis showed that obesity genes associated with brain structure pointed to the functional relatedness with 5-Hydroxytryptamine receptor 4 (5-HT4), growth differentiation factor 5 (GDF5), and high mobility group protein AT-hook 2 (HMGA2 protein). CONCLUSION:In summary, we found that obesity-related variants were associated with different brain volume measures. On the basis of the multiple SNPs, we found that metabolically healthy and unhealthy obesity-related SNPs were associated with different brain neural networks. Based on our enrichment analysis, modifications of the 5-HT4 pathway might be a promising therapeutic strategy for obesity.
Shared familial risk factors between autism spectrum disorder and obesity - a register-based familial coaggregation cohort study.
Journal of child psychology and psychiatry, and allied disciplines
BACKGROUND:Meta-analyses suggest an association between autism spectrum disorder (ASD) and obesity, but the factors underlying this association remain unclear. This study investigated the association between ASD and obesity stratified on intellectual disability (ID). In addition, in order to gain insight into possible shared etiological factors, the potential role of shared familial liability was examined. METHOD:We studied a cohort of 3,141,696 individuals by linking several Swedish nationwide registers. We identified 35,461 individuals with ASD and 61,784 individuals with obesity. Logistic regression models were used to estimate the association between ASD and obesity separately by ID and sex and by adjusting for parental education, psychiatric comorbidity, and psychotropic medication. Potential shared familial etiologic factors were examined by comparing the risk of obesity in full siblings, maternal and paternal half-siblings, and full- and half-cousins of individuals with ASD to the risk of obesity in relatives of individuals without ASD. RESULTS:Individuals with ASD + ID (OR = 3.76 [95% CI, 3.38-4.19]) and ASD-ID (OR = 3.40 [95% CI, 3.23-3.58]) had an increased risk for obesity compared with individuals without ASD. The associations remained statistically significant when adjusting for parental education, psychiatric comorbidity, and medication. Sex-stratified analyses indicated a higher relative risk for males compared with females, with statistically significant interaction effects for ASD-ID, but not for ASD+ID in the fully adjusted model. First-degree relatives of individuals with ASD+ID and ASD-ID had an increased risk of obesity compared with first-degree relatives of individuals without ASD. The obesity risk was similar in second-degree relatives of individuals with ASD+ID but was lower for and ASD-ID. Full cousins of individuals with ASD+ID had a higher risk compared with half-cousins of individuals with ASD+ID). A similar difference in the obesity risk between full cousins and half-cousins was observed for ASD-ID. CONCLUSIONS:Individuals with ASD and their relatives are at increased risk for obesity. The risk might be somewhat higher for males than females. This warrants further studies examining potential common pleiotropic genetic factors and shared family-wide environmental factors for ASD and obesity. Such research might aid in identifying specific risks and underlying mechanisms in common between ASD and obesity.
Meta-Inflammation and Metabolic Reprogramming of Macrophages in Diabetes and Obesity: The Importance of Metabolites.
Russo Sara,Kwiatkowski Marcel,Govorukhina Natalia,Bischoff Rainer,Melgert Barbro N
Frontiers in immunology
Diabetes mellitus type II and obesity are two important causes of death in modern society. They are characterized by low-grade chronic inflammation and metabolic dysfunction (meta-inflammation), which is observed in all tissues involved in energy homeostasis. A substantial body of evidence has established an important role for macrophages in these tissues during the development of diabetes mellitus type II and obesity. Macrophages can activate into specialized subsets by cues from their microenvironment to handle a variety of tasks. Many different subsets have been described and in diabetes/obesity literature two main classifications are widely used that are also defined by differential metabolic reprogramming taking place to fuel their main functions. Classically activated, pro-inflammatory macrophages (often referred to as M1) favor glycolysis, produce lactate instead of metabolizing pyruvate to acetyl-CoA, and have a tricarboxylic acid cycle that is interrupted at two points. Alternatively activated macrophages (often referred to as M2) mainly use beta-oxidation of fatty acids and oxidative phosphorylation to create energy-rich molecules such as ATP and are involved in tissue repair and downregulation of inflammation. Since diabetes type II and obesity are characterized by metabolic alterations at the organism level, these alterations may also induce changes in macrophage metabolism resulting in unique macrophage activation patterns in diabetes and obesity. This review describes the interactions between metabolic reprogramming of macrophages and conditions of metabolic dysfunction like diabetes and obesity. We also focus on different possibilities of measuring a range of metabolites intra-and extracellularly in a precise and comprehensive manner to better identify the subsets of polarized macrophages that are unique to diabetes and obesity. Advantages and disadvantages of the currently most widely used metabolite analysis approaches are highlighted. We further describe how their combined use may serve to provide a comprehensive overview of the metabolic changes that take place intracellularly during macrophage activation in conditions like diabetes and obesity.
Obesity Is Associated With Increased Susceptibility to Influenza A (H1N1pdm) but Not H3N2 Infection.
Maier Hannah E,Kuan Guillermina,Gresh Lionel,Lopez Roger,Sanchez Nery,Schiller Amy,Ojeda Sergio,Harris Eva,Balmaseda Angel,Gordon Aubree
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
BACKGROUND:Obesity has been shown to increase the risk of severe outcomes and death for influenza virus infections. However, we do not understand the influence of obesity on susceptibility to infection or on nonsevere influenza outcomes. METHODS:We performed a case-ascertained, community-based study of influenza transmission within households in Nicaragua. To investigate whether obesity increases the likelihood of influenza infection and symptomatic infection we used logistic regression models. RESULTS:Between 2015 and 2018, a total of 335 index cases with influenza A and 1506 of their household contacts were enrolled. Obesity was associated with increased susceptibility to symptomatic H1N1pdm infection among adults (odds ratio [OR], 2.10; 95% confidence interval [CI], 1.08-4.06) but not children, and this association increased with age. Among adults with H1N1pdm infection, obesity was associated with increased likelihood of symptoms (OR, 3.91; 95% CI, 1.55-9.87). For middle-aged and older adults with obesity there was also a slight increase in susceptibility to any H1N1pdm infection (OR, 1.20; 95% CI, .62-2.34). Body mass index (BMI) was also linearly associated with increased susceptibility to symptomatic H1N1pdm infection, primarily among middle-aged and older women (5-unit BMI increase OR, 1.40; 95% CI, 1.00-1.97). Obesity was not associated with increased H3N2 susceptibility or associated symptoms. CONCLUSIONS:We found that, among adults, obesity is associated with susceptibility to H1N1pdm infection and with symptoms associated with H1N1pdm infection, but not with susceptibility to H3N2 infection or associated symptoms. These findings will help target prevention efforts and therapeutics to this high-risk population.
Cardiopulmonary coupling and serum cardiac biomarkers in obesity hypoventilation syndrome and obstructive sleep apnea with morbid obesity.
Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine
STUDY OBJECTIVES:The main cause of death in patients with obesity hypoventilation syndrome (OHS) is cardiac rather than respiratory failure. Here, we investigated autonomic-respiratory coupling and serum cardiac biomarkers in patients with OHS and obstructive sleep apnea (OSA) with comparable body mass index and apnea-hypopnea index. METHODS:Cardiopulmonary coupling (CPC) and cyclic variation of heart rate analysis was performed on the electrocardiogram signal from the overnight polysomnogram. Cardiac serum biomarkers were obtained in patients with OHS and OSA with a body mass index > 40 kg/m. Samples were obtained at baseline and after 3 months of positive airway pressure (PAP) therapy in both groups. RESULTS:Patients with OHS (n = 15) and OSA (n = 36) were recruited. No group differences in CPC, cyclic variation of heart rate, and serum biomarkers were observed at baseline and after 3 months of PAP therapy. An improvement in several CPC metrics, including the sleep apnea index, unstable sleep (low-frequency coupling and elevated low-frequency coupling narrow band), and cyclic variation of heart rate were observed in both groups with PAP use. However, distinct differences in response characteristics were noted. Elevated low-frequency coupling narrow band coupling correlated with highly sensitive troponin-T ( < .05) in the combined cohort. Baseline highly sensitive troponin-T inversely correlated with awake oxygen saturation in the OHS group ( < .05). CONCLUSIONS:PAP therapy can significantly improve CPC stability in patients with obesity with OSA or OHS, with key differences. Elevated low-frequency coupling narrow band may function as a surrogate biomarker for early subclinical cardiac disease. Low awake oxygen saturation could also increase this biomarker in OHS. CLINICAL TRIAL REGISTRATION:Registry: Australian New Zealand Clinical Trials Registry; Name: Obesity Hypoventilation Syndrome and Neurocognitive Dysfunction; URL: https://anzctr.org.au/Trial/Registration/TrialReview.aspx?id=367492; Identifier: ACTRN12615000122550. CITATION:Sivam S, Wang D, Wong KKH, et al. Cardiopulmonary coupling and serum cardiac biomarkers in obesity hypoventilation syndrome and obstructive sleep apnea with morbid obesity. . 2022;18(4):1063-1071.
Neonatal Anthropometrics and Obesity Treatment Response in Children and Adolescents.
The Journal of pediatrics
OBJECTIVE:To investigate the relationship between in utero growth conditions, as indicated by neonatal anthropometric measures, and childhood obesity treatment response, to examine the potential usefulness of neonatal anthropometrics as a potential childhood obesity treatment stratification tool. STUDY DESIGN:The study included 2474 children and adolescents with obesity (mean age, 11.2 years; range, 5.0-18.9 years) treated at the Children's Obesity Clinic in Holbæk, Denmark. Treatment response was registered prospectively, and neonatal data were collected from national electronic registers. RESULTS:Birth weight, birth length, birth weight for gestational age, and large for gestational age status were positively associated with the degree of obesity at treatment initiation. After a mean (SD) of 1.27 (0.69) years of enrollment in obesity treatment, the children exhibited a mean reduction of -0.32 (0.50) in body mass index SD score. No significant associations between neonatal anthropometric measures and childhood obesity treatment response were detected. CONCLUSIONS:Neonatal anthropometric measures were positively associated with the degree of obesity at treatment initiation but not with response to multidisciplinary treatment of childhood obesity. Individualization of obesity treatment based on neonatal anthropometry does not seem warranted.
Obesity and prostate cancer: A narrative review.
Wilson Rebekah L,Taaffe Dennis R,Newton Robert U,Hart Nicolas H,Lyons-Wall Philippa,Galvão Daniel A
Critical reviews in oncology/hematology
Overweight and obese men with prostate cancer are at an increased risk of disease recurrence, exacerbated treatment-related adverse effects, development of obesity-related comorbidities, earlier progression and development of metastatic disease, and higher all-cause and prostate cancer-specific mortality. The physiological mechanisms associating obesity with poor prostate cancer outcomes remain largely unknown; however, an increased inflammatory environment and metabolic irregularities associated with excess fat mass are commonly postulated. Although research is limited, fat loss strategies using exercise and nutrition programmes may slow down prostate cancer progression and improve a patient's prognosis. This review is an overview of: 1) the association between obesity and poor prostate cancer prognosis; 2) potential physiological mechanisms linking obesity and prostate cancer progression; 3) the effect of obesity on treatments for prostate cancer; and 4) the potential for weight loss strategies to improve outcomes in patients with prostate cancer.
Illness perceptions and health-related quality of life in individuals with overweight and obesity.
International journal of obesity (2005)
INTRODUCTION:To understand how individuals (self-)manage obesity, insight is needed into how patients perceive their condition and how this perception translates into health outcomes (e.g., health-related quality of life, HRQOL). Our objectives were (1) to examine illness perceptions in individuals with overweight and obesity, and (2) to investigate associations of these perceptions with physical and mental HRQOL. METHODS:In a cross-sectional analysis of the Netherlands Epidemiology of Obesity Study (n = 6432; 52% women), illness perceptions were assessed using the Brief Illness Perception Questionnaire, and HRQOL was assessed using the 36-Item Short-Form Health Survey. Illness perceptions were calculated for different categories of overall, abdominal, and metabolically unhealthy obesity. We investigated associations of illness perceptions with HRQOL using BMI-stratified multivariable linear regression analyses. RESULTS:Compared to individuals with normal weight, individuals with obesity believed to a higher extent that their condition had more serious consequences [Mean Difference (95%CI): 1.8 (1.6-2.0)], persisted for a longer time [3.4 (3.2-3.6)], manifested in more symptoms [3.8 (3.6-4.0)], caused more worry [4.2 (3.9-4.4)] and emotional distress [2.0 (1.8-2.2)], but was more manageable with medical treatment [3.1 (2.9-3.4)]. They perceived to a lesser extent that they had personal control [-2.2 (-2.4, -2.0)] and understanding [-0.3 (-0.5, -0.1)] regarding their condition. These negative perceptions were less pronounced in individuals with abdominal obesity. Behaviour/Lifestyle was attributed by 73% of participants to be the cause of their obesity. Stronger negative illness perceptions were associated with impaired HRQOL, particularly the physical component. CONCLUSION:Individuals with obesity perceived their conditions as threatening, and this seemed somewhat stronger in individuals with overall obesity than those with abdominal obesity. Behaviour/Lifestyle is a crucial target intervention and empowering self-management behaviour to achieve a healthy body weight may deliver promising results. In addition, strategies that aim to change negative perceptions of obesity into more adaptive ones may improve HRQOL.
Methodology and implementation of the WHO European Childhood Obesity Surveillance Initiative (COSI).
Breda João,McColl Karen,Buoncristiano Marta,Williams Julianne,Abdrakhmanova Shynar,Abdurrahmonova Zulfiya,Ahrens Wolfgang,Akhmedova Dilorom,Bakacs Márta,Boer Jolanda M A,Boymatova Khadichamo,Brinduse Lacramioara Aurelia,Cucu Alexandra,Duleva Vesselka,Endevelt Ronit,Sant'Angelo Victoria Farrugia,Fijałkowska Anna,Hadžiomeragić Aida Filipović,García-Solano Marta,Grøholt Else Karin,Gualtieri Andrea,Hassapidou Maria,Hejgaard Tatjana,Hyska Jolanda,Kelleher Cecily C,Kujundžić Enisa,Mäki Päivi,Markidou Ioannidou Eliza,Melkumova Marina,Moyersoen Isabelle,Milanović Sanja Musić,Nurk Eha,Ostojic Sergej M,Peterkova Valentina,Petrauskienė Aušra,Pudule Iveta,Rito Ana Isabel,Russell Jonsson Kenisha,Rutter Harry,Salanave Benoît,Seyidov Nabil,Shengelia Lela,Silitrari Natalia,Spinelli Angela,Spiroski Igor,Starc Gregor,Stojisavljević Dragana,Tanrygulyyeva Maya,Tichá Ľubica,Usupova Zhamilya,Weghuber Daniel,Yardim Nazan,Zamrazilová Hana,Zbanatskyi Vladyslav,Branca Francesco,Weber Martin,Rakovac Ivo
Obesity reviews : an official journal of the International Association for the Study of Obesity
Establishment of the WHO European Childhood Obesity Surveillance Initiative (COSI) has resulted in a surveillance system which provides regular, reliable, timely, and accurate data on children's weight status-through standardized measurement of bodyweight and height-in the WHO European Region. Additional data on dietary intake, physical activity, sedentary behavior, family background, and school environments are collected in several countries. In total, 45 countries in the European Region have participated in COSI. The first five data collection rounds, between 2007 and 2021, yielded measured anthropometric data on over 1.3 million children. In COSI, data are collected according to a common protocol, using standardized instruments and procedures. The systematic collection and analysis of these data enables intercountry comparisons and reveals differences in the prevalence of childhood thinness, overweight, normal weight, and obesity between and within populations. Furthermore, it facilitates investigation of the relationship between overweight, obesity, and potential risk or protective factors and improves the understanding of the development of overweight and obesity in European primary-school children in order to support appropriate and effective policy responses.
Childhood overweight and obesity abatement policies in Europe.
Wickramasinghe Kremlin,Chatterjee Saion,Williams Julianne,Weber Martin W,Rito Ana Isabel,Rippin Holly,Breda João
Obesity reviews : an official journal of the International Association for the Study of Obesity
Over the past two decades, a concerted effort to combat the rising tide of childhood overweight and obesity has taken shape. The World Health Organization (WHO) Commission on Ending Childhood Obesity (ECHO) provides recommendations for six priority areas of action, including the promotion of healthy food consumption, promotion of physical activity, preconception and pregnancy care, early childhood diet and physical activity, healthy nutrition and physical activity for school-aged children, and community-based weight management. This paper provides a snapshot of policies and measures aligned to these areas of action within the WHO European Region in order to encourage other countries to make similar efforts. Examples are drawn from Portugal (sugar-sweetened beverage tax, integrated nutrition strategy), the United Kingdom (soft drink levy, active commuting programs, urban design principles), Lithuania (prohibition of energy drinks), Norway (industry and government partnerships to promote healthier foods, nutrition education curriculum for schools), Hungary (tax subsidies to promote healthy diets), the European Union (cross-border marketing regulations, preconception and pregnancy care), Slovenia (food marketing restrictions), Spain (marketing restrictions within educational settings), Poland (investing in sports infrastructure), Russia (increasing sports participation), Estonia (redevelopment of the physical education curriculum), Netherlands (preconception and pregnancy care), Croatia (conditions to support breastfeeding), Austria (perinatal and early childhood nutrition), Czechia (life-course strategy), San Marino (nutrition and physical activity for school-aged children), Ukraine (potable water for schools), Ireland and Italy (community-based weight management approaches). Our findings suggest that a large disparity exists among the type and breadth of policies adopted by Member States, with a mix of single-issue policy responses and more cohesive strategies. The role of data, implementation research, and ongoing surveillance of country-level progress related to childhood overweight and obesity policies are discussed as an essential part of the iterative process of policy development. Additional work to systematically gather context-specific information on policy development, implementation, and reach according to ECHO's six areas of action by WHO European Region countries will inform future policy paradigms within the region.
The Association between Dietary Inflammatory Index and Sex Hormones among Men in the United States.
Zhang Chichen,Bian Haiyang,Chen Zeyu,Tian Bowen,Wang Haoyuan,Tu Xiang,Cai Boyu,Jin Kun,Zheng Xiaonan,Yang Lu,Qiu Shi
The Journal of urology
PURPOSE:This study investigated the association between Dietary Inflammatory Index and sex hormones in a large, nationally representative adult male sample. MATERIALS AND METHODS:We utilized data from the 2013-2014 and 2015-2016 National Health and Nutrition Examination Survey. Males aged ≥20 years who provided a 24-hour dietary intake history and underwent serum sex hormone testing were included in analysis. Weighted proportions and multivariable analysis controlling for age, race, energy, smoking status, education level, body mass index and time of venipuncture were used to evaluate the associations between Dietary Inflammatory Index and sex hormones. RESULTS:For 4,151 participants, Dietary Inflammatory Index ranged from -5.05 to 5.48. Mean±SD total testosterone was 419.30±176.27 ng/dl. Mean±SD total testosterone was lower among men in the highest tertile compared with men in the lowest tertile group (410.42±171.97 vs 422.71±175.69, p <0.001). A per unit increase in Dietary Inflammatory Index was related to 4.0% (95% CI 0.5-7.6) higher odds of testosterone deficiency. In the fully adjusted multivariable model, males in Dietary Inflammatory Index tertile 3 (the most pro-inflammatory) had 29.6% (3.1-63.0) higher odds of testosterone deficiency than those in tertile 1 (p trend=0.025). Interaction tests revealed no significant effect of body mass index on the association of Dietary Inflammatory Index with testosterone deficiency and all sex hormone parameters. CONCLUSIONS:Men adhering to a more pro-inflammatory diet appear to have a higher risk of testosterone deficiency, indicating the important role of diet in male reproductive health.
Life-Time Environmental Chemical Exposure and Obesity: Review of Epidemiological Studies Using Human Biomonitoring Methods.
Mohanto Nayan Chandra,Ito Yuki,Kato Sayaka,Kamijima Michihiro
Frontiers in endocrinology
The exponential global increase in the incidence of obesity may be partly attributable to environmental chemical (EC) exposure. Humans are constantly exposed to ECs, primarily through environmental components. This review compiled human epidemiological study findings of associations between blood and/or urinary exposure levels of ECs and anthropometric overweight and obesity indices. The findings reveal research gaps that should be addressed. We searched MEDLINE (PubMed) for full text English articles published in 2006-2020 using the keywords "environmental exposure" and "obesity". A total of 821 articles were retrieved; 102 reported relationships between environmental exposure and obesity indices. ECs were the predominantly studied environmental exposure compounds. The ECs were grouped into phenols, phthalates, and persistent organic pollutants (POPs) to evaluate obesogenic roles. In total, 106 articles meeting the inclusion criteria were summarized after an additional search by each group of EC combined with obesity in the PubMed and Scopus databases. Dose-dependent positive associations between bisphenol A (BPA) and various obesity indices were revealed. Both individual and summed di(2-ethylhexyl) phthalate (DEHP) and non-DEHP metabolites showed inconsistent associations with overweight and obesity indices, although mono-butyl phthalate (MBP), mono-ethyl phthalate (MEP), and mono-benzyl phthalate (MBzP) seem to have obesogenic roles in adolescents, adults, and the elderly. Maternal exposure levels of individual POP metabolites or congeners showed inconsistent associations, whereas dichlorodiphenyldichloroethylene (DDE) and perfluorooctanoic acid (PFOA) were positively associated with obesity indices. There was insufficient evidence of associations between early childhood EC exposure and the subsequent development of overweight and obesity in late childhood. Overall, human evidence explicitly reveals the consistent obesogenic roles of BPA, DDE, and PFOA, but inconsistent roles of phthalate metabolites and other POPs. Further prospective studies may yield deeper insights into the overall scenario.
A Neuroeconomics Approach to Obesity.
Obesity is a heterogeneous condition that is affected by physiological, behavioral, and environmental factors. Value-based decision making is a useful framework for integrating these factors at the individual level. The disciplines of behavioral economics and reinforcement learning provide tools for identifying specific cognitive and motivational processes that may contribute to the development and maintenance of obesity. Neuroeconomics complements these disciplines by studying the neural mechanisms underlying these processes. We surveyed recent literature on individual decision characteristics that are most frequently implicated in obesity: discounting the value of future outcomes, attitudes toward uncertainty, and learning from rewards and punishments. Our survey highlighted both consistent and inconsistent behavioral findings. These findings underscore the need to examine multiple processes within individuals to identify unique behavioral profiles associated with obesity. Such individual characterization will inform future studies on the neurobiology of obesity as well as the design of effective interventions that are individually tailored.
Investigating obesity-related risk factors for childhood asthma.
Chen Yang-Ching,Su Ming-Wei,Brumpton Ben M,Lee Yungling L
Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology
BACKGROUND:We tested the hypothesis that multiple obesity-related risk factors (obesity, physical activity, cardiopulmonary physical fitness, sleep-disorder breathing (SDB), and sleep quality) are associated with childhood asthma using a Mendelian randomization (MR) design. Furthermore, we aim to investigate whether these risk factors were associated with incident asthma prospectively. METHODS:In total, 7069 children aged 12 from the Taiwan Children Health Study were enrolled in the current study. Cross-sectional logistic regression, one-sample MR, summary-level MR sensitivity analyses, and prospective survival analyses were used to investigate each causal pathway. RESULTS:In MR analysis, three of the five risk factors (obesity, SDB, and sleep quality) were associated with asthma, with the highest effect sizes per inter-quartile range (IQR) increase observed for sleep quality (odds ratio [OR] = 1.42; 95% confidence interval [CI]: 1.06 to 1.92) and the lowest for obesity (OR = 1.08; 95% CI: 1.00-1.16). In the prospective survival analysis, obesity showed the highest risk of incident asthma per IQR increase (hazard ratio [HR] = 1.28; 95% CI: 1.05 to 1.56), followed by SDB (HR = 1.18; 95% CI: 1.08 to 1.29) and sleep quality (HR = 1.10; 95% CI: 1.03 to 1.17). CONCLUSION:Among the examined factors, the most plausible risk factors for asthma were obesity, SDB, and poor sleep quality. For the prevention of childhood asthma, relevant stakeholders should prioritize improving children's sleep quality and preventing obesity comorbidities such as SDB.
Obesity and pregnancy, the perfect metabolic storm.
European journal of clinical nutrition
Pregnancy is a physiological stress that requires dynamic, regulated changes affecting maternal and fetal adiposity. Excessive accumulation of dysfunctional adipose tissue defined by metabolic and molecular alterations cause severe health consequences for mother and fetus. When subjected to sustained overnutrition, the cellular and lipid composition of the adipose tissue changes predisposing to insulin resistance, diabetes, and other metabolic disorders compromising the outcome of the pregnancy. Moreover, excessive maternal weight gain, usually in the context of obesity, predisposes to an increased flux of nutrients from mother to fetus throughout the placenta. The fetus of an obese mother will accumulate more adiposity and may increase the risk of future metabolic disorder later in life. Thus, further understanding of the interaction between maternal metabolism, epigenetic regulation of the adipose tissue, and their transgenerational transfer are required to mitigate the adverse health outcomes for the mother and the fetus associated with maternal obesity.
Diet and Obesity-Induced Methylglyoxal Production and Links to Metabolic Disease.
Hernandez-Castillo Carlos,Shuck Sarah C
Chemical research in toxicology
The obesity rate in the United States is 42.4% and has become a national epidemic. Obesity is a complex condition that is influenced by socioeconomic status, ethnicity, genetics, age, and diet. Increased consumption of a Western diet, one that is high in processed foods, red meat, and sugar content, is associated with elevated obesity rates. Factors that increase obesity risk, such as socioeconomic status, also increase consumption of a Western diet because of a limited access to healthier options and greater affordability of processed foods. Obesity is a public health threat because it increases the risk of several pathologies, including atherosclerosis, diabetes, and cancer. The molecular mechanisms linking obesity to disease onset and progression are not well understood, but a proposed mechanism is physiological changes caused by altered lipid peroxidation, glycolysis, and protein metabolism. These metabolic pathways give rise to reactive molecules such as the abundant electrophile methylglyoxal (MG), which covalently modifies nucleic acids and proteins. MG-adducts are associated with obesity-linked pathologies and may have potential for biomonitoring to determine the risk of disease onset and progression. MG-adducts may also play a role in disease progression because they are mutagenic and directly impact protein stability and function. In this review, we discuss how obesity drives metabolic alterations, how these alterations lead to MG production, the association of MG-adducts with disease, and the potential impact of MG-adducts on cellular function.
Impact of Obesity on Heart Transplantation Outcomes.
Journal of the American Heart Association
Background Patients with obesity and advanced heart failure face unique challenges on the path to heart transplantation. There are limited data on waitlist and transplantation outcomes in this population. We aimed to evaluate the impact of obesity on heart transplantation outcomes, and to investigate the effects of the new organ procurement and transplantation network allocation system in this population. Methods and Results This cohort study of adult patients listed for heart transplant used the United Network for Organ Sharing database from January 2006 to June 2020. Patients were stratified by body mass index (BMI) (18.5-24.9, 25-29.9, 30-34.9, 35-39.9, and 40-55 kg/m). Recipient characteristics and donor characteristics were analyzed. Outcomes analyzed included transplantation, waitlist death, and posttransplant death. BMI 18.5 to 24.9 kg/m was used as the reference compared with progressive BMI categories. There were 46 645 patients listed for transplantation. Patients in higher BMI categories were less likely to be transplanted. The lowest likelihood of transplantation was in the highest BMI category, 40 to 55 kg/m (hazard ratio [HR], 0.19 [0.05-0.76]; =0.02). Patients within the 2 highest BMI categories had higher risk of posttransplantation death (HR, 1.29; <0.001 and HR, 1.65; <0.001, respectively). Left ventricular assist devices among patients in obese BMI categories decreased after the allocation system change (<0.001, all). After the change, patients with obesity were more likely to undergo transplantation (BMI 30-35 kg/m: HR, 1.31 [1.18-1.46], <0.001; BMI 35-55 kg/m: HR, 1.29 [1.06-1.58]; =0.01). Conclusions There was an inverse relationship between BMI and likelihood of heart transplantation. Higher BMI was associated with increased risk of posttransplant mortality. Patients with obesity were more likely to undergo transplantation under the revised allocation system.
Overweight and obesity in pregnancy: their impact on epigenetics.
European journal of clinical nutrition
Over the last few decades, the prevalence of obesity has risen to epidemic proportions worldwide. Consequently, the number of obesity in pregnancy has risen drastically. Gestational overweight and obesity are associated with impaired outcomes for mother and child. Furthermore, studies show that maternal obesity can lead to long-term consequences in the offspring, increasing the risk for obesity and cardiometabolic disease in later life. In addition to genetic mechanisms, mounting evidence demonstrates the induction of epigenetic alterations by maternal obesity, which can affect the offspring's phenotype, thereby influencing the later risk of obesity and cardiometabolic disease. Clear evidence in this regard comes from various animal models of maternal obesity. Evidence derived from clinical studies remains limited. The current article gives an overview of pathophysiological changes associated with maternal obesity and their consequences on placental structure and function. Furthermore, a short excurse is given on epigenetic mechanisms and emerging data regarding a putative interaction between metabolism and epigenetics. Finally, a summary of important findings of animal and clinical studies investigating maternal obesity-related epigenetic effects is presented also addressing current limitations of clinical studies.
Effect of low-calorie versus low-carbohydrate ketogenic diet in type 2 diabetes.
Hussain Talib A,Mathew Thazhumpal C,Dashti Ali A,Asfar Sami,Al-Zaid Naji,Dashti Hussein M
Nutrition (Burbank, Los Angeles County, Calif.)
OBJECTIVE:Effective diabetic management requires reasonable weight control. Previous studies from our laboratory have shown the beneficial effects of a low-carbohydrate ketogenic diet (LCKD) in patients with type 2 diabetes after its long term administration. Furthermore, it favorably alters the cardiac risk factors even in hyperlipidemic obese subjects. These studies have indicated that, in addition to decreasing body weight and improving glycemia, LCKD can be effective in decreasing antidiabetic medication dosage. Similar to the LCKD, the conventional low-calorie, high nutritional value diet is also used for weight loss. The purpose of this study was to understand the beneficial effects of LCKD compared with the low-calorie diet (LCD) in improving glycemia. METHODS:Three hundred and sixty-three overweight and obese participants were recruited from the Al-Shaab Clinic for a 24-wk diet intervention trial; 102 of them had type 2 diabetes. The participants were advised to choose LCD or LDKD, depending on their preference. Body weight, body mass index, changes in waist circumference, blood glucose level, changes in hemoglobin and glycosylated hemoglobin, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, uric acid, urea and creatinine were determined before and at 4, 8, 12, 16, 20, and 24 wk after the administration of the LCD or LCKD. The initial dose of some antidiabetic medications was decreased to half and some were discontinued at the beginning of the dietary program in the LCKD group. Dietary counseling and further medication adjustment were done on a biweekly basis. RESULTS:The LCD and LCKD had beneficial effects on all the parameters examined. Interestingly, these changes were more significant in subjects who were on the LCKD as compared with those on the LCD. Changes in the level of creatinine were not statistically significant. CONCLUSION:This study shows the beneficial effects of a ketogenic diet over the conventional LCD in obese diabetic subjects. The ketogenic diet appears to improve glycemic control. Therefore, diabetic patients on a ketogenic diet should be under strict medical supervision because the LCKD can significantly lower blood glucose levels.
A comprehensive review of the impact of obesity on plasma cell disorders.
Multiple myeloma (MM) remains an incurable plasma cell malignancy. Although little is known about the etiology of MM, several metabolic risk factors such as obesity, diabetes, poor nutrition, many of which are modifiable, have been linked to the pathogenesis of numerous neoplasms including MM. In this article, we provide a detailed summary of what is known about the impact of obesity on the pathogenesis of MM, its influence on outcomes in MM patients, and discuss potential mechanisms through which obesity is postulated to influence MM risk and prognosis. Along with advancements in treatment modalities to improve survival in MM patients, focused efforts are needed to prevent or intercept MM at its earliest stages. The consolidated findings presented in this review highlight the need for clinical trials to assess if lifestyle modifications can reduce the incidence and improve outcomes of MM in high-risk populations. Data generated from such studies can help formulate evidence-based lifestyle recommendations for the prevention and control of MM.
Thyroid cancers potentially preventable by reducing overweight and obesity in Australia: A pooled cohort study.
Laaksonen Maarit A,MacInnis Robert J,Canfell Karen,Shaw Jonathan E,Magliano Dianna J,Banks Emily,Giles Graham G,Byles Julie E,Gill Tiffany K,Mitchell Paul,Hirani Vasant,Cumming Robert G,Vajdic Claire M
International journal of cancer
Thyroid cancer incidence and the prevalence of overweight and obesity are increasing, but the future thyroid cancer burden attributable to contemporary levels of overweight and obesity has not been evaluated before. We quantified this burden in Australia, and assessed whether the overweight/obesity-attributable burden differed by sex or other population subgroupings. We estimated the strength of the associations of overweight and obesity with thyroid cancer with adjusted proportional hazards models using pooled data from seven Australian cohorts (N = 367 058) with 431 thyroid cancer cases ascertained from linked national cancer registry data during a maximum 22-year follow-up. We combined these estimates with nationally representative 2017 to 2018 estimates of overweight and obesity prevalence to estimate population attributable fractions (PAFs) of future thyroid cancers attributable to overweight and obesity, accounting for competing risk of death, and compared PAFs for population subgroups. Contemporary levels of overweight and obesity explain 18.6% (95% confidence interval [CI] = 5.2%-30.2%), and obesity alone 13.7% (95% CI: 5.2%-21.4%), of the future thyroid cancer burden. The obesity-attributable thyroid cancer burden is 21.4% (95% CI: 2.8%-36.5%) for men and 10.1% (95% CI: 0.8%-18.6%) for women. Were the currently obese overweight instead, 9.9% (95% CI: 1.0%-18.1%) of thyroid cancers could be avoided. The relative overweight/obesity-attributable burden is higher for those consuming on average more than two alcoholic drinks per day (63.4%) and for those who are not married/co-habiting (33.2%). In conclusion, avoiding excess weight, especially obesity, should be a priority for thyroid cancer prevention. Further studies, with findings stratified by tumour size, may reveal the potential role of overdiagnosis in our results.
IL-20 is involved in obesity by modulation of adipogenesis and macrophage dysregulation.
IL-20 is a proinflammatory cytokine of the IL-10 family and involved in several diseases. However, the regulatory role of IL-20 in obesity is not well understood. We explored the function of IL-20 in the pathogenesis of obesity-induced insulin resistance by ELISA, Western blotting and flow cytometry. The therapeutic potential of IL-20 monoclonal antibody 7E for ameliorating diet-induced obesity was analysed in murine models. Higher serum IL-20 levels were detected in obese patients. It was upregulated in leptin-deficient (ob/ob), leptin-resistant (db/db) and high-fat diet (HFD)-induced murine obesity models. In vitro, IL-20 regulated the adipocyte differentiation and the polarization of bone marrow-derived macrophages into proinflammatory M1 type. It also caused inflammation and macrophage retention in adipose tissues by upregulating TNF-α, monocyte chemotactic protein 1 (MCP-1), netrin 1 and unc5b (netrin receptor) expression in macrophages and netrin 1, leptin and MCP-1 in adipocytes. IL-20 promoted insulin resistance by inhibiting glucose uptake in mature adipocytes through the SOCS-3 pathway. In HFD-induced obesity in mice, 7E treatment reduced body weight and improved glucose tolerance and insulin sensitivity; it also reduced local inflammation and the number of M1-like macrophages in adipose tissues. We have identified a critical role of IL-20 in obesity-induced inflammation and insulin resistance, and we conclude that IL-20 may be a novel target for treating obesity and insulin resistance in patients with metabolic disorders.
The Role of Childhood Asthma in Obesity Development: A Nationwide US Multicohort Study.
Epidemiology (Cambridge, Mass.)
RATIONALE:Asthma and obesity often co-occur. It has been hypothesized that asthma may contribute to childhood obesity onset. OBJECTIVES:To determine if childhood asthma is associated with incident obesity and examine the role of asthma medication in this association. METHODS:We studied 8,716 children between ages 6 and 18.5 years who were nonobese at study entry participating in 18 US cohorts of the Environmental influences on Child Health Outcomes program (among 7,299 children with complete covariate data mean [SD] study entry age = 7.2 [1.6] years and follow up = 5.3 [3.1] years). MEASUREMENTS AND MAIN RESULTS:We defined asthma based on caregiver report of provider diagnosis. Incident obesity was defined as the first documented body mass index ≥95th percentile for age and sex following asthma status ascertainment. Over the study period, 26% of children had an asthma diagnosis and 11% developed obesity. Cox proportional hazards models with sex-specific baseline hazards were fitted to assess the association of asthma diagnosis with obesity incidence. Children with asthma had a 23% (95% confidence intervals [CI] = 4, 44) higher risk for subsequently developing obesity compared with those without asthma. A novel mediation analysis was also conducted to decompose the total asthma effect on obesity into pathways mediated and not mediated by asthma medication use. Use of asthma medication attenuated the total estimated effect of asthma on obesity by 64% (excess hazard ratios = 0.64; 95% CI = -1.05, -0.23). CONCLUSIONS:This nationwide study supports the hypothesis that childhood asthma is associated with later risk of obesity. Asthma medication may reduce this association and merits further investigation as a potential strategy for obesity prevention among children with asthma.
Roles of amino acid derivatives in the regulation of obesity.
Zheng Jie,Xiao Hao,Duan Yehui,Song Bo,Zheng Changbing,Guo Qiuping,Li Fengna,Li Tiejun
Food & function
Obesity is an issue of great concern to people all over the world. It is accompanied by serious complications, leading to reduced quality of life and higher morbidity and mortality. Over the past few years, there has been an explosion in knowledge about the roles of potential therapeutic agents in obesity management. Among them, amino acid (AA) derivatives, such as taurine, glutathione (GSH), betaine, α-ketoglutarate (AKG), β-aminoisobutyric acid (BAIBA), and β-hydroxy-β-methylbutyrate (HMB), have recently gained popularity due to their beneficial effects on the promotion of weight loss and improvement in the lipid profile. The mechanisms of action of these derivatives mainly include inhibiting adipogenesis, increasing lipolysis, promoting brown/beige adipose tissue (BAT) development, and improving glucose metabolism. Therefore, this review summarizes these AA derivatives and the possible mechanisms responsible for their anti-obesity effects. Based on the current findings, these AA derivatives could be potential therapeutic agents for obesity and its related metabolic diseases.
New Horizons: Is Obesity a Disorder of Neurotransmission?
Caron Alexandre,Jane Michael Natalie
The Journal of clinical endocrinology and metabolism
Obesity is a disease of the nervous system. While some will view this statement as provocative, others will take it as obvious. Whatever our side is, the pharmacology tells us that targeting the nervous system works for promoting weight loss. It works, but at what cost? Is the nervous system a safe target for sustainable treatment of obesity? What have we learned-and unlearned-about the central control of energy balance in the last few years? Herein we provide a thought-provoking exploration of obesity as a disorder of neurotransmission. We discuss the state of knowledge on the brain pathways regulating energy homeostasis that are commonly targeted in anti-obesity therapy and explore how medications affecting neurotransmission such as atypical antipsychotics, antidepressants, and antihistamines relate to body weight. Our goal is to provide the endocrine community with a conceptual framework that will help expending our understanding of the pathophysiology of obesity, a disease of the nervous system.
Dysfunctional Brain Reward System in Child Obesity.
Pujol Jesus,Blanco-Hinojo Laura,Martínez-Vilavella Gerard,Deus Joan,Pérez-Sola Víctor,Sunyer Jordi
Cerebral cortex (New York, N.Y. : 1991)
Eating habits leading to obesity may reflect nonhomeostatic behavior based on excessive immediate-reward seeking. However, it is currently unknown to what extent excess weight is associated with functional alterations in the brain's reward system in children. We tested the integrity of reward circuits using resting-state functional connectivity magnetic resonance imaging in a population of 230 children aged 8-12 years. The major components of the reward system were identified within the ventral striatum network defined on the basis of the nucleus accumbens connectivity pattern. The functional structure of the cerebral cortex was characterized using a combination of local functional connectivity measures. Higher body mass index was associated with weaker connectivity between the cortical and subcortical elements of the reward system, and enhanced the integration of the sensorimotor cortex to superior parietal areas relevant to body image formation. Obese children, unlike WHO-defined overweight condition, showed functional structure alterations in the orbitofrontal cortex and amygdala region similar to those previously observed in primary obsessive-compulsive disorder and Prader-Willi syndrome associated with obsessive eating behavior. Results further support the view that childhood obesity is not simply a deviant habit with restricted physical health consequences but is associated with reward system dysfunction characterizing behavioral control disorders.
COVID-19 vaccines are effective in people with obesity: A position statement from The Obesity Society.
Obesity (Silver Spring, Md.)
The position statement is issued by The Obesity Society in response to published literature, as well as inquiries made to the Society by patients, providers, Society members, policy makers, and others regarding the efficacy of vaccines in persons with obesity against SARS-CoV-2, the virus that causes COVID-19. The Obesity Society has critically evaluated data from published peer-reviewed literature and briefing documents from Emergency Use Authorization applications submitted by Pfizer-BioNTech, Moderna, and Johnson & Johnson. We conclude that these vaccines are highly efficacious, and their efficacy is not significantly different in people with and without obesity, based on scientific evidence available at the time of publication. The Obesity Society believes there is no definitive way to determine which of these three COVID-19 vaccines is "best" for any weight subpopulation (because of differences in the trial design and outcome measures in the phase 3 trials, elapsed time between doses, and regional differences in the presence of SARS-CoV-2 variants [e.g., South Africa B.1.351 in Johnson & Johnson trial]). All three trials have demonstrated high efficacy against COVID-19-associated hospitalization and death. Therefore, The Obesity Society encourages adults with obesity ≥18 years (≥16 years for Pfizer-BioNTech) to undergo vaccination with any one of the currently available vaccines authorized for emergency use by the US Food and Drug Administration as soon as they are able.
Obesity, metabolic syndrome, and inflammation: An update for anaesthetists caring for patients with obesity.
Eley Victoria A,Thuzar Moe,Navarro Séverine,Dodd Benjamin R,van Zundert André A
Anaesthesia, critical care & pain medicine
Our understanding of chronic inflammation in obesity is evolving. Suggested mechanisms include hypoxia of adipose tissue and a subsequent increase in circulating cytokines. It is now known that adipose tissue, far from being an inert tissue, produces and secretes multiple peptides that influence inflammation and metabolism, including substrates of the renin-angiotensin-aldosterone system (RAAS). RAAS blocking antihypertensive medication and cholesterol-lowering agents are now being evaluated for their metabolic and inflammation-modulating effects. Surgery also has pro-inflammatory effects, which may be exacerbated in patients with obesity. This narrative review will summarise the recent literature surrounding obesity, metabolic syndrome, inflammation, and interplay with the RAAS, with evidence-based recommendations for the optimisation of patients with obesity, prior to surgery and anaesthesia.
Social entrepreneurship in obesity prevention: A scoping review.
Obesity reviews : an official journal of the International Association for the Study of Obesity
We conducted a scoping review of social ventures in obesity and developed a taxonomy of their interventions and business models. Sources included PubMed, Business Source Premier, ABI Inform, Factiva, Google, Facebook, Twitter, social entrepreneurship networks (Ashoka, Skoll, and Schwab), and social entrepreneurship competitions. Our review identified 512 social ventures in 32 countries; 93% originated from developed countries. Their areas of intervention included diet and nutrition, urban farming, physical activity, access to healthy food, and health literacy. They addressed factors beyond health such as education, affordability, employment, and the built and natural environments. To support their programs of work, social ventures developed various business models with multiple revenue or resource streams. Social ventures designed double-duty interventions that were aligned with additional meaningful social or environmental objectives. This "bundling" of objectives allowed social ventures to appeal to a wider target audience. Most of the social ventures were initiated, supported, or sustained by local communities. Social ventures offer financially self-sufficient approaches to obesity reduction and could potentially relieve the burden on healthcare systems. Policymakers should consider social entrepreneurs as partners in obesity prevention.
A Twitter discourse analysis of negative feelings and stigma related to NAFLD, NASH and obesity.
Lazarus Jeffrey V,Kakalou Christine,Palayew Adam,Karamanidou Christina,Maramis Christos,Natsiavas Pantelis,Picchio Camila A,Villota-Rivas Marcela,Zelber-Sagi Shira,Carrieri Patrizia
Liver international : official journal of the International Association for the Study of the Liver
BACKGROUND:People with non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are stigmatized, partly since 'non-alcoholic' is in the name, but also because of obesity, which is a common condition in this group. Stigma is pervasive in social media and can contribute to poorer health outcomes. We examine how stigma and negative feelings concerning NAFLD/NASH and obesity manifest on Twitter. METHODS:Using a self-developed search terms index, we collected NAFLD/NASH tweets from May to October 2019 (Phase I). Because stigmatizing NAFLD/NASH tweets were limited, Phase II focused on obesity (November-December 2019). Via sentiment analysis, >5000 tweets were annotated as positive, neutral or negative and used to train machine learning-based Natural Language Processing software, applied to 193 747 randomly sampled tweets. All tweets collected were analysed. RESULTS:In Phase I, 16 835 tweets for NAFLD and 2376 for NASH were retrieved. Of the annotated NAFLD/NASH tweets, 97/1130 (8.6%) and 63/535 (11.8%), respectively, related to obesity and 13/1130 (1.2%) and 5/535 (0.9%), to stigma; they primarily focused on scientific discourse and unverified information. Of the 193 747 non-annotated obesity tweets (Phase II), the algorithm classified 40.0% as related to obesity, of which 85.2% were negative, 1.0% positive and 13.7% neutral. CONCLUSIONS:NAFLD/NASH tweets mostly indicated an unmet information need and showed no clear signs of stigma. However, the negative content of obesity tweets was recurrent. As obesity-related stigma is associated with reduced care engagement and lifestyle modification, the main NAFLD/NASH treatment, stigma-reducing interventions in social media should be included in the liver health agenda.
Variation in glucocorticoid sensitivity and the relation with obesity.
Obesity reviews : an official journal of the International Association for the Study of Obesity
Increasing evidence points to a relation between increased glucocorticoid (GC) exposure and weight gain. In support, long-term cortisol measurements using hair analysis revealed that many individuals with obesity appear to have cortisol values in the high physiological range. The mechanisms behind this relationship need to be determined in order to develop targeted therapy to reach sustainable weight loss in these subgroups. The effect of GCs is not only determined by the plasma concentration of GCs but also by individual differences in GC sensitivity and the target tissue, which can be analyzed by functional GC assays. GC sensitivity is influenced by multiple genetic and acquired (e.g., disease-related) factors, including intracellular GC availability, hormone binding affinity, and expression levels of the GC receptors and their isoforms, as well as factors involved in the modulation of gene transcription. Interindividual differences in GC sensitivity also play a role in the response to exogenous GCs, with respect to both therapeutic and adverse effects. Accordingly, in this review, we summarize current knowledge on mechanisms that influence GC sensitivity and their relationships with obesity and discuss personalized treatment options targeting the GC receptor.
Perinatal Polyunsaturated Fatty Acid Status and Obesity Risk.
Demmelmair Hans,Koletzko Berthold
High obesity rates in almost all regions of the world prompt an urgent need for effective obesity prevention. Very good scientific evidence from cell culture and rodent studies show that the availability of essential polyunsaturated fatty acids (PUFA) and their long-chain polyunsaturated derivatives, namely, arachidonic acid, eicosapentaenoic acid and docosahexaenoic acid, influence adipogenesis; for this reason, early life status may influence later obesity risk. The respective PUFA effects could be mediated via their eicosanoid derivatives, their influence on cell membrane properties, the browning of white adipose tissue, changes to the offspring gut microbiome, their influence on developing regulatory circuits, and gene expression during critical periods. Randomized clinical trials and observational studies show divergent findings in humans, with mostly null findings but also the positive and negative effects of an increased n-3 to n-6 PUFA ratio on BMI and fat mass development. Hence, animal study findings cannot be directly extrapolated to humans. Even though the mechanistic data basis for the effects of n-3 PUFA on obesity risk appears promising, no recommendations for humans can be derived at present.
Nuciferine, an active ingredient derived from lotus leaf, lights up the way for the potential treatment of obesity and obesity-related diseases.
Wan Yan,Xia Jia,Xu Jin-Feng,Chen Lu,Yang Yu,Wu Jiao-Jiao,Tang Fei,Ao Hui,Peng Cheng
Obesity, is an increasingly global public health problem associated complications. However, the proven anti-obesity agents are inefficient with adverse side effects; hence attention is being paid to novel drugs from natural resources to manage obesity and obesity-related diseases. Nuciferine (NF) is a high-quality aporphine alkaloid present in lotus leaf. Unlike the chemical drugs, NF elicits anti-obesity, anti-dyslipidemia, anti-hyperglycemic, anti-hypouricemic, anti-inflammatory, and anti-tumor effects, and affinity to neural receptors, and protection against obesity-related diseases. The underlying mechanism of NF includes the regulation of targeted molecules and pathways related to metabolism, inflammation, and cancer and modulation of Ca flux, gut microbiota, and ferroptosis. Besides, the clinical application, availability, pharmacokinetics, pharmaceutics, and security of NF have been established, highlighting the potential of developing NF as an anti-obesity agent. Therefore, this review provides a comprehensive summarization, which sheds light on future research in NF.
Imprinted lncRNA Dio3os preprograms intergenerational brown fat development and obesity resistance.
Maternal obesity (MO) predisposes offspring to obesity and metabolic disorders but little is known about the contribution of offspring brown adipose tissue (BAT). We find that MO impairs fetal BAT development, which persistently suppresses BAT thermogenesis and primes female offspring to metabolic dysfunction. In fetal BAT, MO enhances expression of Dio3, which encodes deiodinase 3 (D3) to catabolize triiodothyronine (T3), while a maternally imprinted long noncoding RNA, Dio3 antisense RNA (Dio3os), is inhibited, leading to intracellular T3 deficiency and suppression of BAT development. Gain and loss of function shows Dio3os reduces D3 content and enhances BAT thermogenesis, rendering female offspring resistant to high fat diet-induced obesity. Attributing to Dio3os inactivation, its promoter has higher DNA methylation in obese dam oocytes which persists in fetal and adult BAT, uncovering an oocyte origin of intergenerational obesity. Overall, our data uncover key features of Dio3os activation in BAT to prevent intergenerational obesity and metabolic dysfunctions.
An alternative approach to obesity treatment: intermittent fasting.
Overweight and obesity are an important public health problem that affects a significant part of the world population and increases the risk of many metabolic diseases. Weight loss is the primary goal in obesity treatment, and many different dietary interventions are tried for this purpose. Intermittent fasting is a diet that has become popular in recent years with the weight loss it provides and includes periods of fasting and feeding. In addition to providing weight loss, intermittent fasting also has positive effects on important risk factors such as glucoregulatory parameters, blood lipids, and oxidative stress. Intermittent fasting appears to be an effective and safe way to achieve weight loss in obesity. It could also have therapeutic effects on obesity-related diseases. The aim of this review was to bring together up-to-date information on the effects of intermittent fasting on obesity and various obesity-related diseases, mechanisms of action, possible benefits and harms, and potential uses.
Dietary supplements and alternative therapies for obesity: A Perspective from The Obesity Society's Clinical Committee.
Kidambi Srividya,Batsis John A,Donahoo William T,Jastreboff Ania M,Kahan Scott,Saunders Katherine H,Heymsfield Steven B
Obesity (Silver Spring, Md.)
In this Perspective Statement from The Obesity Society, the Clinical Committee discusses the use of weight loss supplements in the United States and the lack of regulatory oversight and rigorous testing of their efficacy and safety. A number of products and services claiming to promote weight loss are directly marketed to individuals with obesity and those wanting to lose weight. These products are not regulated as "drugs" by the Federal Drug Administration but, rather, are treated as dietary supplements if ingredients are "generally regarded as safe," requiring little or no testing to show efficacy or safety. Health care providers should be aware of the lack of evidence and deficiencies in regulatory oversight of dietary supplements marketed for weight loss. Regulatory authorities should protect consumers by ensuring accurate and safe marketing claims and preventing promotion of unproven and potentially unsafe products and claims.
Mechanisms by Which Obesity Promotes Acute Graft--Host Disease in Mice.
Frontiers in immunology
The efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) is limited by the occurrence of acute and chronic graft--host disease (GVHD). We have recently demonstrated that obesity results in exacerbated acute gastrointestinal GVHD in both mouse models and clinical outcomes due to increased pro-inflammatory cytokine responses and microbiota alterations. We therefore wanted to delineate the role of the various parameters in obesity, adiposity, effects of high-fat (HF) diet, and the role of microbiome on GVHD pathogenesis, by taking advantage of a mouse strain resistant to diet-induced obesity (DIO). Female BALB/c mice are resistant to DIO phenotype with approximately 50% becoming DIO under HF diets. The DIO-susceptible recipients rapidly succumb to acute gut GVHD, whereas the DIO-resistant recipient littermates, which do not become obese, are partially protected from GVHD, indicating that being on HF diet alone contributes to but is not the primary driver of GVHD. Microbiome assessment revealed restricted diversity in both cohorts of mice, but coprophagy normalizes the microbiota in mice housed together. We then individually housed DIO-resistant, DIO-susceptible, and lean control mice. Notably, each of the individually housed groups demonstrates marked restricted diversity that has been shown to occur from the stress of single housing. Despite the restricted microbiome diversity, the GVHD pathogenesis profile remains consistent in the group-housed mice, with the lean control single-housed mice exhibiting no acute GVHD and DIO-resistant recipients showing again partial protection. These results demonstrate that the deleterious effects of obesity on acute gut GVHD are critically dependent on adiposity with the HF diet also playing a lesser role, and the microbiome alterations with obesity instead appear to fuel ongoing acute GVHD processes.
TRPA1: Pharmacology, natural activators and role in obesity prevention.
Mahajan Neha,Khare Pragyanshu,Kondepudi Kanthi Kiran,Bishnoi Mahendra
European journal of pharmacology
Transient receptor potential ankyrin 1 (TRPA1) channel is a calcium permeable, non-selective cation channel, expressed in the sensory neurons and non-neuronal cells of different tissues. Initially studied for its role in pain and inflammation, TRPA1 has now functionally involved in multiple other physiological functions. TRPA1 channel has been extensively studied for modulation by pungent compounds present in the spices and herbs. In the last decade, the role of TRPA1 agonism in body weight reduction, secretion of hunger and satiety hormones, insulin secretion and thermogenesis, has unveiled the potential of the TRPA1 channel to be used as a preventive target to tackle obesity and associated comorbidities including insulin resistance in type 2 diabetes. In this review, we summarized the recent findings of TRPA1 based dietary/non-dietary modulation for its role in obesity prevention and therapeutics.
Regional Disparities in Obesity Among a Heterogeneous Population of Chinese Children and Adolescents.
Zhang Li,Chen JingNan,Zhang JianWei,Wu Wei,Huang Ke,Chen RuiMin,Maimaiti Mireguli,Chen ShaoKe,Cao BingYan,Zhu Min,Wang ChunLin,Su Zhe,Liang Yan,Yao Hui,Wei HaiYan,Zheng RongXiu,Du HongWei,Luo FeiHong,Li Pin,Mo MinJia,Yu YunXian,Wang Ergang,Dorazio Robert M,Fu Junfen
JAMA network open
Importance:Obesity is a public health challenge in China, but the geographical profiles of overweight and obesity among Chinese children are limited. Objective:To examine regional disparities in the prevalence of obesity among the heterogeneous population of Chinese children and adolescents to provide a more accurate profile of obesity among children in China. Design, Setting, and Participants:The Prevalence and Risk Factors for Obesity and Diabetes in Youth (PRODY) study was a cross-sectional survey study conducted from January 1, 2017, to December 31, 2019, among 201 098 children aged 3 to 18 years from 11 provinces, autonomous regions, and municipalities that produced a sample of Chinese children with a full range of ages and wide geographical coverage using a multistage, stratified, cluster-sampling design. Exposures:Five regions geographically representative of China (northern, eastern, southern, western, and central). Main Outcomes and Measures:The body weights and heights of all participants were measured. Multilevel, multinomial logistic regression models were used to estimate the prevalence of overweight and obesity. Results:Among 201 098 healthy children (105 875 boys [52.6%]; mean [SD] age, 9.8 [3.8] years) from eastern, southern, northern, central, and western China, the highest obesity prevalence was estimated for children aged 8 to 13 years in northern China (from 18.8% [95% CI, 16.2%-21.7%] to 23.6% [95% CI, 20.5%-26.9%]) and for boys aged 3 to 6 years in western China (from 18.1% [95% CI, 10.4%-29.4%] to 28.6% [95% CI, 14.3%-49.0%]). Boys had a higher prevalence than girls of obesity only in eastern and northern China, with a mean difference in prevalence of 4.6% (95% CI, 3.8%-5.4%) and 7.6% (95% CI, 6.5%-8.6%), respectively. Conclusions and Relevance:In this survey study, substantial geographic disparities in the prevalence of obesity and overweight were found among the heterogeneous population of Chinese children. The results suggest that special attention should be paid to vulnerable children and that regionally adapted interventions are needed to efficiently mitigate obesity in children.
The impact of obesity on adipocyte-derived extracellular vesicles.
Cellular and molecular life sciences : CMLS
Recently, the emerging roles of adipocyte-derived extracellular vesicles (EVs) linking obesity and its comorbidities have been recognized. In obese subjects, adipocytes are having hypertrophic growth and are under stressed. The dysfunction adipocytes dysregulate the assembly of the biological components in the EVs including exosomes. This article critically reviews the current findings on the impact of obesity on the exosomal cargo contents that induce the pathophysiological changes. Besides, this review also summarizes the understanding on how obesity affects the biogenesis of adipocyte-derived exosomes and the exosome secretion. Furthermore, the differences of the exosomal contents in different adipose depots, and the impact of obesity on the exosomes that are derived from the stromal vascular fraction such as the adipose tissue macrophages and adipocyte-derived stem cells will also be discussed. The current development and potential application of exosome-based therapy will be summarized. This review provides crucial information for the design of novel exosome-based therapy for the treatment of obesity and its comorbidities.
Morbid obesity but not obesity is associated with increased mortality in patients undergoing endoscopic retrograde cholangiopancreatography: A national cohort study.
Chen Bing,Yo Chia-Hung,Patel Ramya,Liu Bolun,Su Ke-Ying,Hsu Wan-Ting,Lee Chien-Chang
United European gastroenterology journal
BACKGROUND:The relationship between body weight and outcomes of endoscopic retrograde cholangiopancreatography (ERCP) is unclear. OBJECTIVES:This study aimed to investigate the impact of obesity and morbid obesity on mortality and ERCP-related complications in patients who underwent ERCP. METHODS:We conducted a US population-based retrospective cohort study using the Nationwide Readmissions Databases (2013-2014). A total of 159,264 eligible patients who underwent ERCP were identified, of which 137,158 (86.12%) were normal weight, 12,522 (7.86%) were obese, and 9584 (6.02%) were morbidly obese. The primary outcome was in-hospital mortality. The secondary outcomes were the length of stay, total cost, and ERCP-related complications. Multivariate analysis and propensity score (PS) matching analysis were performed. The analysis was repeated in a restricted cohort to eliminate confounders. RESULTS:Patients with morbid obesity, as compared to normal-weight patients, were associated with a significantly higher in-hospital mortality (hazard ratio [HR]: 5.54; 95% confidence interval [CI]: 1.23-25.04). Obese patients were not associated with significantly different mortality comparing to normal weight (HR: 1.00; 95% CI: 0.14-7.12). Patients with morbid obesity were also found to have an increased length of hospital stay and total cost. The rate of ERCP-related complications was comparable among the three groups except for a higher cholecystitis rate after ERCP in obese patients. CONCLUSIONS:Morbid obesity but not obesity was associated with increased mortality, length of stay, and total cost in patients undergoing ERCP.
The Obesity Society is turning 40: A history of the early years.
Bray George A,Greenwood M R C,Hansen Barbara C
Obesity (Silver Spring, Md.)
The North American Association for the Study of Obesity (NAASO), the precursor of The Obesity Society (TOS), was founded in 1981 and turns 40 years old in 2021. The Society was organized by George Bray along with John Brunzell, C. Wayne Callaway, M.R.C. Greenwood, and Judith Stern. It held its foundational meeting with a theme of "Types of Obesity: Animal Models and Clinical Applications" at Vassar College in the fall of 1982 along with symposia and an NIH workshop titled "Methods of Characterizing Human Obesity." At a follow-up meeting during the Fourth International Congress on Obesity, Barbara Hansen was elected President, Judith Stern Secretary, and Anne Sullivan Treasurer. Incorporation of NAASO occurred in 1984.
Perspectives and challenges of epigenetic determinants of childhood obesity: A systematic review.
Obesity reviews : an official journal of the International Association for the Study of Obesity
The tremendous increase in childhood obesity prevalence over the last few decades cannot merely be explained by genetics and evolutionary changes in the genome, implying that gene-environment interactions, such as epigenetic modifications, likely play a major role. This systematic review aims to summarize the evidence of the association between epigenetics and childhood obesity. A literature search was performed via PubMed and Scopus engines using a combination of terms related to epigenetics and pediatric obesity. Articles studying the association between epigenetic mechanisms (including DNA methylation and hydroxymethylation, non-coding RNAs, and chromatin and histones modification) and obesity and/or overweight (or any related anthropometric parameters) in children (0-18 years) were included. The risk of bias was assessed with a modified Newcastle-Ottawa scale for non-randomized studies. One hundred twenty-one studies explored epigenetic changes related to childhood obesity. DNA methylation was the most widely investigated mechanism (N = 101 studies), followed by non-coding RNAs (N = 19 studies) with evidence suggestive of an association with childhood obesity for DNA methylation of specific genes and microRNAs (miRNAs). One study, focusing on histones modification, was identified. Heterogeneity of findings may have hindered more insights into the epigenetic changes related to childhood obesity. Gaps and challenges that future research should face are herein described.
Memory and eating: A bidirectional relationship implicated in obesity.
Neuroscience and biobehavioral reviews
This paper reviews evidence demonstrating a bidirectional relationship between memory and eating in humans and rodents. In humans, amnesia is associated with impaired processing of hunger and satiety cues, disrupted memory of recent meals, and overconsumption. In healthy participants, meal-related memory limits subsequent ingestive behavior and obesity is associated with impaired memory and disturbances in the hippocampus. Evidence from rodents suggests that dorsal hippocampal neural activity contributes to the ability of meal-related memory to control future intake, that endocrine and neuropeptide systems act in the ventral hippocampus to provide cues regarding energy status and regulate learned aspects of eating, and that consumption of hypercaloric diets and obesity disrupt these processes. Collectively, this evidence indicates that diet-induced obesity may be caused and/or maintained, at least in part, by a vicious cycle wherein excess intake disrupts hippocampal functioning, which further increases intake. This perspective may advance our understanding of how the brain controls eating, the neural mechanisms that contribute to eating-related disorders, and identify how to treat diet-induced obesity.
Insulin resistance persists despite a metabolically healthy obesity phenotype.
Obesity (Silver Spring, Md.)
OBJECTIVE:Metabolically healthy obesity (MHO) is often defined as the absence of metabolic syndrome in the presence of obesity. However, phenotypic features of MHO are unclear. Insulin sensitivity in MHO was cross-sectionally compared with metabolically unhealthy obesity (MUO) and a reference group of young healthy participants without obesity. METHODS:Sedentary adults (n = 96) undergoing anthropometric, blood chemistries, maximal aerobic capacity, and euglycemic-hyperinsulinemic clamp measurements were classified by BMI (<25 and ≥30 kg/m ). MUO was defined as having obesity with metabolic syndrome (≥2 additional risk factors). Data were analyzed using a linear mixed models approach. RESULTS:Body weight was similar between MHO and MUO. Body fat (percentage) and high-density lipoprotein cholesterol were higher (p < 0.001), and systolic blood pressure, triglycerides, glucose, and insulin were lower in MHO versus MUO (p < 0.03, all). The MHO group also had lower high-density lipoprotein cholesterol and higher low-density lipoprotein cholesterol, diastolic blood pressure, and insulin compared with the reference. Both the MHO and MUO groups displayed impaired insulin sensitivity compared with the reference control (p < 0.001). CONCLUSIONS:Participants with MHO had distinct clinical measures related to hypertension, lipid metabolism, and glycemic control compared with a healthy reference group. Peripheral insulin resistance in obesity independent of metabolic status portends increased risk for type 2 diabetes in the MHO patient population.
Management of Obesity in Cardiovascular Practice: JACC Focus Seminar.
Journal of the American College of Cardiology
Obesity contributes to reduced life expectancy because of its link with type 2 diabetes and cardiovascular disease. Yet, targeting this poorly diagnosed, ill-defined, and underaddressed modifiable risk factor remains a challenge. In this review, we emphasize that the tendency among health care professionals to amalgam all forms of obesity altogether as a single entity may contribute to such difficulties and discrepancies. Obesity is a heterogeneous condition both in terms of causes and health consequences. Attention should be given to 2 prevalent subgroups of individuals: 1) patients who are overweight or moderately obese with excess visceral adipose tissue; and 2) patients with severe obesity, the latter group having distinct additional health issues related to their large body fat mass. The challenge of tackling high-cardiovascular-risk forms of obesity through a combination of personalized clinical approaches and population-based solutions is compounded by the current obesogenic environment and economy.
Anti-obesity drug discovery: advances and challenges.
Nature reviews. Drug discovery
Enormous progress has been made in the last half-century in the management of diseases closely integrated with excess body weight, such as hypertension, adult-onset diabetes and elevated cholesterol. However, the treatment of obesity itself has proven largely resistant to therapy, with anti-obesity medications (AOMs) often delivering insufficient efficacy and dubious safety. Here, we provide an overview of the history of AOM development, focusing on lessons learned and ongoing obstacles. Recent advances, including increased understanding of the molecular gut-brain communication, are inspiring the pursuit of next-generation AOMs that appear capable of safely achieving sizeable and sustained body weight loss.
More frequent olive oil intake is associated with reduced platelet activation in obesity.
Nutrition, metabolism, and cardiovascular diseases : NMCD
BACKGROUND AND AIMS:Obesity is an independent risk factor for atherosclerotic cardiovascular disease (CVD), and platelet hyperactivation in obesity may contribute to this association. Olive oil consumption is associated with lower cardiovascular disease (CVD) risk in the general population. However, little is known for individuals with obesity. We investigated whether olive oil intake is associated with platelet activation in obesity. METHODS AND RESULTS:We assessed platelet activation (surface P-selectin expression) with and without thrombin exposure and diet composition in 63 patients with severe obesity. Among 63 subjects with obesity, the mean age was 32.2 ± 8.0 years and BMI 44.1 ± 8.5 kg/m. Olive oil intake was stratified into <1 time/week (n = 21), 1-3 times/week (n = 18), ≥4 times/week (n = 24). Strata did not differ by age, BMI or platelet count. Unstimulated P-selectin expression did not differ by olive oil consumption. Subjects with more frequent olive oil intake exhibited lower P-selectin expression on submaximal thrombin exposure. CONCLUSIONS:More frequent olive oil intake is associated with reduced thrombin-induced platelet activation in obesity.
Childhood exposure to parental smoking and life-course overweight and central obesity.
Jaakkola Johanna M,Rovio Suvi P,Pahkala Katja,Viikari Jorma,Rönnemaa Tapani,Jula Antti,Niinikoski Harri,Mykkänen Juha,Juonala Markus,Hutri-Kähönen Nina,Kähönen Mika,Lehtimäki Terho,Raitakari Olli T
Annals of medicine
OBJECTIVE:To evaluate the association between childhood parental smoking exposure and the risk of overweight/obesity from childhood to adulthood. METHODS:This study leverages the data from two longitudinal population based cohort studies, the Cardiovascular Risk in Young Finns Study between years 1980-2011/2012 (YFS; = 2,303; baseline age 3-18 years) and the Special Turku Coronary Risk Factor Intervention Project between years 1989-2009/2010 (STRIP; = 632; baseline age 7 months). Weight, height and waist circumference were measured from childhood to adulthood. Overweight/obesity was defined as body mass index ≥25 kg/m in adults and using the Cole criteria in children. Central obesity was defined as waist circumference > 100/90 cm in men/women and as a waist-to-height ratio > 0.50 in children. Statistical analyses were adjusted for age, sex, socioeconomic status, smoking, birth weight, parental ages, diet and physical activity. RESULTS:Childhood parental smoking exposure was associated with increased risk for life-course overweight/obesity (YFS: RR1.13, 95%CI 1.02-1.24; STRIP: RR1.57, 95%CI 1.10-2.26) and central obesity (YFS: RR1.18, 95%CI 1.01-1.38; STRIP: RR1.45, 95%CI 0.98-2.15). CONCLUSIONS:Childhood exposure to parental smoking is associated with increased risk of overweight/obesity over the life-course. KEY MESSAGES Exposure to parental smoking in childhood was associated with increased risk of overweight/obesity, central obesity and adiposity measured by skinfold thickness from childhood to adulthood.
Janus kinase 2 (JAK2) methylation and obesity: A Mendelian randomization study.
Tu Runqi,Liu Xiaotian,Dong Xiaokang,Li Ruiying,Liao Wei,Hou Jian,Mao Zhenxing,Huo Wenqian,Wang Chongjian,Li Yuqian
Nutrition, metabolism, and cardiovascular diseases : NMCD
BACKGROUND AND AIMS:Janus kinase 2 (JAK2) play an important role in the energy metabolism. Whether there is a causal relationship between JAK2 methylation levels and obesity remains unclear. Based on the instrumental variables of 5 SNP sites, this study was aimed to explore the causal relationship between JAK2 methylation levels and obesity by Mendelian randomization analysis. METHODS AND RESULTS:A total of 1021 participants (511 cases and 510 controls defined by body mass index (BMI) ≥ 28.0 kg/m) was conducted from the Henan Rural Cohort study. SNPscan® was performed to test the SNP genotyping and MethylTarget™ was applied to detect the DNA methylation level. The logistic regression model was used to evaluate the associations between SNP or methylation of JAK2 and obesity (according to BMI). Mendelian randomization analysis was used to assess the potential causal association between JAK2 methylation and obesity. According to the logistic regression model, 1 CpG sit in the promotor was related to an increased risk of obesity (P < 0.05). 10 CpG sites in the exon were associated with decreased risk of obesity (P < 0.05). Mendelian randomization analysis showed a causal association between the methylated level of JAK2 and obesity, based on the instrumental variables of 5 SNPs (P < 0.05). CONCLUSIONS:This study supported that the methylation degree of JAK2 has a complex relationship with obesity, which might be related to the region of methylation. A causal relationship exists between the methylated level of JAK2 and obesity.
Obesity-associated cardiovascular risk in women: hypertension and heart failure.
Clinical science (London, England : 1979)
The pathogenesis of obesity-associated cardiovascular diseases begins long prior to the presentation of a cardiovascular event. In both men and women, cardiovascular events, and their associated hospitalizations and mortality, are often clinically predisposed by the presentation of a chronic cardiovascular risk factor. Obesity increases the risk of cardiovascular diseases in both sexes, however, the clinical prevalence of obesity, as well as its contribution to crucial cardiovascular risk factors is dependent on sex. The mechanisms via which obesity leads to cardiovascular risk is also discrepant in women between their premenopausal, pregnancy and postmenopausal phases of life. Emerging data indicate that at all reproductive statuses and ages, the presentation of a cardiovascular event in obese women is strongly associated with hypertension and its subsequent chronic risk factor, heart failure with preserved ejection fraction (HFpEF). In addition, emerging evidence indicates that obesity increases the risk of both hypertension and heart failure in pregnancy. This review will summarize clinical and experimental data on the female-specific prevalence and mechanisms of hypertension and heart failure in women across reproductive stages and highlight the particular risks in pregnancy as well as emerging data in a high-risk ethnicity in women of African ancestry (AA).
Adipocyte-Endothelium Crosstalk in Obesity.
Sabaratnam Rugivan,Svenningsen Per
Frontiers in endocrinology
Obesity is characterized by pathological adipose tissue (AT) expansion. While healthy AT expansion enhances systemic insulin sensitivity, unhealthy AT expansion through increased adipocyte size is associated with insulin resistance, fibrosis, hypoxia, and reduced adipose-derived adiponectin secretion. The mechanisms causing the unhealthy AT expansion are not fully elucidated; yet, dysregulated crosstalk between cells within the AT is an important contributor. Evidence from animal and human studies suggests a crucial role of the crosstalk between vascular endothelium (the innermost cell type in blood vessels) and adipocytes for metabolic homeostasis. Arterial endothelial cells are directly involved in maintaining normal organ functions through local blood flow regulation. The endothelial-dependent regulation of blood flow in AT is hampered in obesity, which negatively affects the adipocyte. Moreover, endothelial cells secrete extracellular vesicles (EVs) that target adipocytes . The endothelial EVs secretion is hampered in obesity and may be affected by the adipocyte-derived adipokine adiponectin. Adiponectin targets the vascular endothelium, eliciting organ-protective functions through binding to T-cadherin. The reduced obesity-induced adiponectin binding of T-cadherin reduces endothelial EV secretion. This affects endothelial health and cell-cell communication between AT cells and distant organs, influencing systemic energy homeostasis. This review focuses on the current understanding of endothelial and adipocyte crosstalk. We will discuss how obesity changes the AT environment and how these changes contribute to obesity-associated metabolic disease in humans. Particularly, we will describe and discuss the EV-dependent communication and regulation between adipocytes, adiponectin, and the endothelial cells regulating systemic energy homeostasis in health and metabolic disease in humans.
Genes in human obesity loci are causal obesity genes in C. elegans.
Ke Wenfan,Reed Jordan N,Yang Chenyu,Higgason Noel,Rayyan Leila,Wählby Carolina,Carpenter Anne E,Civelek Mete,O'Rourke Eyleen J
Obesity and its associated metabolic syndrome are a leading cause of morbidity and mortality. Given the disease's heavy burden on patients and the healthcare system, there has been increased interest in identifying pharmacological targets for the treatment and prevention of obesity. Towards this end, genome-wide association studies (GWAS) have identified hundreds of human genetic variants associated with obesity. The next challenge is to experimentally define which of these variants are causally linked to obesity, and could therefore become targets for the treatment or prevention of obesity. Here we employ high-throughput in vivo RNAi screening to test for causality 293 C. elegans orthologs of human obesity-candidate genes reported in GWAS. We RNAi screened these 293 genes in C. elegans subject to two different feeding regimens: (1) regular diet, and (2) high-fructose diet, which we developed and present here as an invertebrate model of diet-induced obesity (DIO). We report 14 genes that promote obesity and 3 genes that prevent DIO when silenced in C. elegans. Further, we show that knock-down of the 3 DIO genes not only prevents excessive fat accumulation in primary and ectopic fat depots but also improves the health and extends the lifespan of C. elegans overconsuming fructose. Importantly, the direction of the association between expression variants in these loci and obesity in mice and humans matches the phenotypic outcome of the loss-of-function of the C. elegans ortholog genes, supporting the notion that some of these genes would be causally linked to obesity across phylogeny. Therefore, in addition to defining causality for several genes so far merely correlated with obesity, this study demonstrates the value of model systems compatible with in vivo high-throughput genetic screening to causally link GWAS gene candidates to human diseases.
Obesity alters the ovarian proteomic response to zearalenone exposure†.
González-Alvarez M Estefanía,McGuire Bailey C,Keating Aileen F
Biology of reproduction
Zearalenone (ZEN), a nonsteroidal estrogenic mycotoxin, is detrimental to female reproduction. Altered chemical biotransformation, depleted primordial follicles and a blunted genotoxicant response have been discovered in obese female ovaries, thus, this study investigated the hypothesis that obesity would enhance ovarian sensitivity to ZEN exposure. Seven-week-old female wild-type nonagouti KK.Cg-a/a mice (lean) and agouti lethal yellow KK.Cg-Ay/J mice (obese) received food and water ad libitum, and either saline or ZEN (40 μg/kg) per os for 15 days. Body and organ weights, and estrous cyclicity were recorded, and ovaries collected posteuthanasia for protein analysis. Body and liver weights were increased (P < 0.05) in the obese mice, but obesity did not affect (P > 0.05) heart, kidney, spleen, uterus, or ovary weight and there was no impact (P > 0.05) of ZEN exposure on body or organ weight in lean or obese mice. Obese mice had shorter proestrus (P < 0.05) and a tendency (P = 0.055) for longer metestrus/diestrus. ZEN exposure in obese mice increased estrus but shortened metestrus/diestrus length. Neither obesity nor ZEN exposure impacted (P > 0.05) circulating progesterone, or ovarian abundance of EPHX1, GSTP1, CYP2E1, ATM, BRCA1, DNMT1, HDAC1, H4K16ac, or H3K9me3. Lean mice exposed to ZEN had a minor increase in γH2AX abundance (P < 0.05). In lean and obese mice, LC-MS/MS identified alterations to proteins involved in chemical metabolism, DNA repair and reproduction. These data identify ZEN-induced adverse ovarian modes of action and suggest that obesity is additive to ZEN-induced ovotoxicity.
Associations between socioeconomic status and obesity, sarcopenia, and sarcopenic obesity in community-dwelling older adults: The Tasmanian Older Adult Cohort Study.
Gandham Anoohya,Zengin Ayse,Bonham Maxine P,Brennan-Olsen Sharon L,Aitken Dawn,Winzenberg Tania M,Ebeling Peter R,Jones Graeme,Scott David
BACKGROUND:Social disadvantage may contribute to increased prevalence of sarcopenia and obesity. This study investigated if socioeconomic factors are associated with obesity, sarcopenia, or sarcopenic obesity (SO), in community-dwelling older adults. METHODS:This was a cross-sectional analysis of data from the Tasmanian Older Adult Cohort study. Obesity was defined by body fat percentage (Men: ≥25%; Women: ≥35%) and sarcopenia was defined as the lowest 20% of sex-specific appendicular lean mass (ALM)/height (m) and handgrip strength. Socioeconomic factors investigated were education (tertiary degree, secondary or no secondary school), occupation (high skilled white-collar, low skilled white-collar, or blue-collar) and residential area (advantaged or disadvantaged area). Multinomial logistic regression analyses yielding odds ratios (95% confidence intervals) were performed and adjusted for potential confounders. Mediation analysis was performed. RESULTS:1099 older adults (63.0 ± 7.5 years; 51.1% women) participated. Older adults with a tertiary degree were significantly less likely to have obesity (0.68; 0.47, 0.98) and SO (0.48; 0.24, 0.94) compared with those who had no secondary schooling. No associations were found for occupation. Similarly, older adults living in advantaged areas were significantly less likely to have obesity (0.61; 0.39, 0.95). Steps per day mediated the association between residential area and body fat percentage by 51%. CONCLUSION:Lower educational attainment, but not occupation, was associated with increased likelihood for both obesity and SO in community-dwelling older adults. Low physical activity levels in disadvantaged areas substantially contributed to higher obesity prevalence in this population. Further research is necessary to confirm whether similar associations exist in populations with greater levels of social disadvantage and to design effective community-based interventions.
Childhood overweight and obesity in Europe: Changes from 2007 to 2017.
Buoncristiano Marta,Spinelli Angela,Williams Julianne,Nardone Paola,Rito Ana Isabel,García-Solano Marta,Grøholt Else Karin,Gutiérrez-González Enrique,Klepp Knut Inge,Starc Gregor,Petrauskienė Aušra,Kunešová Marie,Hassapidou Maria,Pérez-Farinós Napoleón,Pudule Iveta,Kelleher Cecily C,Duleva Vesselka,Rakovac Ivo,Chatterjee Saion,Breda João
Obesity reviews : an official journal of the International Association for the Study of Obesity
The Childhood Obesity Surveillance Initiative (COSI) routinely measures height and weight of primary school children aged 6-9 years and calculates overweight and obesity prevalence within the World Health Organization (WHO) European Region using a standard methodology. This study examines the trends in the prevalence of overweight and obesity from the first round of COSI carried out in 2007/2008 to the latest of 2015/2017 in 11 European countries in which data were collected for at least three rounds. In total 303,155 children were measured. In general, the prevalence of overweight and obesity among boys and girls decreased in countries with high prevalence (Southern Europe) and remained stable or slightly increased in Northern European and Eastern European countries included in the analysis. Among boys, the highest decrease in overweight (including obesity) was observed in Portugal (from 40.5% in 2007/2008 to 28.4 in 2015/2017) and in Greece for obesity (from 30.5% in 2009/2010 to 21.7% in 2015/2017). Lithuania recorded the strongest increase in the proportion of boys with overweight (from 24.8% to 28.5%) and obesity (from 9.4% to 12.2%). The trends were similar for boys and girls in most countries. Several countries in Europe have successfully implemented policies and interventions to counteract the increase of overweight and obesity, but there is still much to be done.
Surgery for Obesity and Weight-Related Diseases Changes the Inflammatory Profile in Women with Severe Obesity: a Randomized Controlled Clinical Trial.
de Sousa Alan Robson Trigueiro,Freitas Junior Wilson Rodrigues,Perez Eduardo Araujo,Ilias Elias Jirjoss,Silva Anderson Soares,Alves Vera Lucia Santos,Afonso João Pedro Ribeiro,Oliveira Miriã Cândida,Fonseca Adriano Luís,da Silva Marcos Mota,Lino Maria Eduarda Moreira,Oliveira Junior Manoel Carneiro,Vieira Rodolfo Paula,Pedro Wilson José Sena,Bachi André Luis Lacerda,Insalaco Giuseppe,Malheiros Carlos Alberto,Oliveira Luis Vicente Franco
INTRODUCTION/PURPOSE:Obesity increases significantly every year worldwide. Since 1980, the prevalence of individuals with obesity has practically doubled. Obesity plays an important role in the pathophysiology of diseases that arise from a complex interaction of nutritional, genetic, and metabolic factors, characterizing a chronic inflammatory state. This study aimed to verify the systemic inflammatory response through the analysis of IGF-1, IL-23, and resistin levels and the lipid profile in severely obese women undergoing surgery for obesity and weight-related diseases. MATERIALS AND METHODS:This randomized controlled clinical trial includes female patients clinically diagnosed with severe obesity with an indication for bariatric surgery. RESULTS:In the initial evaluation, no significant difference was observed between the control (CG) and bariatric surgery (BSG) groups. The weight, BMI, systolic and diastolic blood pressures, total cholesterol, LDL, HDL, total non-HDL cholesterol, and glucose in BSG patients showed a significant change after surgery. Pre- and post-surgery levels of resistin, IGF-1, and IL-23 showed a significant difference in the BSG group, but only IL-23 was changed after 6 months in the CG. CONCLUSION:The results of this study confirmed that weight loss induced by surgery for obesity and weight-related diseases improved the lipid profile and reduced the chronic inflammatory status in women with severe obesity.
Web Support for Weight-Loss Interventions: PREDIRCAM2 Clinical Trial Baseline Characteristics and Preliminary Results.
Alcántara-Aragón Valeria,Rodrigo-Cano Susana,Lupianez-Barbero Ascension,Martinez María José,Martinez Carmen,Tapia José,Iniesta José Manuel,Tenes Susana,Urgell Eulalia,Navarro Gemma,Hernando M Elena,Merino-Torres Juan Francisco,de Leiva Alberto,Gonzalez Cintia
Diabetes technology & therapeutics
An ongoing clinical trial is testing the efficacy of web telematic support in a structured program for obesity treatment and diabetes prevention. Participants were recruited from two tertiary-care hospitals and randomized to receive either a telematic intervention (TI) supported by PREDIRCAM2 web platform or a non-telematic intervention (NTI). All receive 1-year follow-up. Both interventions consist of tailored dietary and exercise prescriptions, based on a Mediterranean dietary pattern and general WHO exercise recommendations for adults. At 6 months, both groups have received 7 contacts, 3 exclusively telematic for the TI group. This is a preliminary result intention-to-treat analysis. One hundred eighty-three participants were recruited, with a mean body mass index of 34.75 ± 2.75 kg/m. General dropout rate at 6 months was 26.8%. Weight changes were statistically significant at months 3 and 6 compared to baseline, -2.915 ± 0.24 kg, -3.29 ± 0.36 kg, respectively (P < 0.001), but not statistically significant between the 3- and 6-month time points -0.37 ± 0.21 kg (P = 0.24). Mean group differences showed that the TI group lost 1.61 ± 1.88 kg more than the NTI group (P = 0.39). Waist, waist/hip ratio, resting heart rate, blood pressure, HbA1c, and low-density lipoprotein cholesterol also showed statistically significant changes at 6 months, with no significant differences between groups. Weight loss in the TI group shows similar results as the usual care NTI group for weight loss and control of obesity comorbidities. At completion of the clinical trial, these results will be reevaluated to assess the potential role of web support in weight-loss maintenance and its cost-effectiveness.
The effect of ultra-processed very low-energy diets on gut microbiota and metabolic outcomes in individuals with obesity: A systematic literature review.
Lane Melissa,Howland Gina,West Madeline,Hockey Meghan,Marx Wolfgang,Loughman Amy,O'Hely Martin,Jacka Felice,Rocks Tetyana
Obesity research & clinical practice
This systematic review investigated the effects of ultra-processed very low-energy diets on gut microbiota and metabolic outcomes in individuals with obesity. MEDLINE complete, EMBASE, Scopus, Cochrane and CINAHL were searched between date of inception and October 2019. Seven trials were reviewed (a total of 130 participants, with 10 to 44 participants in each trial). Of these, five were single-arm interventions and included very low-energy diets adjunctive to comprehensive lifestyle interventions such as nutritional counselling, behavioural therapy and exercise programmes. Changes to taxa within the Firmicutes phylum were found, including reduced abundance of potentially beneficial butyrogenic microbes (Roseburia, Faecalbacterium prausnitzii, Lactobacillus, Bifidobacterium and Lachnospiraeceae). Conversely, increased abundance of potentially pathogenic or opportunistic microbes from the Bacteroidetes phylum was reported, including increases in Alistipes and Bacteroides taxa. However, outcomes were inconsistent, with some trials also showing decreases in Bacteroides taxa and increases in commensal microbiota, such as Lachnospiraceae and Bifidobacteriaceae. The changes in metabolic parameters observed from baseline to after the ultra-processed very low-energy diets were mostly beneficial or were not significantly altered. Although the selected articles were deemed to have satisfactory methodological quality, to understand the possible direct effects of these regimens on gut microbiota, further rigorously designed trials, with more standardised microbiological sequencing techniques and detailed reporting, are required. Study registration: Prospero ID: CRD42019124436.
Effects of IL-33 on 3T3-L1 cells and obese mice models induced by a high-fat diet.
Kai Yue,Gao Jingtao,Liu Hu,Wang Yubing,Tian Chenrui,Guo Sheng,He Ling,Li Min,Tian Zhongwei,Song Xiangfeng
Obesity is a syndrome that attributes to many factors such as genetics, diet, lifestyle and environment, which includes an imbalance of immune regulation. IL-33, as a new member of the IL-1 family, is classically associated with type 2 immune responses. Here, IL-33 was investigated for its ability to optimize lipid aggregation and ameliorate the inflammatory response in obesity. In vitro experimental results showed that, compared with the induction group, the treatment with 30 ng/mL IL-33 displayed a reduction in the number of lipid droplets. The expression levels of AceCS1 and PPARγ also decreased in the 30 ng/mL IL-33 group compared to the induction group. For confirmation in vivo, three groups of C57BL/6 mice were treated for 14 weeks: mice in control were fed with a normal diet; mice in the HFD and IL-33 groups were fed with a high-fat diet (HFD) and with sterile PBS or recombinant IL-33, respectively. Liver, muscle, spleen and four types of adipose tissue, as well as serum, were collected for further testing. Our data demonstrated that after 4-week treatment with recombinant IL-33, metabolic parameters in mice were improved significantly (visceral fat weight, glucose and insulin tolerance, liver steatosis, expression of lipid synthesis index and inflammatory response). Moreover, IL-33 treatment regulated the original distribution of IL-33 among different tissues. Hence, IL-33 modulated lipid metabolism and inflammatory response in obesity, which would be a novel therapeutic target for obesity and related metabolic diseases.
How the placenta-brain lipid axis impacts the nutritional origin of child neurodevelopmental disorders: Focus on attention deficit hyperactivity disorder and autism spectrum disorder.
Tarui Tomo,Rasool Aisha,O'Tierney-Ginn Perrie
Dietary fish is a rich source of omega-3 (n-3) fatty acids, and as such, is believed to have played an important role in the evolution of the human brain and its advanced cognitive function. The long chain polyunsaturated fatty acids, particularly the n-3 docosahexanoic acid (DHA), are critical for proper neurological development and function. Both low plasma DHA and obesity in pregnancy are associated with neurodevelopmental disorders such as attention deficit and hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) in childhood, and n-3 supplementation has been shown to improve symptoms, as reviewed herein. The mechanisms underlying the connection between maternal obesity, n-3 fatty acid levels and offspring's neurological outcomes are poorly understood, but we review the evidence for a mediating role of the placenta in this relationship. Despite promising data that n-3 fatty acid supplementation mitigates the effect of maternal obesity on placental lipid metabolism, few clinical trials or animal studies have considered the neurological outcomes of offspring of mothers with obesity supplemented with n-3 FA in pregnancy.
Short-term and long-term effects of major depressive disorder subtypes on obesity markers and impact of sex on these associations.
Ottino Clémentine,Strippoli Marie-Pierre F,Gholam Mehdi,Lasserre Aurélie M,Vandeleur Caroline L,Vollenweider Peter,Marques-Vidal Pedro,Clair Carole,Preisig Martin
Journal of affective disorders
BACKGROUND:Only a few studies with conflicting results have examined the effects of sex on the prospective association between depression and subsequent obesity. OBJECTIVE:(1) To simultaneously assess the associations of the subtypes (atypical, melancholic, unspecified) of major depressive disorder (MDD) measured at baseline and subtypes of major depressive episodes (MDE) that emerged during a 5.5-year follow-up with changes in obesity markers (body mass index, waist circumference, fat mass) during this follow-up, and (2) to test the effect of sex on these associations. METHODS:Data from CoLaus|PsyCoLaus, a population-based cohort study including 2702 participants (50.1% women, mean age 49.6 years). Criteria for mental disorders were elicited using semi-structured interviews. RESULTS:History of atypical MDD at baseline was associated with a steeper increase in BMI and waist circumference, whereas atypical MDE during follow-up was associated with a steeper increase in the three studied obesity markers. Melancholic MDD at baseline was associated with a steeper increase in BMI. Several significant interactions with sex were found indicating higher increase in fat mass in men than in women following melancholic MDD reported at baseline, higher decrease in BMI and fat mass in women than in men related to melancholic MDE emerging during follow-up and higher increase in waist circumference in men than in women following unspecified MDD reported at baseline. LIMITATIONS:Urban sample which may not be representative for the whole population. CONCLUSIONS:Our results further advocate for the specific need of a thorough monitoring of obesity markers in patients with atypical MDD and suggest less favorable obesity marker changes mainly related to melancholic MDE in men.
Combined association of central obesity and depressive symptoms with risk of heart disease: A prospective cohort study.
Wang Xiaowen,Hu Yonghua,Qin Li-Qiang,Dong Jia-Yi
Journal of affective disorders
OBJECTIVE:To examine the combined association of central obesity and depressive symptoms with risk of heart disease in a national prospective cohort study of the Chinese population. METHODS:Data came from 10,722 community-dwelling adults aged over 45 years, from the China Health and Retirement Longitudinal Study during 2011-2018. Central obesity was assessed with waist circumference (WC) in physical examinations (men with a WC of ≥ 90 cm and women with a WC of ≥ 80 cm). Depressive symptoms were assessed using the 10-item Center for Epidemiologic Studies Depression Scale (score ≥ 10). Participants were assigned to four groups according to central obesity (yes/no) and depressive symptoms (yes/no). Cox proportional hazard regression was used after adjusting for covariates. RESULTS:During 7 years of follow-up, we identified 1080 heart disease cases. Compared with people without central obesity and depressive symptoms, the multivariable-adjusted hazard ratios (95% confidence intervals) were 1.39 (1.18, 1.64) for those who had central obesity alone, 1.44 (1.18, 1.77) for those who had depressive symptoms alone, and 1.88 (1.55, 2.30) for those who had both central obesity and depressive symptoms. The combined association in men was more evident than that in women. CONCLUSIONS:Our study provided evidence that the coexistence of central obesity and depressive symptoms were associated with a substantially increased risk of heart disease compared to those without these two conditions.
NLRP3 inflammasome is a key driver of obesity-induced atrial arrhythmias.
Scott Larry,Fender Anke C,Saljic Arnela,Li Luge,Chen Xiaohui,Wang Xiaolei,Linz Dominik,Lang Jilu,Hohl Mathias,Twomey Darragh,Pham Thuy T,Diaz-Lankenau Rodrigo,Chelu Mihail G,Kamler Markus,Entman Mark L,Taffet George E,Sanders Prashanthan,Dobrev Dobromir,Li Na
AIMS:Obesity, an established risk factor of atrial fibrillation (AF), is frequently associated with enhanced inflammatory response. However, whether inflammatory signaling is causally linked to AF pathogenesis in obesity remains elusive. We recently demonstrated that the constitutive activation of the 'NACHT, LRR, and PYD Domains-containing Protein 3' (NLRP3) inflammasome promotes AF susceptibility. In this study, we hypothesized that the NLRP3 inflammasome is a key driver of obesity-induced AF. METHODS AND RESULTS:Western blotting was performed to determine the level of NLRP3 inflammasome activation in atrial tissues of obese patients, sheep, and diet-induced obese (DIO) mice. The increased body weight in patients, sheep, and mice was associated with enhanced NLRP3-inflammasome activation. To determine whether NLRP3 contributes to the obesity-induced atrial arrhythmogenesis, wild-type (WT) and NLRP3 homozygous knockout (NLRP3-/-) mice were subjected to high-fat-diet (HFD) or normal chow (NC) for 10 weeks. Relative to NC-fed WT mice, HFD-fed WT mice were more susceptible to pacing-induced AF with longer AF duration. In contrast, HFD-fed NLRP3-/- mice were resistant to pacing-induced AF. Optical mapping in DIO mice revealed an arrhythmogenic substrate characterized by abbreviated refractoriness and action potential duration (APD), two key determinants of reentry-promoting electrical remodeling. Upregulation of ultra-rapid delayed-rectifier K+-channel (Kv1.5) contributed to the shortening of atrial refractoriness. Increased profibrotic signaling and fibrosis along with abnormal Ca2+ release from sarcoplasmic reticulum (SR) accompanied atrial arrhythmogenesis in DIO mice. Conversely, genetic ablation of Nlrp3 (NLRP3-/-) in HFD-fed mice prevented the increases in Kv1.5 and the evolution of electrical remodeling, the upregulation of profibrotic genes, and abnormal SR Ca2+ release in DIO mice. CONCLUSION:These results demonstrate that the atrial NLRP3 inflammasome is a key driver of obesity-induced atrial arrhythmogenesis and establishes a mechanistic link between obesity-induced AF and NLRP3-inflammasome activation.
Leptin Augments Antitumor Immunity in Obesity by Repolarizing Tumor-Associated Macrophages.
Journal of immunology (Baltimore, Md. : 1950)
Although obesity can promote cancer, it may also increase immunotherapy efficacy in what has been termed the obesity-immunotherapy paradox. Mechanisms of this effect are unclear, although obesity alters key inflammatory cytokines and can promote an inflammatory state that may modify tumor-infiltrating lymphocytes and tumor-associated macrophage populations. To identify mechanisms by which obesity affects antitumor immunity, we examined changes in cell populations and the role of the proinflammatory adipokine leptin in immunotherapy. Single-cell RNAseq demonstrated that obesity decreased tumor-infiltrating lymphocyte frequencies, and flow cytometry confirmed altered macrophage phenotypes with lower expression of inducible NO synthase and MHC class II in tumors of obese animals. When treated with anti-programmed cell death protein 1 (PD-1) Abs, however, obese mice had a greater absolute decrease in tumor burden than lean mice and a repolarization of the macrophages to inflammatory M1-like phenotypes. Mechanistically, leptin is a proinflammatory adipokine that is induced in obesity and may mediate enhanced antitumor immunity in obesity. To directly test the effect of leptin on tumor growth and antitumor immunity, we treated lean mice with leptin and observed tumors over time. Treatment with leptin, acute or chronic, was sufficient to enhance antitumor efficacy similar to anti-PD-1 checkpoint therapy. Further, leptin and anti-PD-1 cotreatment may enhance antitumor effects consistent with an increase in M1-like tumor-associated macrophage frequency compared with non-leptin-treated mice. These data demonstrate that obesity has dual effects in cancer through promotion of tumor growth while simultaneously enhancing antitumor immunity through leptin-mediated macrophage reprogramming.
Obesity and insulin resistance: Pathophysiology and treatment.
Tong Yue,Xu Sai,Huang Lili,Chen Chen
Drug discovery today
The prevalence of obesity is a major cause of many chronic metabolic disorders, including type 2 diabetes mellitus (T2DM), cardiovascular disease (CVD), and cancer. Insulin resistance is often associated with metabolic unhealthy obesity (MUO). Therapeutic approaches aiming to improve insulin sensitivity are believed to be central for the prevention and treatment of MUO. However, current antiobesity drugs are reported as multitargeted and their insulin-sensitizing effects remain unclear. In this review, we discuss current understanding of the mechanisms of insulin resistance from the aspects of endocrine disturbance, inflammation, oxidative, and endoplasmic reticulum stress (ERS). We then summarize the antiobesity drugs, focusing on their effects on insulin sensitivity. Finally, we discuss strategies for obesity treatment.
Obesity, kidney dysfunction, and inflammation: interactions in hypertension.
Hall John E,Mouton Alan J,da Silva Alexandre A,Omoto Ana C M,Wang Zhen,Li Xuan,do Carmo Jussara M
Obesity contributes 65-75% of the risk for human primary (essential) hypertension (HT) which is a major driver of cardiovascular and kidney diseases. Kidney dysfunction, associated with increased renal sodium reabsorption and compensatory glomerular hyperfiltration, plays a key role in initiating obesity-HT and target organ injury. Mediators of kidney dysfunction and increased blood pressure include (i) elevated renal sympathetic nerve activity (RSNA); (ii) increased antinatriuretic hormones such as angiotensin II and aldosterone; (iii) relative deficiency of natriuretic hormones; (iv) renal compression by fat in and around the kidneys; and (v) activation of innate and adaptive immune cells that invade tissues throughout the body, producing inflammatory cytokines/chemokines that contribute to vascular and target organ injury, and exacerbate HT. These neurohormonal, renal, and inflammatory mechanisms of obesity-HT are interdependent. For example, excess adiposity increases the adipocyte-derived cytokine leptin which increases RSNA by stimulating the central nervous system proopiomelanocortin-melanocortin 4 receptor pathway. Excess visceral, perirenal and renal sinus fat compress the kidneys which, along with increased RSNA, contribute to renin-angiotensin-aldosterone system activation, although obesity may also activate mineralocorticoid receptors independent of aldosterone. Prolonged obesity, HT, metabolic abnormalities, and inflammation cause progressive renal injury, making HT more resistant to therapy and often requiring multiple antihypertensive drugs and concurrent treatment of dyslipidaemia, insulin resistance, diabetes, and inflammation. More effective anti-obesity drugs are needed to prevent the cascade of cardiorenal, metabolic, and immune disorders that threaten to overwhelm health care systems as obesity prevalence continues to increase.
Obesity and Cardiovascular Disease: The Emerging Role of Inflammation.
Khafagy Rana,Dash Satya
Frontiers in cardiovascular medicine
Obesity is a growing public health challenge across the globe. It is associated with increased morbidity and mortality. Cardiovascular disease (CVD) is the leading cause of mortality for people with obesity. Current strategies to reduce CVD are largely focused on addressing traditional risk factors such as dyslipidemia, type 2 diabetes (T2D) and hypertension. Although this approach is proven to reduce CVD, substantial residual risk remains for people with obesity. This necessitates a better understanding of the etiology of CVD in people with obesity and alternate therapeutic approaches. Reducing inflammation may be one such strategy. A wealth of animal and human data indicates that obesity is associated with adipose tissue and systemic inflammation. Inflammation is a known contributor to CVD in humans and can be successfully targeted to reduce CVD. Here we will review the etiology and pathogenesis of inflammation in obesity associated metabolic disease as well as CVD. We will review to what extent these associations are causal based on human genetic studies and pharmacological studies. The available data suggests that anti-inflammatory treatments can be used to reduce CVD, but off-target effects such as increased infection have precluded its broad therapeutic application to date. The role of anti-inflammatory therapies in improving glycaemia and metabolic parameters is less established. A number of clinical trials are currently ongoing which are evaluating anti-inflammatory agents to lower CVD. These studies will further clarify whether anti-inflammatory agents can safely reduce CVD.
Immunometabolic Dysregulation at the Intersection of Obesity and COVID-19.
Khwatenge Collins N,Pate Marquette,Miller Laura C,Sang Yongming
Frontiers in immunology
Obesity prevails worldwide to an increasing effect. For example, up to 42% of American adults are considered obese. Obese individuals are prone to a variety of complications of metabolic disorders including diabetes mellitus, hypertension, cardiovascular disease, and chronic kidney disease. Recent meta-analyses of clinical studies in patient cohorts in the ongoing coronavirus-disease 2019 (COVID-19) pandemic indicate that the presence of obesity and relevant disorders is linked to a more severe prognosis of COVID-19. Given the significance of obesity in COVID-19 progression, we provide a review of host metabolic and immune responses in the immunometabolic dysregulation exaggerated by obesity and the viral infection that develops into a severe course of COVID-19. Moreover, sequela studies of individuals 6 months after having COVID-19 show a higher risk of metabolic comorbidities including obesity, diabetes, and kidney disease. These collectively implicate an inter-systemic dimension to understanding the association between obesity and COVID-19 and suggest an interdisciplinary intervention for relief of obesity-COVID-19 complications beyond the phase of acute infection.
The links between sleep duration, obesity and type 2 diabetes mellitus.
The Journal of endocrinology
Global rates of obesity and type 2 diabetes mellitus (T2DM) are increasing globally concomitant with a rising prevalence of sleep deprivation and sleep disorders. Understanding the links between sleep, obesity and T2DM might offer an opportunity to develop better prevention and treatment strategies for these epidemics. Experimental studies have shown that sleep restriction is associated with changes in energy homeostasis, insulin resistance and β-cell function. Epidemiological cohort studies established short sleep duration as a risk factor for developing obesity and T2DM. In addition, small studies suggested that short sleep duration was associated with less weight loss following lifestyle interventions or bariatric surgery. In this article, we review the epidemiological evidence linking sleep duration to obesity and T2DM and plausible mechanisms. In addition, we review the impact of changes in sleep duration on obesity and T2DM.
Relationship between type 2 cytokine and inflammasome responses in obesity-associated asthma.
The Journal of allergy and clinical immunology
BACKGROUND:Obesity is a risk factor for asthma, and obese asthmatic individuals are more likely to have severe, steroid-insensitive disease. How obesity affects the pathogenesis and severity of asthma is poorly understood. Roles for increased inflammasome-mediated neutrophilic responses, type 2 immunity, and eosinophilic inflammation have been described. OBJECTIVE:We investigated how obesity affects the pathogenesis and severity of asthma and identified effective therapies for obesity-associated disease. METHODS:We assessed associations between body mass index and inflammasome responses with type 2 (T2) immune responses in the sputum of 25 subjects with asthma. Functional roles for NLR family, pyrin domain-containing (NLRP) 3 inflammasome and T2 cytokine responses in driving key features of disease were examined in experimental high-fat diet-induced obesity and asthma. RESULTS:Body mass index and inflammasome responses positively correlated with increased IL-5 and IL-13 expression as well as C-C chemokine receptor type 3 expression in the sputum of subjects with asthma. High-fat diet-induced obesity resulted in steroid-insensitive airway hyperresponsiveness in both the presence and absence of experimental asthma. High-fat diet-induced obesity was also associated with increased NLRP3 inflammasome responses and eosinophilic inflammation in airway tissue, but not lumen, in experimental asthma. Inhibition of NLRP3 inflammasome responses reduced steroid-insensitive airway hyperresponsiveness but had no effect on IL-5 or IL-13 responses in experimental asthma. Depletion of IL-5 and IL-13 reduced obesity-induced NLRP3 inflammasome responses and steroid-insensitive airway hyperresponsiveness in experimental asthma. CONCLUSION:We found a relationship between T2 cytokine and NLRP3 inflammasome responses in obesity-associated asthma, highlighting the potential utility of T2 cytokine-targeted biologics and inflammasome inhibitors.
Sarcopenia, Obesity, and Sarcopenic Obesity: Relationship with Skeletal Muscle Phenotypes and Single Nucleotide Polymorphisms.
Khanal Praval,Williams Alun G,He Lingxiao,Stebbings Georgina K,Onambele-Pearson Gladys L,Thomis Martine,Degens Hans,Morse Christopher I
Journal of clinical medicine
Obesity may aggravate the effects of sarcopenia on skeletal muscle structure and function in the elderly, but no study has attempted to identify the gene variants associated with sarcopenia in obese women. Therefore, the aims of the present study were to: (1) describe neuromuscular function in sarcopenic and non-sarcopenic women with or without obesity; (2) identify gene variants associated with sarcopenia in older obese women. In 307 Caucasian women (71 ± 6 years, 66.3 ± 11.3 kg), skeletal muscle mass was estimated using bioelectric impedance, and function was tested with a 30 s one-leg standing-balance test. Biceps brachii thickness and vastus lateralis cross-sectional area (VL) were measured with B-mode ultrasonography. Handgrip strength, maximum voluntary contraction elbow flexion (MVC), and knee extension torque (MVC) were measured by dynamometry, and MVC/VL was calculated. Genotyping was performed for 24 single-nucleotide polymorphisms (SNPs), selected based on their previous associations with muscle-related phenotypes. Based on sarcopenia and obesity thresholds, groups were classified as sarcopenic obese, non-sarcopenic obese, sarcopenic non-obese, or non-sarcopenic non-obese. A two-way analysis of covariance was used to assess the main effects of sarcopenia and obesity on muscle-related phenotypes and binary logistic regression was performed for each SNP to investigate associations with sarcopenia in obesity. There were no significant obesity * sarcopenic status interactions for any of the investigated muscle-related phenotypic parameters. Neither sarcopenia nor obesity had a significant effect on biceps brachii thickness, but sarcopenia was associated with lower VL ( = 0.003). Obesity was associated with lower MVC ( = 0.032), MVC ( = 0.047), and MVC/VL ( = 0.012) with no significant effect of sarcopenia. Adjusted for age and height, three SNPs ( rs1815739, rs1801131, and rs1537516) were associated with sarcopenia in obese participants. Sarcopenia was associated with a smaller muscle size, while obesity resulted in a lower muscle quality irrespective of sarcopenia. Three gene variants ( rs1815739, rs1801131, and rs1537516) suspected to affect muscle function, homocysteine metabolism, or DNA methylation, respectively, were associated with sarcopenia in obese elderly women. Understanding the skeletal muscle features affected by sarcopenia and obesity, and identification of genes related to sarcopenia in obese women, may facilitate early detection of individuals at particular risk of sarcopenic obesity.
Approach to Obesity in the Elderly.
Buch Assaf,Marcus Yonit,Shefer Gabi,Zimmet Paul,Stern Naftali
The Journal of clinical endocrinology and metabolism
Until recently, weight loss in the elderly obese was feared due to ensuing muscle loss and frailty. Facing overall increasing longevity, high rates of obesity in older subjects (≥65 years) and a growing recognition of the health and functional cost of the number of obesity years, abetted by evidence that intentional weight loss in older obese subjects is safe, this approach is gradually, but not unanimously, being replaced by more active principles. Lifestyle interventions that include reduced but sufficient energy intake, age-adequate protein and micronutrient intake, coupled with aerobic and resistance exercise tailored to personal limitations can induce weight loss with improvement in frailty indices. Sustained weight loss in this age can prevent/ameliorate diabetes. More active steps are controversial. The use of weight loss medications, particularly GLP-1 analogs (liraglutide as the first example), provides an additional treatment tier. Its safety and cardiovascular health benefits have been convincingly shown in elderly obese subjects with type 2 diabetes. In our opinion, this option should not be denied to obese subjects with prediabetes or other obesity-related comorbidities based on age. Finally, many reports now provide evidence that bariatric surgery can be safely performed in older subjects as the last treatment tier. Risk-benefit issues should be considered with extreme care and disclosed to candidates. The selection process requires good presurgical functional status, individualized consideration of the sequels of obesity and reliance on centers which are highly experienced in the surgical procedure as well as short and long term subsequent comprehensive care and support.
Impact of Obesity in Critical Illness.
Anderson Michaela R,Shashaty Michael G S
The prevalence of obesity is rising worldwide. Adipose tissue exerts anatomic and physiological effects with significant implications for critical illness. Changes in respiratory mechanics cause expiratory flow limitation, atelectasis, and V̇/Q̇ mismatch with resultant hypoxemia. Altered work of breathing and obesity hypoventilation syndrome may cause hypercapnia. Challenging mask ventilation and peri-intubation hypoxemia may complicate intubation. Patients with obesity are at increased risk of ARDS and should receive lung-protective ventilation based on predicted body weight. Increased positive end expiratory pressure (PEEP), coupled with appropriate patient positioning, may overcome the alveolar decruitment and intrinsic PEEP caused by elevated baseline pleural pressure; however, evidence is insufficient regarding the impact of high PEEP strategies on outcomes. Venovenous extracorporeal membrane oxygenation may be safely performed in patients with obesity. Fluid management should account for increased prevalence of chronic heart and kidney disease, expanded blood volume, and elevated acute kidney injury risk. Medication pharmacodynamics and pharmacokinetics may be altered by hydrophobic drug distribution to adipose depots and comorbid liver or kidney disease. Obesity is associated with increased risk of VTE and infection; appropriate dosing of prophylactic anticoagulation and early removal of indwelling catheters may decrease these risks. Obesity is associated with improved critical illness survival in some studies. It is unclear whether this reflects a protective effect or limitations inherent to observational research. Obesity is associated with increased risk of intubation and death in SARS-CoV-2 infection. Ongoing molecular studies of adipose tissue may deepen our understanding of how obesity impacts critical illness pathophysiology.
Curcumin analogue C66 attenuates obesity-induced myocardial injury by inhibiting JNK-mediated inflammation.
Ye Lin,Chen Xiaojun,Wang Minxiu,Jin Leiming,Zhuang Zaishou,Yang Daona,Guan Xinfu,Samorodov Aleksandr V,Pavlov Valentin N,Chattipakorn Nipon,Feng Jianpeng,Wang Yi,Luo Wu,Liang Guang
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
Obesity has been recognized as a major risk factor for the development of chronic cardiomyopathy, which is associated with increased cardiac inflammation, fibrosis, and apoptosis. We previously developed an anti-inflammatory compound C66, which prevented inflammatory diabetic complications via targeting JNK. In the present study, we have tested the hypothesis that C66 could prevent obesity-induced cardiomyopathy by suppressing JNK-mediated inflammation. High-fat diet (HFD)-induced obesity mouse model and palmitic acid (PA)-challenged H9c2 cells were used to develop inflammatory cardiomyopathy and evaluate the protective effects of C66. Our data demonstrate a protective effect of C66 against obesity-induced cardiac inflammation, cardiac hypertrophy, fibrosis, and dysfunction, overall providing cardio-protection. C66 administration attenuates HFD-induced myocardial inflammation by inhibiting NF-κB and JNK activation in mouse hearts. In vitro, C66 prevents PA-induced myocardial injury and apoptosis in H9c2 cells, accompanied with inhibition against PA-induced JNK/NF-κB activation and inflammation. The protective effect of C66 is attributed to its potential to inhibit JNK activation, which led to reduced pro-inflammatory cytokine production and reduced apoptosis in cardiomyocytes both in vitro and in vivo. In summary, C66 provides significant protection against obesity-induced cardiac dysfunction, mainly by inhibiting JNK activation and JNK-mediated inflammation. Our data indicate that inhibition of JNK is able to provide significant protection against obesity-induced cardiac dysfunction.
Obesity cardiomyopathy: evidence, mechanisms, and therapeutic implications.
The prevalence of heart failure is on the rise and imposes a major health threat, in part, due to the rapidly increased prevalence of overweight and obesity. To this point, epidemiological, clinical, and experimental evidence supports the existence of a unique disease entity termed "obesity cardiomyopathy," which develops independent of hypertension, coronary heart disease, and other heart diseases. Our contemporary review evaluates the evidence for this pathological condition, examines putative responsible mechanisms, and discusses therapeutic options for this disorder. Clinical findings have consolidated the presence of left ventricular dysfunction in obesity. Experimental investigations have uncovered pathophysiological changes in myocardial structure and function in genetically predisposed and diet-induced obesity. Indeed, contemporary evidence consolidates a wide array of cellular and molecular mechanisms underlying the etiology of obesity cardiomyopathy including adipose tissue dysfunction, systemic inflammation, metabolic disturbances (insulin resistance, abnormal glucose transport, spillover of free fatty acids, lipotoxicity, and amino acid derangement), altered intracellular especially mitochondrial Ca homeostasis, oxidative stress, autophagy/mitophagy defect, myocardial fibrosis, dampened coronary flow reserve, coronary microvascular disease (microangiopathy), and endothelial impairment. Given the important role of obesity in the increased risk of heart failure, especially that with preserved systolic function and the recent rises in COVID-19-associated cardiovascular mortality, this review should provide compelling evidence for the presence of obesity cardiomyopathy, independent of various comorbid conditions, underlying mechanisms, and offer new insights into potential therapeutic approaches (pharmacological and lifestyle modification) for the clinical management of obesity cardiomyopathy.
Mechanisms linking endoplasmic reticulum (ER) stress and microRNAs to adipose tissue dysfunction in obesity.
Menikdiwela Kalhara R,Tôrres Guimarães João Pedro,Ramalingam Latha,Kalupahana Nishan S,Dufour Jannette M,Washburn Rachel L,Moustaid-Moussa Naima
Critical reviews in biochemistry and molecular biology
Over accumulation of lipids in adipose tissue disrupts metabolic homeostasis by affecting cellular processes. Endoplasmic reticulum (ER) stress is one such process affected by obesity. Biochemical and physiological alterations in adipose tissue due to obesity interfere with adipose ER functions causing ER stress. This is in line with increased irregularities in other cellular processes such as inflammation and autophagy, affecting overall metabolic integrity within adipocytes. Additionally, microRNAs (miRNAs), which can post-transcriptionally regulate genes, are differentially modulated in obesity. A better understanding and identification of such miRNAs could be used as novel therapeutic targets to fight against diseases. In this review, we discuss ways in which ER stress participates as a common molecular process in the pathogenesis of obesity-associated metabolic disorders. Moreover, our review discusses detailed underlying mechanisms through which ER stress and miRNAs contribute to metabolic alteration in adipose tissue in obesity. Hence, identifying mechanistic involvement of miRNAs-ER stress cross-talk in regulating adipose function during obesity could be used as a potential therapeutic approach to combat chronic diseases, including obesity.
Obesity prevalence in celiac disease in the United States from 2014 to 2018.
International journal of obesity (2005)
Celiac disease (CD) is not commonly associated with obesity; however, many patients are overweight or obese at time of diagnosis. As the number of people in the United States with obesity continues to rise, it is not known if the prevalence of obesity among patients with CD has also increased. This study utilized an electronic health record database incorporating over 360 individual hospitals in the United States (Explorys Incorporated, Cleveland, OH). Adult patients who had an esophagogastroduodenoscopy at least 1 day prior to reporting of CD from the years 2014 to 2018 formed the study population. From 2014 to 2018, 13,410 patients had a diagnosis of CD. The prevalence of obesity was 45,000/100,000 persons in this CD population. Prevalence of class I (BMI 30-34.9), II (BMI 35-39.9), and III (BMI > 40) obesity in patients with CD continued to rise over the 5-year span. Class I obesity had the highest prevalence and Class II the highest prevalence increase when obesity classes were compared. Clinicians should be aware of obesity as a comorbidity of increasing prevalence when providing longitudinal care for patients with CD.
Economic impacts of overweight and obesity: current and future estimates for eight countries.
Okunogbe Adeyemi,Nugent Rachel,Spencer Garrison,Ralston Johanna,Wilding John
BMJ global health
BACKGROUND:Obesity is a growing public health challenge worldwide with significant health and economic impacts. However, much of what is known about the economic impacts of obesity comes from high-income countries and studies are not readily comparable due to methodological differences. Our objective is to demonstrate a method for estimating current and future national economic impacts of obesity and apply it across a sample of heterogeneous contexts globally. METHODS:We estimated economic impacts of overweight and obesity for eight countries using a cost-of-illness approach. Direct and indirect costs of obesity from 2019 to 2060 were estimated from a societal perspective as well as the effect of two hypothetical scenarios of obesity prevalence projections. Country-specific data were sourced from published studies and global databases. RESULTS:In per capita terms, costs of obesity in 2019 ranged from US$17 in India to US$940 in Australia. These economic costs are comparable to 1.8% of gross domestic product (GDP) on average across the eight countries, ranging from 0.8% of GDP in India to 2.4% in Saudi Arabia. By 2060, with no significant changes to the status quo, the economic impacts from obesity are projected to grow to 3.6% of GDP on average ranging from 2.4% of GDP in Spain to 4.9% of GDP in Thailand. Reducing obesity prevalence by 5% from projected levels or keeping it at 2019 levels will translate into an average annual reduction of 5.2% and 13.2% in economic costs, respectively, between 2020 and 2060 across the eight countries. CONCLUSION:Our findings demonstrate that the economic impacts of obesity are substantial across countries, irrespective of economic or geographical context and will increase over time if current trends continue. These findings strongly point to the need for advocacy to increase awareness of the societal impacts of obesity, and for policy actions to address the systemic roots of obesity.
Validation of obesity-related diagnosis codes in claims data.
Diabetes, obesity & metabolism
AIM:To determine whether body mass index (BMI) can be accurately identified in epidemiological studies using claims databases. MATERIALS AND METHODS:Using the Mass General Brigham Research Patient Data Repository-Medicare-linked database, we identified a cohort of patients with a BMI measurement for the periods January 1 to June 31, 2014 or January 1 to June 31, 2016, to capture both the International Classification of Disease (ICD)-9 and ICD-10 eras. Patients were divided into two groups, with or without an obesity-related ICD code in the 6 months before or after the BMI measurement date. We created two binary measures, first for composite overweight, obesity, or severe obesity (BMI ≥25 kg/m ), and second for obesity or severe obesity (BMI ≥30 kg/m ). We calculated accuracy measures (sensitivity, specificity, positive predictive value [PPV] and negative predictive value [NPV]) for each obesity category for the overall cohort, and stratified by type 2 diabetes and ICD-code era. RESULTS:The cohort included 73 644 patients with a BMI measurement in 2014 or 2016, of whom 16 280 had an obesity-related ICD code. The specificity of obesity-related ICD codes (ICD-9 and ICD-10) was 99.7% for underweight/normal weight, 97.4% for overweight, 99.7% for obese and 98.9% for severely obese. For binary categories capturing BMI ≥25 kg/m and BMI ≥30 kg/m , specificity was 97.0% and 98.2%, and PPV was 86.9% and 97.3%. Sensitivity was low overall (<40%). Codes for patients with type 2 diabetes and codes in the ICD-10 era had higher sensitivity, PPV and NPV. CONCLUSION:Obesity-related ICD codes can accurately identify patients with obesity in epidemiological studies using claims databases.
The role of the nurse in the Obesity Clinic: a practical guideline.
Barrea Luigi,Framondi Lydia,DI Matteo Rossana,Verde Ludovica,Vetrani Claudia,Graziadio Chiara,Pugliese Gabriella,Laudisio Daniela,Vitale Giovanni,Iannicelli Anna Maria,Savastano Silvia,Colao Annamaria,Muscogiuri Giovanna
Obesity is a major public health issue, and its trend is increasing worldwide. Interventions to effectively treat obesity and its related diseases are advocated. Given the complexity of obesity management, nurses need specific core skills to work in the Obesity Clinic and can act as key players in the multidisciplinary team of the Obesity Clinic. To provide practical guidelines for nurses working in Obesity Clinic for effective management of obesity and its related diseases, the current evidence on the role nurses in the obesity clinic was reviewed. Nurses can play a pivotal role in the management of patients with obesity and associated diseases that may require a stricter follow-up than usual care. Given the complexity of the treatment of obesity and its comorbidity, nurses should receive a specific training for: 1) methods and tools to effectively treat obesity and obesity-related disease; 2) patients and families education on nutrition, lifestyle changes, and prevention/management of obesity-related diseases; 3) motivation of patients towards adherence to treatment to achieve their specific goals. This review highlights the need of specific core skills for nurses working in the Obesity Clinic.
The genetics of obesity: from discovery to biology.
Nature reviews. Genetics
The prevalence of obesity has tripled over the past four decades, imposing an enormous burden on people's health. Polygenic (or common) obesity and rare, severe, early-onset monogenic obesity are often polarized as distinct diseases. However, gene discovery studies for both forms of obesity show that they have shared genetic and biological underpinnings, pointing to a key role for the brain in the control of body weight. Genome-wide association studies (GWAS) with increasing sample sizes and advances in sequencing technology are the main drivers behind a recent flurry of new discoveries. However, it is the post-GWAS, cross-disciplinary collaborations, which combine new omics technologies and analytical approaches, that have started to facilitate translation of genetic loci into meaningful biology and new avenues for treatment.
Endoscopic Approaches to Obesity Management.
Dolan Russell D,Schulman Allison R
Annual review of medicine
The field of endoscopic bariatric and metabolic therapy has rapidly evolved from offering endoscopic treatment of weight regain following bariatric surgery to providing primary weight loss options as alternatives to pharmacologic and surgical interventions. Gastric devices and remodeling procedures were initially designed to work through a mechanism of volume restriction, leading to earlier satiety and reduced caloric intake. As the field continues to grow, small bowel interventions are evolving that may have some effect on weight loss but focus on the treatment of obesity-related comorbidities. Future implementation of combination therapy that utilizes both gastric and small bowel interventions offers an exciting option to further augment weight loss and alleviate metabolic disease. This review considers gastric devices and techniques including space-occupying intragastric balloons, aspiration therapy, endoscopic tissue suturing, and plication interventions, followed by a review of small bowel interventions including endoluminal bypass liners, duodenal mucosal resurfacing, and endoscopically delivered devices to create incisionless anastomoses.
White adipose tissue dysfunction in obesity and aging.
Reyes-Farias Marjorie,Fos-Domenech Julia,Serra Dolors,Herrero Laura,Sánchez-Infantes David
Both obesity and aging are associated with the development of metabolic diseases such as type 2 diabetes and cardiovascular disease. Chronic low-grade inflammation of adipose tissue is one of the mechanisms implicated in the progression of these diseases. Obesity and aging trigger adipose tissue alterations that ultimately lead to a pro-inflammatory phenotype of the adipose tissue-resident immune cells. Obesity and aging also share other features such as a higher visceral vs. subcutaneous adipose tissue ratio and a decreased lifespan. Here, we review the common characteristics of obesity and aging and the alterations in white adipose tissue and resident immune cells. We focus on the adipose tissue metabolic derangements in obesity and aging such as inflammation and adipose tissue remodeling.
Homeostasis and food craving in obesity: a functional MRI study.
International journal of obesity (2005)
OBJECTIVES:Food intake in obesity has been found to be reward-based and less contingent on homeostatic needs. Accordingly, previous studies investigating neural processing of food cues observed aberrant processing in reward- and control-related brain regions in obesity. To further investigate the relation between homeostasis and food intake, this study investigated the influence of glucose metabolism on the neuronal response during the regulation of food craving in participants with obesity. METHODS:Twenty-five normal-weight and 25 women with obesity were examined on two occasions after receiving either water or glucose directly into the stomach using a nasogastric tube. Participants were blinded to the type of infusion and were required to refrain from eating for 16 h before each visit. An event-related fMRI paradigm was used to investigate the effect of intestinal glucose load on the neuronal response during the regulation of food craving. RESULTS:A 2 × 2 mixed-model ANOVA revealed that craving regulation was associated with increased activation in fronto-parietal regions in participants with obesity when compared to healthy controls. However, this effect was observed independently from homeostatic satiety. A regression analysis revealed that the reduction of food craving was related to increased activation in the lingual gyrus in individuals with obesity following the infusion of water. CONCLUSIONS:In participants with obesity, the neuronal response during the regulation of food craving is associated with increased neural cognitive top-down control and increased visual food processing. Since this observation was independent from satiety status, our results indicate a reduced influence of homeostasis on neural processing during food craving in obesity. This study was registered on clinicaltrials.org: NCT03075371.
Extracellular vesicles in obesity and its associated inflammation.
International reviews of immunology
Obesity is characterized by low-grade, chronic inflammation, which promotes insulin resistance and diabetes. Obesity can lead to the development and progression of many autoimmune diseases, including inflammatory bowel disease, psoriasis, psoriatic arthritis, rheumatoid arthritis, thyroid autoimmunity, and type 1 diabetes mellitus (T1DM). These diseases result from an alteration of self-tolerance by promoting pro-inflammatory immune response by lowering numbers of regulatory T cells (), increasing Th1 and Th17 immune responses, and inflammatory cytokine production. Therefore, understanding the immunological changes that lead to this low-grade inflammatory milieu becomes crucial for the development of therapies that suppress the risk of autoimmune diseases and other immunological conditions. Cells generate extracellular vesicles (EVs) to eliminate cellular waste as well as communicating the adjacent and distant cells through exchanging the components (genetic material [DNA or RNA], lipids, and proteins) between them. Immune cells and adipocytes from individuals with obesity and a high basal metabolic index (BMI) produce also release exosomes (EXOs) and microvesicles (MVs), which are collectively called EVs. These EVs play a crucial role in the development of autoimmune diseases. The current review discusses the immunological dysregulation that leads to inflammation, inflammatory diseases associated with obesity, and the role played by EXOs and MVs in the induction and progression of this devastating conditi8on.
Future directions in obesity pharmacotherapy.
European journal of internal medicine
There is a growing unmet need for more effective treatment of obesity and its complications. While current anti-obesity medications are effective and offer real clinical benefits over diet and lifestyle interventions, they cannot meet the levels of efficacy and reduction of hard endpoint outcomes seen with bariatric surgery. As knowledge on the control of body weight unravels, the complexity of this physiology opens the opportunity to new druggable targets. Currently, gut peptide analogues such as semaglutide, a glucagon like peptide-1 (GLP-1) receptor agonist, and the dual agonist GLP-1 and gastric inhibitory polypeptide (GIP) tirzepatide are the furthest advanced in clinical development and seem likely to meet current regulatory requirements within the next year or so. However, current regulatory requirements are out of step with the efficacy of new compounds and concepts relating to obesity and its complications. Many other drugs in early development will target different pathways of energy balance, raising the possibility of drug combinations to maximise efficacy as for other chronic disease such as hypertension and diabetes. This will allow more complex and personalised guidelines to evolve.
The lived experience of patients with obesity: A systematic review and qualitative synthesis.
Farrell Emma,Hollmann Eva,le Roux Carel W,Bustillo Marta,Nadglowski Joe,McGillicuddy Deirdre
Obesity reviews : an official journal of the International Association for the Study of Obesity
Although the deleterious effects of obesity have been well documented in terms of morbidity and mortality, less is known about what it is like to live with this complex and chronic disease. This study systematically reviewed and synthesized peer-reviewed studies relating to the lived experience of patients with obesity. A total of 12,388 records were screened, resulting in the inclusion of 32 final studies. Meta-ethnographic synthesis of these 32 studies generated five "third-order constructs" or themes: the development of obesity; a life limited; stigma, judgment, shame, and blame; treatment and; experiences of specific or minority groups. These constructs describe, from the patient's perspective, the factors associated with the development and maintenance of obesity; the effects of the disease on their day-to-day lives; the impact of the stigma and judgment many patients are subjected to; and their experience of accessing, or trying to access, treatment for their healthcare needs. This synthesis reveals the dearth of studies that focus solely on the experience of the patient and highlights the tendency for participant-informed, rather than participatory, methods in obesity research. It concludes with a call for further participatory research into the experiences of people living with obesity.
LRG1 is an adipokine that mediates obesity-induced hepatosteatosis and insulin resistance.
The Journal of clinical investigation
Dysregulation in adipokine biosynthesis and function contributes to obesity-induced metabolic diseases. However, the identities and functions of many of the obesity-induced secretory molecules remain unknown. Here, we report the identification of leucine-rich alpha-2-glycoprotein 1 (LRG1) as an obesity-associated adipokine that exacerbates high fat diet-induced hepatosteatosis and insulin resistance. Serum levels of LRG1 were markedly elevated in obese humans and mice compared with their respective controls. LRG1 deficiency in mice greatly alleviated diet-induced hepatosteatosis, obesity, and insulin resistance. Mechanistically, LRG1 bound with high selectivity to the liver and promoted hepatosteatosis by increasing de novo lipogenesis and suppressing fatty acid β-oxidation. LRG1 also inhibited hepatic insulin signaling by downregulating insulin receptor substrates 1 and 2. Our study identified LRG1 as a key molecule that mediates the crosstalk between adipocytes and hepatocytes in diet-induced hepatosteatosis and insulin resistance. Suppressing LRG1 expression and function may be a promising strategy for the treatment of obesity-related metabolic diseases.
Obesity Phenotypes and Electrocardiographic Characteristics in Physically Active Males: CHIEF Study.
Lin Yu-Kai,Tsai Kun-Zhe,Han Chih-Lu,Lin Yen-Po,Lee Jiunn-Tay,Lin Gen-Min
Frontiers in cardiovascular medicine
Metabolically unhealthy obesity (MUO) has been associated with surface electrocardiographic (ECG) left ventricular hypertrophy (LVH), left atrial enlargement (LAE), and inferior wave inversions (TWI) in the middle- and old-aged populations. However, the relationship between obesity phenotypes and these ECG abnormalities in physically active young adults is yet to be determined. A total of 2,156 physically active military males aged 18-50 in Taiwan were analyzed. Obesity and metabolically unhealthy status were, respectively, defined as the body mass index ≥27 kg/m and the presence of metabolic syndrome based on the ATPIII criteria for Asian male adults. Four groups were classified as the metabolically healthy non-obesity (MHNO, = 1,484), metabolically unhealthy non-obesity (MUNO, = 86), metabolically healthy obesity (MHO, = 376), and MUO ( = 210). ECG-LVH was based on the Sokolow-Lyon and Cornell voltage criteria, ECG-LAE was defined as a notched wave ≥0.12 s in lead II or a notch of ≥0.04 s, and inferior TWI was defined as one negative wave axis in limb leads II, III, or aVF. Physical performance was evaluated by time for a 3-km run. Multiple logistic regression analysis with adjustment for age, smoking, alcohol drinking, and physical performance was utilized to investigate the associations between obesity phenotypes and the ECG abnormalities. As compared to MHNO, MUNO, MHO, and MUO were associated with lower risk of Sokolow-Lyon-based ECG-LVH [odds ratios (OR) and 95% confidence intervals: 0.80 (0.51-1.25), 0.46 (0.36-0.58), and 0.39 (0.28-0.53), respectively; for trend <0.001], and with greater risk of ECG-LAE [OR: 0.87 (0.44-1.72), 2.34 (1.77-3.10), and 3.02 (2.13-4.28), respectively; for trend <0.001] and inferior TWI [OR: 2.21 (0.74-6.58), 3.49 (1.97-6.19), and 4.52 (2.38-8.60), respectively; for trend <0.001]. However, no associations between obesity phenotypes and Cornell-based ECG-LVH were found. In physically active young males, obesity was associated with higher risk of ECG-LAE and inferior TWI, whereas the risk between obesity and ECG-LVH might vary by the ECG criteria, possibly due to a high prevalence of exercise induced-LVH in military and greater chest wall thickness in obesity. The cardiovascular prognosis of ECG-LVH in physically active obese adults requires further study.
Alternative Mitophagy Protects the Heart Against Obesity-Associated Cardiomyopathy.
RATIONALE:Obesity-associated cardiomyopathy characterized by hypertrophy and mitochondrial dysfunction. Mitochondrial quality control mechanisms, including mitophagy, are essential for the maintenance of cardiac function in obesity-associated cardiomyopathy. However, autophagic flux peaks at around 6 weeks of high-fat diet (HFD) consumption and declines thereafter. OBJECTIVE:We investigated whether mitophagy is activated during the chronic phase of cardiomyopathy associated with obesity (obesity cardiomyopathy) after general autophagy is downregulated and, if so, what the underlying mechanism and the functional significance are. METHODS AND RESULTS:Mice were fed either a normal diet or a HFD (60 kcal% fat). Mitophagy, evaluated using Mito-Keima, was increased after 3 weeks of HFD consumption and continued to increase after conventional mechanisms of autophagy were inactivated, at least until 24 weeks. HFD consumption time-dependently upregulated both Ser555-phosphorylated Ulk1 (unc-51 like kinase 1) and Rab9 (Ras-related protein Rab-9) in the mitochondrial fraction. Mitochondria were sequestrated by Rab9-positive ring-like structures in cardiomyocytes isolated from mice after 20 weeks of HFD consumption, consistent with the activation of alternative mitophagy. Increases in mitophagy induced by HFD consumption for 20 weeks were abolished in cardiac-specific knockout mouse hearts, in which both diastolic and systolic dysfunction were exacerbated. Rab9 S179A knock-in mice, in which alternative mitophagy is selectively suppressed, exhibited impaired mitophagy and more severe cardiac dysfunction than control mice following HFD consumption for 20 weeks. Overexpression of Rab9 in the heart increased mitophagy and protected against cardiac dysfunction during HFD consumption. HFD-induced activation of Rab9-dependent mitophagy was accompanied by upregulation of TFE3 (transcription factor binding to IGHM enhancer 3), which plays an essential role in transcriptional activation of mitophagy. CONCLUSIONS:Ulk1-Rab9-dependent alternative mitophagy is activated during the chronic phase of HFD consumption and serves as an essential mitochondrial quality control mechanism, thereby protecting the heart against obesity cardiomyopathy.
Impact of Morbid Obesity and Obesity Phenotype on Outcomes After Transcatheter Aortic Valve Replacement.
McInerney Angela,Tirado-Conte Gabriela,Rodes-Cabau Josep,Campelo-Parada Francisco,Tafur Soto Jose D,Barbanti Marco,Muñoz-Garcia Erika,Arif Mobeena,Lopez Diego,Toggweiler Stefan,Veiga Gabriela,Pylko Anna,Sevilla Teresa,Compagnone Miriam,Regueiro Ander,Serra Viçent,Carnero Manuel,Oteo Juan F,Rivero Fernando,Barbosa Ribeiro Henrique,Guimaraes Leonardo,Matta Anthony,Giraldo Echavarria Natalia,Valvo Roberto,Moccetti Federico,Muñoz-Garcia Antonio J,Lopez-Pais Javier,Garcia Del Blanco Bruno,Campanha Borges Diego Carter,Dumont Eric,Gonzalo Nieves,Criscione Enrico,Dabrowski Maciej,Alfonso Fernando,de la Torre Hernández Jose M,Cheema Asim N,Amat-Santos Ignacio J,Saia Francesco,Escaned Javier,Nombela-Franco Luis
Journal of the American Heart Association
Background There is a paucity of outcome data on patients who are morbidly obese (MO) undergoing transcatheter aortic valve replacement. We aimed to determine their periprocedural and midterm outcomes and investigate the impact of obesity phenotype. Methods and Results Consecutive patients who are MO (body mass index, ≥40 kg/m, or ≥35 kg/m with obesity-related comorbidities; n=910) with severe aortic stenosis who underwent transcatheter aortic valve replacement in 18 tertiary hospitals were compared with a nonobese cohort (body mass index, 18.5-29.9 kg/m, n=2264). Propensity-score matching resulted in 770 pairs. Pre-transcatheter aortic valve replacement computed tomography scans were centrally analyzed to assess adipose tissue distribution; epicardial, abdominal visceral and subcutaneous fat. Major vascular complications were more common (6.6% versus 4.3%; =0.043) and device success was less frequent (84.4% versus 88.1%; =0.038) in the MO group. Freedom from all-cause and cardiovascular mortality were similar at 2 years (79.4 versus 80.6%, =0.731; and 88.7 versus 87.4%, =0.699; MO and nonobese, respectively). Multivariable analysis identified baseline glomerular filtration rate and nontransfemoral access as independent predictors of 2-year mortality in the MO group. An adverse MO phenotype with an abdominal visceral adipose tissue:subcutaneous adipose tissue ratio ≥1 (VAT:SAT) was associated with increased 2-year all-cause (hazard ratio [HR], 3.06; 95% CI, 1.20-7.77; =0.019) and cardiovascular (hazard ratio, 4.11; 95% CI, 1.06-15.90; =0.041) mortality, and readmissions (HR, 1.81; 95% CI, 1.07-3.07; =0.027). After multivariable analysis, a (VAT:SAT) ratio ≥1 remained a strong predictor of 2-year mortality (hazard ratio, 2.78; =0.035). Conclusions Transcatheter aortic valve replacement in patients who are MO has similar short- and midterm outcomes to nonobese patients, despite higher major vascular complications and lower device success. An abdominal VAT:SAT ratio ≥1 identifies an obesity phenotype at higher risk of adverse clinical outcomes.
Hypothalamic endocannabinoids in obesity: an old story with new challenges.
Cellular and molecular life sciences : CMLS
The crucial role of the hypothalamus in the pathogenesis of obesity is widely recognized, while the precise molecular and cellular mechanisms involved are the focus of intense research. A disrupted endocannabinoid system, which critically modulates feeding and metabolic functions, through central and peripheral mechanisms, is a landmark indicator of obesity, as corroborated by investigations centered on the cannabinoid receptor CB1, considered to offer promise in terms of pharmacologically targeted treatment for obesity. In recent years, novel insights have been obtained, not only into relation to the mode of action of CB receptors, but also CB ligands, non-CB receptors, and metabolizing enzymes considered to be part of the endocannabinoid system (particularly the hypothalamus). The outcome has been a substantial expansion in knowledge of this complex signaling system and in drug development. Here we review recent literature, providing further evidence on the role of hypothalamic endocannabinoids in regulating energy balance and the implication for the pathophysiology of obesity. We discuss how these lipids are dynamically regulated in obesity onset, by diet and metabolic hormones in specific hypothalamic neurons, the impact of gender, and the role of endocannabinoid metabolizing enzymes as promising targets for tackling obesity and related diseases.
Nuclear Receptors and Transcription Factors in Obesity-Related Kidney Disease.
Seminars in nephrology
Both obesity and chronic kidney disease are increasingly common causes of morbidity and mortality worldwide. Although obesity often co-exists with diabetes and hypertension, it has become clear over the past several decades that obesity is an independent cause of chronic kidney disease, termed obesity-related glomerulopathy. This review defines the attributes of obesity-related glomerulopathy and describes potential pharmacologic interventions. Interventions discussed include peroxisome proliferator-activated receptors, the farnesoid X receptor, the Takeda G-protein-coupled receptor 5, and the vitamin D receptor.
Approach to Obesity in the Older Population.
The Journal of clinical endocrinology and metabolism
Until recently, weight loss in older obese people was feared because of ensuing muscle loss and frailty. Facing overall increasing longevity, high rates of obesity in older individuals (age ≥ 65 years) and a growing recognition of the health and functional cost of the number of obesity years, abetted by evidence that intentional weight loss in older obese people is safe, this approach is gradually, but not unanimously, being replaced by more active principles. Lifestyle interventions that include reduced but sufficient energy intake, age-adequate protein and micronutrient intake, coupled with aerobic and resistance exercise tailored to personal limitations, can induce weight loss with improvement in frailty indices. Sustained weight loss at this age can prevent or ameliorate diabetes. More active steps are controversial. The use of weight loss medications, particularly glucagon-like peptide-1 analogs (liraglutide as the first example), provides an additional treatment tier. Its safety and cardiovascular health benefits have been convincingly shown in older obese patients with type 2 diabetes mellitus. In our opinion, this option should not be denied to obese individuals with prediabetes or other obesity-related comorbidities based on age. Finally, many reports now provide evidence that bariatric surgery can be safely performed in older people as the last treatment tier. Risk-benefit issues should be considered with extreme care and disclosed to candidates. The selection process requires good presurgical functional status, individualized consideration of the sequels of obesity, and reliance on centers that are highly experienced in the surgical procedure as well as short-term and long-term subsequent comprehensive care and support.
The Renal Pathology of Obesity: Structure-Function Correlations.
Tsuboi Nobuo,Okabayashi Yusuke
Seminars in nephrology
The kidney is one of the target organs that may show health disorders as a result of obesity. Obesity-related glomerulopathy (ORG) is a kidney disease category based on a biopsy diagnosis that may occur secondary to obesity. Detailed clinicopathologic observations of ORG have provided significant knowledge regarding obesity-associated renal complications. Glomerulomegaly with focal segmental glomerulosclerosis of perihilar locations is a typical renal histopathologic finding in ORG, which has long been considered to represent a state of single-nephron glomerular hyperfiltration. This hypothesis was recently confirmed in ORG patients by estimating single-nephron glomerular filtration rate using a combined image analysis and biopsy-based stereology. Overshooting in glomerulotubular and tubuloglomerular interactions may lead to glomerular hyperfiltration/hypertension, podocyte failure, tubular protein-traffic overload, and tubulointerstitial scarring, constituting a vicious cycle of a common pathway to the further loss of functioning nephrons and the progression of kidney functional impairment.
Renal Cellular Autophagy in Obesity: Boon or Bane?
Seminars in nephrology
Obesity is a growing human health concern worldwide and imposes adverse effects on many cell types and organ systems, including the kidneys. Obesity interferes with various cellular processes by increasing lipid accumulation and oxidation, insulin resistance, and inflammation. Autophagy is an important cellular process to maintain hemostasis and preserve resources, but might be altered in obesity. Interestingly, experimental studies have shown either an increase or a decrease in the rate of autophagy, and accumulation of byproducts and mediators of this cascade in kidneys of obese individuals. Hence, whether autophagy is beneficial or detrimental under these conditions remains unresolved. This review summarizes emerging evidence linking superfluous fat accumulation to alterations in autophagy. Elucidating the role of autophagy in the pathogenesis and complications of obesity in the kidney might help in the identification of therapeutic targets to prevent or delay the development of chronic kidney disease in obese subjects. Autophagy, kidney, obesity, lipids.
Obesity Management and Chronic Kidney Disease.
Chen Yang,Dabbas Walaa,Gangemi Antonio,Benedetti Enrico,Lash James,Finn Patricia W,Perkins David L
Seminars in nephrology
Obesity is one of the risk factors for the development and progression of chronic kidney disease (CKD). Several studies have shown the association between increased body mass index and kidney function decline. Obesity leads to CKD directly by acting as an independent risk factor and indirectly through increasing risks for diabetes, hypertension, and atherosclerosis, a group of well-established independent risk factors for CKD. Alterations in renal hemodynamics, inflammation, and in hormones and growth factors results in hyperfiltration injury and focal segmental glomerulosclerosis. In recent years, many studies have shown that the gut microbiome may play a role in the pathogenesis of obesity. Dysbiosis has been noted in obese subjects in both human and animal studies. Changes in the gut microbiome in obese patients promote weight gain by effectively extracting energy from diet, and induction of low-grade inflammation. Evidence also points to the role of inflammation within the adipose tissue in obesity as a key factor in the pathogenesis of obesity-related complications. Thus, obesity is the net result of complex interactions between behavioral, genetic, and environmental factors. In terms of management, conservative approaches are often the first option, but they often are unsuccessful in achieving and/or maintaining weight loss, particularly in severe obesity. Consequently, nonmedical management with bariatric surgery is the most effective treatment option for morbid obesity and has shown mitigation of multiple risk factors for the progression of CKD. The most frequently performed interventions are vertical sleeve gastrectomy and Roux-en-Y gastric bypass. Studies have shown that bariatric surgery is associated with beneficial effects on CKD by mitigating its risk factors by weight loss, reducing insulin resistance, hemoglobin A1c, and proteinuria, in addition to positive long-term outcomes. Because of the epidemic of obesity, the prevalence of obesity in kidney transplant recipients also is increasing. The maximal body mass index (BMI) threshold for kidney transplantation is not clear. The Organ Procurement Transplant Network/Scientific Registry of Transplant Recipients 2019 annual data report showed that the proportion of kidney transplant recipient candidates with a BMI of 30 kg/m or greater is increasing steadily. Morbid obesity is linked to adverse graft outcomes including delayed graft function, primary nonfunction, and decreased graft survival. Obesity is also an independent risk factor for cardiovascular death in kidney transplant recipients, suggesting that these patients should not be excluded from transplantation based on their BMI because transplantation is associated with lower mortality compared with dialysis. However, many centers exclude obese patients (with different BMI cut-off values) from transplantation to avoid postoperative complications. To minimize the surgical complications of kidney transplantation in obese patients, our center has adopted the robot-assisted kidney transplantation procedure. Our data show that this approach is comparable with historical nonobese controls in the United Network for Organ Sharing database in terms of patient and graft survival. Another surgical option for this group of patients at our center is a combined robotic sleeve gastrectomy and robotic-assisted kidney transplant. In a recent study, this approach showed promising results in terms of weight loss, patient survival, and graft survival, and might become more common in the future.
Podocytopathy in Obesity: Challenges of Living Large.
Giannini Gabriel,Kopp Jeffrey B,Rosenberg Avi Z
Seminars in nephrology
Renal injury resulting from obesity is a growing concern caused by the global obesity epidemic. We discuss the glomerular structure, obesity-related glomerular changes, and diagnostic pathologic criteria for obesity-related glomerulopathy. The three main hypothesized mechanisms of podocyte injury are mechanical stress on the podocytes, metabolic derangement, and genetic/molecular factors. Weight loss, renin-angiotensin-aldosterone system inhibitors, and improved insulin resistance may slow the progression. A more comprehensive understanding of obesity-related glomerulopathy will help in developing more effective therapies.
Obesity-Related Glomerulopathy: Clinical Management.
Herman-Edelstein Michal,Weinstein Talia,Chagnac Avry
Seminars in nephrology
Obesity-related glomerulopathy (ORG) and other obesity-associated kidney diseases pose a major challenge to the treating nephrologist. We review the benefits of weight loss and optimal management of ORG and kidney disease in the setting of obesity. Therapeutic strategies in ORG were limited mainly in the past to weight loss through lifestyle interventions and bariatric surgery, antihypertensive treatment, and renin-angiotensin-aldosterone system blockade. Current approaches to obtain the desired weight loss include novel pharmacologic therapies that have been approved for the treatment of diabetes while offering kidney protection, such as sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1-receptor agonists. This review focuses on the nephroprotective role of the renin-angiotensin-aldosterone system blockade and of these new pharmacologic agents, and on the renal effects of bariatric surgery in chronic kidney disease.
The incretin/glucagon system as a target for pharmacotherapy of obesity.
Obesity reviews : an official journal of the International Association for the Study of Obesity
Obesity is a chronic, multifactorial, relapsing disease. Despite multicomponent lifestyle interventions, including pharmacotherapy, maintaining bodyweight loss is challenging for many people. The pathophysiology of obesity is complex, and currently approved pharmacotherapies only target a few of the many pathways involved; thus, single-targeting agents have limited efficacy. Proglucagon-derived peptides, glucagon, and the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), represent attractive targets for managing obesity and metabolic disorders because they may have direct roles in multiple mechanisms including satiety, energy homeostasis, and lipolytic activity. Unimolecular dual and triple agonists targeting glucagon and incretin hormone receptors have been shown to promote bodyweight loss, lower glucose levels, and reduce food intake in animal models of obesity. Multiple dual receptor agonists are in clinical development for the treatment of obesity, including GLP-1/GIP and GLP-1/glucagon receptor agonists. The extent to which glucagon contributes to treatment effects remains to be understood, but it may promote bodyweight loss by reducing food intake, while concomitant GLP-1 receptor agonism ensures normal glucose control. Further research is required to fully understand the molecular mechanisms of action and metabolic effects of both dual and triple receptor agonists.
Protein acetylation: a novel modus of obesity regulation.
Liu Yuexia,Yang Hong,Liu Xuanchen,Gu Huihui,Li Yizhou,Sun Chao
Journal of molecular medicine (Berlin, Germany)
Obesity is a chronic epidemic disease worldwide which has become one of the important public health issues. It is a process that excessive accumulation of adipose tissue caused by long-term energy intake exceeding energy expenditure. So far, the prevention and treatment strategies of obesity on individuals and population have not been successful in the long term. Acetylation is one of the most common ways of protein post-translational modification (PTM). It exists on thousands of non-histone proteins in almost every cell chamber. It has many influences on protein levels and metabolome levels, which is involved in a variety of metabolic reactions, including sugar metabolism, tricarboxylic acid cycle, and fatty acid metabolism, which are closely related to biological activities. Studies have shown that protein acetylation levels are dynamically regulated by lysine acetyltransferases (KATs) and lysine deacetylases (KDACs). Protein acetylation modifies protein-protein and protein-DNA interactions and regulates the activity of enzymes or cytokines which is related to obesity in order to participate in the occurrence and treatment of obesity-related metabolic diseases. Therefore, we speculated that acetylation was likely to become effective means of controlling obesity in the future. In consequence, this review focuses on the mechanisms of protein acetylation controlled obesity, to provide theoretical basis for controlling obesity and curing obesity-related diseases, which is a significance for regulating obesity in the future. This review will focus on the role of protein acetylation in controlling obesity.
Educational attainment of offspring and obesity among older adults in China.
Li Yaoyue,Wang Guixin,Li Guofeng
Social science & medicine (1982)
The study focuses on the role of adult offspring's educational attainment in obesity among older adults in China and investigates age and birth cohort heterogeneities in the educational effect. Using the longitudinal data from the 1993-2015 China Health and Nutrition Survey (CHNS), we employed three-level mixed-effects models and conducted sex-stratified analyses to examine the effects of co-resident offspring's education on body mass index (BMI), overweight, waist circumference (WC), and abdominal obesity among older people born before 1956. After controlling for confounding factors, the overall results showed inverted U-shaped educational gradients in BMI-based outcomes for males and positive gradients for females. The effect of education on WC exhibited an inverted U-shaped pattern for both sexes, but no significant effect on abdominal obesity was found among the overall population. However, further analyses of interaction effects indicated considerable age and cohort variations in the educational effects on obesity outcomes. Offspring's schooling was positively associated with obesity among earlier birth cohorts; Among more recent birth cohorts, especially among females, the educational effects were reversed, and disparities in obesity outcomes across education categories strengthened with age. These findings imply that offspring's education appears to gradually exert a protective role against obesity among Chinese older adults in successive cohorts.
Obesity in Latin America, a scoping review of public health prevention strategies and an overview of their impact on obesity prevention.
Palacios Cristina,Magnus Marcia,Arrieta Alejandro,Gallardo Héctor,Tapia Roberto,Espinal Carlos
Public health nutrition
OBJECTIVE:To describe the strategies implemented in seventeen Latin American countries for obesity prevention and to provide an overview of their impact. DESIGN:A thorough search of strategies and their impact was done through an Internet search, governmental webpages, reports and research articles in English, Spanish and Portuguese. SETTING:Latin America (not including the Caribbean countries). PARTICIPANTS:Any. RESULTS:The Ministry of Health is the main oversight for obesity prevention, with six countries having a specific structure for this. Regular obesity monitoring occurs in a few countries, and thirteen countries have a national obesity prevention plan. The main regulations being implemented/designed are front-of-package labelling (sixteen countries), school environment (fifteen countries), school nutrition education (nine countries), promotion of physical activity level (nine countries) and sugar-sweetened beverage tax (eight countries). All countries have dietary guidelines. The main community-based programmes being implemented are school meals (seventeen countries), complementary nutrition (eleven countries), nutrition education (fourteen countries), promotion of physical activity (nine countries) and healthy environments (nine countries). Most of these strategies have not been evaluated. The few with positive results have used a coordinated, multi-disciplinary and multi-sector approach, with legislation and executive-level support. CONCLUSIONS:Important obesity prevention strategies are being implemented in the seventeen Latin American countries included in the present review. However, few have been evaluated to assess their impact on preventing obesity. This information can help assess that actions can be generalised to other countries within the region and can help inform how to prevent obesity in different settings.
Adaptive immune cells shape obesity-associated type 2 diabetes mellitus and less prominent comorbidities.
Nature reviews. Endocrinology
Obesity and type 2 diabetes mellitus (T2DM) are increasing in prevalence owing to decreases in physical activity levels and a shift to diets that include addictive and/or high-calorie foods. These changes are associated with the adoption of modern lifestyles and the presence of an obesogenic environment, which have resulted in alterations to metabolism, adaptive immunity and endocrine regulation. The size and quality of adipose tissue depots in obesity, including the adipose tissue immune compartment, are critical determinants of overall health. In obesity, chronic low-grade inflammation can occur in adipose tissue that can progress to systemic inflammation; this inflammation contributes to the development of insulin resistance, T2DM and other comorbidities. An improved understanding of adaptive immune cell dysregulation that occurs during obesity and its associated metabolic comorbidities, with an appreciation of sex differences, will be critical for repurposing or developing immunomodulatory therapies to treat obesity and/or T2DM-associated inflammation. This Review critically discusses how activation and metabolic reprogramming of lymphocytes, that is, T cells and B cells, triggers the onset, development and progression of obesity and T2DM. We also consider the role of immunity in under-appreciated comorbidities of obesity and/or T2DM, such as oral cavity inflammation, neuroinflammation in Alzheimer disease and gut microbiome dysbiosis. Finally, we discuss previous clinical trials of anti-inflammatory medications in T2DM and consider the path forward.
Effects and mechanisms of tea on obesity.
Critical reviews in food science and nutrition
Obesity has become a global health concern. It increases the risk of several diseases, such as type 2 diabetes mellitus, nonalcoholic fatty liver disease, and certain cancers, which threatens human health and increases social economic burden. As one of the most consumed beverages, tea contains various phytochemicals with potent bioactive properties and health-promoting effects, such as antioxidant, immune-regulation, cardiovascular protection and anticancer. Tea and its components are also considered as potential candidates for anti-obesity. Epidemiological studies indicate that regular consumption of tea is beneficial for reducing body fat. In addition, the experimental studies demonstrate that the potential anti-obesity mechanisms of tea are mainly involved in increasing energy expenditure and lipid catabolism, decreasing nutrient digestion and absorption as well as lipid synthesis, and regulating adipocytes, neuroendocrine system and gut microbiota. Moreover, most of clinical studies illustrate that the intake of green tea could reduce body weight and alleviate the obesity. In this review, we focus on the effect of tea and its components on obesity from epidemiological, experimental, and clinical studies, and discuss their potential mechanisms.
Contextualising Eating Disorder Concerns for Paediatric Obesity Treatment.
Lister Natalie B,Baur Louise A,Paxton Susan J,Jebeile Hiba
Current obesity reports
PURPOSE OF REVIEW:Eating disorders are complex mental health conditions that share risk factors with obesity. This review outlines the context for concerns that paediatric obesity treatment presents a risk for eating disorder development. RECENT FINDINGS:Most children and adolescents undergoing professionally supervised obesity treatment will have improvements or no change to eating disorder risk profiles. However, some may subsequently develop a clinical eating disorder, and this is proposed to relate to weight-focussed dietary interventions that are standard in paediatric obesity treatment. Nevertheless, dietary restraint may not be a strong predictor of eating disorder risk in the context of paediatric obesity treatment. Most international guidelines recommend weight maintenance or weight loss as a treatment goal, and weight loss is related to improvements in cardiometabolic health but not eating disorder risk in the short term. The risk of inducing or exacerbating an eating disorder during paediatric weight management is likely to be low; however, the serious consequences combined with increasing scale of obesity treatment, and lack of empirical evidence, are of concern. There is a need for further research to identify long-term predictors of eating disorder development for children and adolescents who seek treatment for their obesity.
Treating the Chronic Disease of Obesity.
Gossmann Mona,Butsch W Scott,Jastreboff Ania M
The Medical clinics of North America
Obesity is a treatable chronic disease. Primary care providers play an essential role in diagnosis, treatment, and comprehensive care of patients with obesity. In recent years, treatment approaches have rapidly evolved, increasing effective and safe therapies. In this review, we provide practical information on the care of patients with obesity with a focus on antiobesity pharmacotherapy within the context of currently available therapeutic modalities such as intensive lifestyle interventions and bariatric surgery.
Obesity, Senescence, and Senolytics.
Handbook of experimental pharmacology
Obesity is a major risk factor for the development of comorbidities such as type 2 diabetes, neurodegenerative disorders, osteoarthritis, cancer, cardiovascular and renal diseases. The onset of obesity is linked to an increase of senescent cells within adipose tissue and other organs. Cellular senescence is a stress response that has been shown to be causally linked to aging and development of various age-related diseases such as obesity. The senescence-associated-secretory phenotype of senescent cells creates a chronic inflammatory milieu that leads to local and systemic dysfunction. The elimination of senescent cells using pharmacological approaches (i.e., senolytics) has been shown to delay, prevent, or alleviate obesity-related organ dysfunction.
Sarcopenic obesity in rheumatoid arthritis: prevalence and impact on physical functioning.
Rheumatology (Oxford, England)
OBJECTIVE:We determined the prevalence of sarcopenic obesity in patients with RA using multiple methods and assessed associations with physical functioning. METHODS:This study evaluated data from three RA cohorts. Whole-body dual-energy absorptiometry (DXA) measures of appendicular lean mass index (ALMI, kg/m2) and fat mass index (FMI) were converted to age, sex and race-specific Z-Scores and categorized using a recently validated method and compared it to a widely-used existing method. The prevalence of body composition abnormalities in RA was compared with two reference populations. In the RA cohorts, associations between body composition and change in the HAQ and the Short Physical Performance Battery (SPPB) in follow-up were assessed using linear and logistic regression, adjusting for age, sex, race and study. RESULTS:The prevalence of low lean mass and sarcopenic obesity was higher in patients with RA (14.2; 12.6%, respectively) compared with the reference population cohorts (7-10%; 4-4.5%, respectively, all P <0.05). There was only moderate agreement among methods of sarcopenic obesity categorization (Kappa 0.45). The recently validated method categorized fewer subjects as obese, and many of these were categorized as low lean mass only. Low lean mass, obesity and sarcopenic obesity were each associated with higher HAQ and lower SPPB at baseline and numerically greater worsening. CONCLUSION:RA patients had higher rates of low lean mass and sarcopenic obesity than the general population. The recently validated methods characterized body composition changes differently from traditional methods and were more strongly associated with physical function.
Obesity and endocrine therapy resistance in breast cancer: Mechanistic insights and perspectives.
Obesity reviews : an official journal of the International Association for the Study of Obesity
The incidence of obesity, a recognized risk factor for various metabolic and chronic diseases, including numerous types of cancers, has risen dramatically over the recent decades worldwide. To date, convincing research in this area has painted a complex picture about the adverse impact of high body adiposity on breast cancer onset and progression. However, an emerging but overlooked issue of clinical significance is the limited efficacy of the conventional endocrine therapies with selective estrogen receptor modulators (SERMs) or degraders (SERDs) and aromatase inhibitors (AIs) in patients affected by breast cancer and obesity. The mechanisms behind the interplay between obesity and endocrine therapy resistance are likely to be multifactorial. Therefore, what have we actually learned during these years and which are the main challenges in the field? In this review, we will critically discuss the epidemiological evidence linking obesity to endocrine therapeutic responses and we will outline the molecular players involved in this harmful connection. Given the escalating global epidemic of obesity, advances in understanding this critical node will offer new precision medicine-based therapeutic interventions and more appropriate dosing schedule for treating patients affected by obesity and with breast tumors resistant to endocrine therapies.
Obesity and reproduction: a committee opinion.
Fertility and sterility
The purpose of this American Society for Reproductive Medicine Practice Committee report is to provide clinicians with principles and strategies for the evaluation and treatment of couples with infertility associated with obesity. This revised document replaces the Practice Committee document titled "Obesity and reproduction: an educational bulletin" last published in 2015 (Fertil Steril 2015;104:1116-26).
Causal Association Between Serum Thyrotropin and Obesity: A Bidirectional, Mendelian Randomization Study.
Wang Xichang,Gao Xiaotong,Han Yutong,Zhang Fan,Lin Zheyu,Wang Hong,Teng Weiping,Shan Zhongyan
The Journal of clinical endocrinology and metabolism
CONTEXT:The association between serum thyrotropin (TSH) and obesity traits has been investigated previously in several epidemiological studies. However, the underlying causal association has not been established. OBJECTIVE:This work aimed to determine and analyze the causal association between serum TSH level and obesity-related traits (body mass index [BMI] and obesity). METHODS:The latest genome-wide association studies (GWASs) on TSH, BMI, and obesity were searched to obtain full statistics. Bidirectional 2-sample mendelian randomization (MR) was performed to explore the causal relationship between serum TSH and BMI and obesity. The inverse variance-weighted (IVW) and MR-Egger methods were used to combine the estimation for each single-nucleotide variation (formerly single-nucleotide polymorphism). Based on the preliminary MR results, free thyroxine (fT4) and free 3,5,3'-triiodothyronine (fT3) levels were also set as outcomes to further analyze the impact of BMI on them. BMI and obesity were treated as the outcomes to evaluate the effect of serum TSH on them, and TSH was set as the outcome to estimate the effect of BMI and obesity on it. RESULTS:IVW and MR-Egger results both indicated that genetically driven serum TSH did not causally lead to changes in BMI or obesity. Moreover, the IVW method showed that the TSH level could be significantly elevated by genetically predicted high BMI (β = .038, SE = 0.013, P = .004). In further MR analysis, the IVW method indicated that BMI could causally increase the fT3 (β = 10.123, SE = 2.523, P < .001) while not significantly affecting the fT4 level. CONCLUSION:Together with fT3, TSH can be significantly elevated by an increase in genetically driven BMI.
Implication of Heterozygous Variants in Genes of the Leptin-Melanocortin Pathway in Severe Obesity.
Courbage Sophie,Poitou Christine,Le Beyec-Le Bihan Johanne,Karsenty Alexandra,Lemale Julie,Pelloux Véronique,Lacorte Jean-Marc,Carel Jean-Claude,Lecomte Nathalie,Storey Caroline,De Filippo Gianpaolo,Coupaye Muriel,Oppert Jean-Michel,Tounian Patrick,Clément Karine,Dubern Béatrice
The Journal of clinical endocrinology and metabolism
CONTEXT:Unlike homozygous variants, the implication of heterozygous variants on the leptin-melanocortin pathway in severe obesity has not been established. OBJECTIVE:To describe the frequency, the phenotype, and the genotype-phenotype relationship for heterozygous variants in LEP, LEPR, POMC, and PCSK1 in severe obesity. METHODS:In this retrospective study, genotyping was performed on at least 1 of the LEP, LEPR, POMC, and PCSK1 genes in 1486 probands with severe obesity (600 children, 886 adults). The phenotype was collected in 60 subjects with heterozygous variants and 16 with homozygous variants. We analyzed variant frequency, body mass index (BMI), age of obesity onset, food impulsivity, and endocrine abnormalities. RESULTS:The frequency of subjects with homozygous variants was 1.7% (n = 26), and 6.7% (n = 100) with heterozygous variants. Adults with homozygous variants had a higher BMI (66 vs 53 kg/m2, P = .015), an earlier onset of obesity (0.4 vs 5.4 years, P < .001), more often food impulsivity (83% vs 42%, P = .04), and endocrine abnormalities (75% vs 26%, P < .01). The BMI was higher for subjects with high-impact heterozygous variants (61 vs 50 kg/m², P = .045) and those with a second heterozygous variant on the pathway (65 vs 49 kg/m², P < .01). In children, no significant differences were found for the age of obesity onset and BMI. CONCLUSION:Heterozygous variants in LEP, LEPR, POMC, and PCSK1 are frequent in severe obesity and sometimes associated with a phenotype close to that of homozygotes. These data suggest a systematic search for variants in severe early-onset obesity, to discuss therapy that targets this key pathway.
Obesity and long-term outcomes after incident stroke: a prospective population-based cohort study.
Akyea Ralph K,Doehner Wolfram,Iyen Barbara,Weng Stephen F,Qureshi Nadeem,Ntaios George
Journal of cachexia, sarcopenia and muscle
BACKGROUND:The association between obesity, major adverse cardiovascular events (MACE), and mortality in patients with incident stroke is not well established. We assessed the relationship between body mass index (BMI) and MACE in patients with incident stroke. METHODS:The population-based cohort study identified 30 702 individuals from the Clinical Practice Research Datalink (CPRD GOLD) and Hospital Episode Statistics (HES) databases from the United Kingdom. Individuals were aged ≥18 years with incident stroke between 1-1-1998 and 31-12-2017, a BMI recorded within 24 months before incident stroke, and no prior history of MACE. BMI was categorized as underweight (<18.5 kg/m ), normal (18.5-24.9 kg/m ), overweight (25.0-29.9 kg/m ), obesity class I (30.0-34.9 kg/m ), class II (35.0-39.9 kg/m ) and class III (≥40 kg/m2). MACE was defined as a composite of incident coronary heart disease, recurrent stroke, peripheral vascular disease (PVD), heart failure, and cardiovascular-related mortality. Multivariable Cox regression was used to assess differences in MACE risk between BMI categories. RESULTS:At baseline, 1217 (4.0%) were underweight, 10 783 (35.1%) had a normal BMI, 10 979 (35.8%) had overweight, 5206 (17.0%) had obesity Class I, 1749 (5.7%) Class II, and 768 (2.5%) Class III. In multivariable analysis, higher BMI were associated with lower risk of subsequent MACE [overweight: HR 0.96, 95% CI 0.93-0.99)]; PVD [overweight: 0.65 (0.49-0.85); obesity Class III: 0.19 (0.50-0.77)]; cardiovascular-related death [overweight: 0.80 (0.74-0.86); obesity Class I: 0.79 (0.71-0.88); Class II: 0.80 (0.67-0.96)]; and all-cause mortality [overweight: 0.75 (0.71-0.79); obesity Class I: 0.75 (0.70-0.81); Class II: 0.77 (0.68-0.86)] when compared to those with normal BMI. The results were similar irrespective of sex, diabetes mellitus, smoking or cancer at time of incident stroke. CONCLUSIONS:In patients with incident stroke, overweight or obesity were associated with a more favourable prognosis for subsequent MACE, PVD, and mortality, irrespective of sex, diabetes mellitus, smoking, or cancer at baseline. As with other cohort studies, our study demonstrates an association. Randomized control trials should be considered to robustly evaluate the impact of weight management recommendations on subsequent cardiovascular outcomes in stroke survivors.
Adipose expression of CREB3L3 modulates body weight during obesity.
McCann Maximilian A,Li Yanliang,Muñoz Marcos,Gil Victoria,Qiang Guifen,Cordoba-Chacon Jose,Blüher Matthias,Duncan Stephen,Liew Chong Wee
We found the hepatic transcription factor Cyclic-AMP Responsive Element Binding Protein 3-like-3 (CREB3L3) to be expressed in adipose tissue, and selectively downregulated in the more metabolically protective subcutaneous adipose tissue in obese mice and humans. We sought to elucidate the specific role of this factor in adipose biology. CREB3L3 fat-specific knockout mice were fed a high-fat diet to induce obesity and metabolic dysfunction. Additionally, we injected a flip-excision adeno-associated virus directly into the subcutaneous inguinal adipose tissue of Adiponectin-Cre mice to create a depot-specific overexpression model for further assessment. Fat-specific ablation of CREB3L3 enhanced weight gain and insulin resistance following high-fat feeding, as fat-specific knockout mice expended less energy and possessed more inflammatory adipose tissue. Conversely, inguinal fat CREB3L3 overexpression deterred diet-induced obesity and ameliorated metabolic dysfunction. Together, this study highlights the relevance of CREB3L3 in obese adipose tissue and demonstrates its role as a powerful body weight modulator.
Abdominal obesity and metabolic syndrome in South Asians: prevention and management.
Jayawardena Ranil,Sooriyaarachchi Piumika,Misra Anoop
Expert review of endocrinology & metabolism
INTRODUCTION:The prevalence of metabolic syndrome (MetS) and abdominal obesity are in South countries. It is well established that MetS is associated with increased risk for both Type 2 diabetes mellitus and cardiovascular diseases. South Asians have an increased risk of MetS due to a variety of factors including unhealthy lifestyle and their unique body composition. AREAS COVERED:In this review, we discuss the prevalence, associated risk factors, and evidence-based preventive and curative strategies for MetS and abdominal obesity in South Asians. A literature search through PubMed®, Web of Science®, and Scopus® was performed for studies published before 31 April 2021. A combination of the following keywords was used with the names of the individual South Asian countries: 'metabolic syndrome,' 'syndrome X,' 'abdominal obesity,' 'central obesity,' 'visceral obesity,' 'prevention,' and 'management.' EXPERT OPINION:According to current evidence, MetS and abdominal obesity are highly prevalent among South Asians. Several risk factors, such as lifestyle, socio-demography, cultural, and body composition, are associated with MetS. Limited research shows culturally tailored lifestyle interventions are effective in preventing and managing MetS and abdominal obesity among South Asians.
The Critical Role of Oxidative Stress in Sarcopenic Obesity.
Gonzalez Andrea,Simon Felipe,Achiardi Oscar,Vilos Cristian,Cabrera Daniel,Cabello-Verrugio Claudio
Oxidative medicine and cellular longevity
Sarcopenic obesity (SO) is a combination of obesity and sarcopenia that primarily develops in older people. Patients with SO have high fat mass, low muscle mass, low muscle strength, and low physical function. SO relates to metabolic syndrome and an increased risk of morbimortality. The prevalence of SO varies because of lacking consensus criteria regarding its definition and the methodological difficulty in diagnosing sarcopenia and obesity. SO includes systemic alterations such as insulin resistance, increased proinflammatory cytokines, age-associated hormonal changes, and decreased physical activity at pathophysiological levels. Interestingly, these alterations are influenced by oxidative stress, which is a critical factor in altering muscle function and the generation of metabolic dysfunctions. Thus, oxidative stress in SO alters muscle mass, the signaling pathways that control it, satellite cell functions, and mitochondrial and endoplasmic reticulum activities. Considering this background, our objectives in this review are to describe SO as a highly prevalent condition and look at the role of oxidative stress in SO pathophysiology.
PPAR-gamma agonists: Potential modulators of autophagy in obesity.
Faghfouri Amir Hossein,Khajebishak Yaser,Payahoo Laleh,Faghfuri Elnaz,Alivand Mohammadreza
European journal of pharmacology
Autophagy pathways are involved in the pathogenesis of some obesity related health problems. As obesity is a nutrient sufficiency condition, autophagy process can be altered in obesity through AMP activated protein kinase (AMPK) inhibition. Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) as the main modulator of adipogenesis process can be effective in the regulation of obesity related phenotypes. As well, it has been revealed that PPAR-gamma and its agonists can regulate autophagy in different normal or cancer cells. However, their effects on autophagy modulation in obesity have been investigated in the limited number of studies. In the current comprehensive mechanistic review, we aimed to investigate the possible mechanisms of action of PPAR-gamma on the process of autophagy in obesity through narrating the effects of PPAR-gamma on autophagy in the non-obesity conditions. Moreover, mode of action of PPAR-gamma agonists on autophagy related implications comprehensively reviewed in the various studies. Understanding the different effects of PPAR-gamma agonists on autophagy in obesity can help to develop a new approach to management of obesity.
Epigenetic regulation of energy metabolism in obesity.
Gao Wei,Liu Jia-Li,Lu Xiang,Yang Qin
Journal of molecular cell biology
Obesity has reached epidemic proportions globally. Although modern adoption of a sedentary lifestyle coupled with energy-dense nutrition is considered to be the main cause of obesity epidemic, genetic preposition contributes significantly to the imbalanced energy metabolism in obesity. However, the variants of genetic loci identified from large-scale genetic studies do not appear to fully explain the rapid increase in obesity epidemic in the last four to five decades. Recent advancements of next-generation sequencing technologies and studies of tissue-specific effects of epigenetic factors in metabolic organs have significantly advanced our understanding of epigenetic regulation of energy metabolism in obesity. The epigenome, including DNA methylation, histone modifications, and RNA-mediated processes, is characterized as mitotically or meiotically heritable changes in gene function without alteration of DNA sequence. Importantly, epigenetic modifications are reversible. Therefore, comprehensively understanding the landscape of epigenetic regulation of energy metabolism could unravel novel molecular targets for obesity treatment. In this review, we summarize the current knowledge on the roles of DNA methylation, histone modifications such as methylation and acetylation, and RNA-mediated processes in regulating energy metabolism. We also discuss the effects of lifestyle modifications and therapeutic agents on epigenetic regulation of energy metabolism in obesity.
Evidence-based obesity prevention in childhood and adolescence: critique of recent etiological studies, preventive interventions, and policies.
Advances in nutrition (Bethesda, Md.)
Prevention of obesity in childhood and adolescence remains a worthwhile and realistic goal, but preventive efforts have been beset by a number of problems, which are the subject of this review. The review draws on recent systematic reviews and evidence appraisals and has a United Kingdom (UK) perspective because there is a rich evidence base in the United Kingdom that may be helpful to obesity prevention researchers elsewhere. Recent evidence of a leveling off in child and adolescent obesity prevalence in some Western nations should not encourage the belief that the obesity prevention problem has been solved, although a better understanding of recent secular trends might be helpful for prevention strategy in future. An adequate body of evidence provides behavioral targets of preventive interventions, and there are frameworks for prioritizing these targets logically and models for translating them into generalizable interventions with a wide reach (e.g., school-based prevention interventions such as Planet Health). An improved understanding of the "energy gap" that children and adolescents experience would be helpful to the design of preventive interventions and to their tailoring to particular groups. In the United Kingdom, some recent etiological evidence has been taken as indicative of the need for paradigm shifts in obesity prevention, but this evidence from single studies has not been replicated, and paradigm shifts probably occur only rarely. Ensuring that the evidence base on etiology and prevention influences policy effectively remains one of the greatest challenges for childhood obesity researchers.
Health benefits of fruits and vegetables.
Advances in nutrition (Bethesda, Md.)
Fruits and vegetables are universally promoted as healthy. The Dietary Guidelines for Americans 2010 recommend you make one-half of your plate fruits and vegetables. Myplate.gov also supports that one-half the plate should be fruits and vegetables. Fruits and vegetables include a diverse group of plant foods that vary greatly in content of energy and nutrients. Additionally, fruits and vegetables supply dietary fiber, and fiber intake is linked to lower incidence of cardiovascular disease and obesity. Fruits and vegetables also supply vitamins and minerals to the diet and are sources of phytochemicals that function as antioxidants, phytoestrogens, and antiinflammatory agents and through other protective mechanisms. In this review, we describe the existing dietary guidance on intake of fruits and vegetables. We also review attempts to characterize fruits and vegetables into groups based on similar chemical structures and functions. Differences among fruits and vegetables in nutrient composition are detailed. We summarize the epidemiological and clinical studies on the health benefits of fruits and vegetables. Finally, we discuss the role of fiber in fruits and vegetables in disease prevention.
Beige adipocytes are a distinct type of thermogenic fat cell in mouse and human.
Wu Jun,Boström Pontus,Sparks Lauren M,Ye Li,Choi Jang Hyun,Giang An-Hoa,Khandekar Melin,Virtanen Kirsi A,Nuutila Pirjo,Schaart Gert,Huang Kexin,Tu Hua,van Marken Lichtenbelt Wouter D,Hoeks Joris,Enerbäck Sven,Schrauwen Patrick,Spiegelman Bruce M
Brown fat generates heat via the mitochondrial uncoupling protein UCP1, defending against hypothermia and obesity. Recent data suggest that there are two distinct types of brown fat: classical brown fat derived from a myf-5 cellular lineage and UCP1-positive cells that emerge in white fat from a non-myf-5 lineage. Here, we report the isolation of "beige" cells from murine white fat depots. Beige cells resemble white fat cells in having extremely low basal expression of UCP1, but, like classical brown fat, they respond to cyclic AMP stimulation with high UCP1 expression and respiration rates. Beige cells have a gene expression pattern distinct from either white or brown fat and are preferentially sensitive to the polypeptide hormone irisin. Finally, we provide evidence that previously identified brown fat deposits in adult humans are composed of beige adipocytes. These data provide a foundation for studying this mammalian cell type with therapeutic potential. PAPERCLIP:
Metabolically unhealthy individuals, either with obesity or not, have a higher risk of critical coronavirus disease 2019 outcomes than metabolically healthy individuals without obesity.
Kim Nam Hoon,Kim Kyeong Jin,Choi Jimi,Kim Sin Gon
Metabolism: clinical and experimental
BACKGROUND:This study aimed to determine the relative and independent contributions of impaired metabolic health and obesity to critical coronavirus disease 2019 (COVID-19). METHODS:We analyzed 4069 COVID-19 patients between January and June 2020 in South Korea, classified into four groups according to metabolic health status and body mass index (BMI): metabolically healthy normal weight (MHNW), metabolically unhealthy normal weight (MUNW), metabolically healthy obesity (MHO), and metabolically unhealthy obesity (MUO). The primary outcome was a composite of intensive care unit (ICU) admission, invasive mechanical ventilation (IMV), extracorporeal membrane oxygenation (ECMO), and death. Multivariable Cox proportional hazard regression models were used to estimate the hazard ratio (HR) for the outcome. RESULTS:The incidence rate (per 100 person-months) of critical COVID-19 was the lowest in the MHNW group (0.90), followed by the MHO (1.64), MUNW (3.37), and MUO (3.37) groups. Compared with MHNW, a significantly increased risk of critical COVID-19 was observed in MUNW (HR, 1.41; 95% CI, 1.01-1.98) and MUO (HR, 1.77; 95% CI, 1.39-2.44) but not in MHO (HR, 1.48; 95% CI, 0.98-2.23). The risk of ICU admission or IMV/ECMO was increased only in MUO; however, the risk of death was significantly higher in MUNW and MUO. The risk of critical COVID-19 increased insignificantly by 2% per 1 kg/m BMI increase but significantly by 13% per 1 metabolically unhealthy component increase, even after mutually adjusting for BMI and metabolic health status. CONCLUSIONS:Metabolic health is more important to COVID-19 outcomes than obesity itself, suggesting that metabolic health status should be considered for a precise and tailored management of COVID-19 patients.
Obesity in people living with type 1 diabetes.
Van der Schueren Bart,Ellis Darcy,Faradji Raquel N,Al-Ozairi Eeba,Rosen Jonathan,Mathieu Chantal
The lancet. Diabetes & endocrinology
Although type 1 diabetes is traditionally considered a disease of lean people, overweight and obesity are becoming increasingly more common in individuals with type 1 diabetes. Non-physiological insulin replacement that causes peripheral hyperinsulinaemia, insulin profiles that do not match basal and mealtime insulin needs, defensive snacking to avoid hypoglycaemia, or a combination of these, are believed to affect body composition and drive excessive accumulation of body fat in people with type 1 diabetes. The consequences of overweight or obesity in people with type 1 diabetes are of particular concern, as they increase the risk of both diabetes-related and obesity-related complications, including cardiovascular disease, stroke, and various types of cancer. In this Review, we summarise the current understanding of the aetiology and consequences of excessive bodyweight in people with type 1 diabetes and highlight the need to optimise future prevention and treatment strategies in this population.
Sexual Orientation and Obesity: What Do We Know?
Current obesity reports
PURPOSE OF REVIEW:This review describes research addressing sexual orientation disparities in obesity and their sequelae, with a focus on new findings from the past year and areas for future work. RECENT FINDINGS:Sexual minority people of color experience important health disparities related to obesity. Sexual minority women may be at greater risk of developing type 2 diabetes than their heterosexual counterparts, potentially because of obesity-related disparities. Bisexual men also appear to experience more obesity and potential greater risk for type 2 diabetes than heterosexual men. Stigma and discrimination are important emerging areas for additional research to better understand sexual orientation disparities in obesity-related health. There is a need for intersectional research and longitudinal research that connects existing sexual orientation disparities in obesity with subsequent chronic disease development. Additionally, upstream efforts to understand the impact of stigma and discrimination on the weight-related health of sexual minority groups are needed.
Ketogenic diet as an advanced option for the management of pediatric obesity.
Current opinion in endocrinology, diabetes, and obesity
PURPOSE OF REVIEW:The Duke Healthy Lifestyles Program (HL), established in 2006, has treated over 15,000 pediatric patients with obesity. A subset of patients with obesity do not respond to dietary and lifestyle changes. Development of the Staged Transitional Eating Plan (STEP) in 2012 provided a ketogenic advanced dietary option for these specific patients. RECENT FINDINGS:The goal of STEP is to facilitate weight loss, while assuring adequacy and the promotion of health through the abundant inclusion of vegetables, fatty fish, nuts, olive oil, and other foods consistent with the Mediterranean Diet. STEP is a three-phase eating plan, each with a defined carbohydrate limit. STEP is ideal for patients eager to try a low carbohydrate diet, those with good vegetable acceptance, and those with families who are able to participate in the same eating plan as them. SUMMARY:STEP, the HL version of low carbohydrate high fat eating, is a safe dietary intervention for a carefully selected subset of pediatric patients with obesity who are trying to lose weight.
Hepatic miR-144 Drives Fumarase Activity Preventing NRF2 Activation During Obesity.
BACKGROUND AND AIMS:Oxidative stress plays a key role in the development of metabolic complications associated with obesity, including insulin resistance and the most common chronic liver disease worldwide, nonalcoholic fatty liver disease. We have recently discovered that the microRNA miR-144 regulates protein levels of the master mediator of the antioxidant response, nuclear factor erythroid 2-related factor 2 (NRF2). On miR-144 silencing, the expression of NRF2 target genes was significantly upregulated, suggesting that miR-144 controls NRF2 at the level of both protein expression and activity. Here we explored a mechanism whereby hepatic miR-144 inhibited NRF2 activity upon obesity via the regulation of the tricarboxylic acid (TCA) metabolite, fumarate, a potent activator of NRF2. METHODS:We performed transcriptomic analysis in liver macrophages (LMs) of obese mice and identified the immuno-responsive gene 1 (Irg1) as a target of miR-144. IRG1 catalyzes the production of a TCA derivative, itaconate, an inhibitor of succinate dehydrogenase (SDH). TCA enzyme activities and kinetics were analyzed after miR-144 silencing in obese mice and human liver organoids using single-cell activity assays in situ and molecular dynamic simulations. RESULTS:Increased levels of miR-144 in obesity were associated with reduced expression of Irg1, which was restored on miR-144 silencing in vitro and in vivo. Furthermore, miR-144 overexpression reduces Irg1 expression and the production of itaconate in vitro. In alignment with the reduction in IRG1 levels and itaconate production, we observed an upregulation of SDH activity during obesity. Surprisingly, however, fumarate hydratase (FH) activity was also upregulated in obese livers, leading to the depletion of its substrate fumarate. miR-144 silencing selectively reduced the activities of both SDH and FH resulting in the accumulation of their related substrates succinate and fumarate. Moreover, molecular dynamics analyses revealed the potential role of itaconate as a competitive inhibitor of not only SDH but also FH. Combined, these results demonstrate that silencing of miR-144 inhibits the activity of NRF2 through decreased fumarate production in obesity. CONCLUSIONS:Herein we unravel a novel mechanism whereby miR-144 inhibits NRF2 activity through the consumption of fumarate by activation of FH. Our study demonstrates that hepatic miR-144 triggers a hyperactive FH in the TCA cycle leading to an impaired antioxidant response in obesity.
Hyperinsulinemia in Obesity, Inflammation, and Cancer.
Diabetes & metabolism journal
The relative insufficiency of insulin secretion and/or insulin action causes diabetes. However, obesity and type 2 diabetes mellitus can be associated with an absolute increase in circulating insulin, a state known as hyperinsulinemia. Studies are beginning to elucidate the cause-effect relationships between hyperinsulinemia and numerous consequences of metabolic dysfunctions. Here, we review recent evidence demonstrating that hyperinsulinemia may play a role in inflammation, aging and development of cancers. In this review, we will focus on the consequences and mechanisms of excess insulin production and action, placing recent findings that have challenged dogma in the context of the existing body of literature. Where relevant, we elaborate on the role of specific signal transduction components in the actions of insulin and consequences of chronic hyperinsulinemia. By discussing the involvement of hyperinsulinemia in various metabolic and other chronic diseases, we may identify more effective therapeutics or lifestyle interventions for preventing or treating obesity, diabetes and cancer. We also seek to identify pertinent questions that are ripe for future investigation.
Gender Differences in Obesity-Related Cancers.
Argyrakopoulou Georgia,Dalamaga Maria,Spyrou Nikolaos,Kokkinos Alexander
Current obesity reports
PURPOSE OF REVIEW:In this review, we summarize the role of obesity in carcinogenesis, providing details on specific cancer sites. Special emphasis is given to gender differences in obesity-related cancers and on the effect of bariatric surgery on cancer risk. RECENT FINDINGS:Accumulating evidence has highlighted the detrimental role of overweight/obesity in cancer, with almost 55% of cancers diagnosed in women and 24% diagnosed in men considered overweight- and obesity-related cancers. Sufficient data have shown that higher BMI is associated with risk of gynecologic malignancies (mainly breast and endometrial cancers) as well as cancers in sites such as the esophagus (adenocarcinoma), gastric cardia, colon, rectum, liver, gallbladder, pancreas, kidney, thyroid gland, and multiple myeloma. The main mechanisms underlying this relationship include the insulin/IGF1 system, the effect of sex hormones, and adipocytokines. Marked differences may be seen in specific cancer sites when comparing men to women. There is a higher overall incidence of obesity-related cancers among females (endometrial, ovarian, and postmenopausal female breast cancers), whereas cancers that concern both sexes show a higher incidence in males, particularly esophageal adenocarcinoma (male to female ratio: 9: 1 in the USA). Additionally, bariatric surgery has provided evidence of lowering overall cancer risk in patients with morbid obesity. Interestingly, bariatric surgery may lower overall cancer risk in women within the first 5 years after surgery due to the reduced risk of breast and endometrial cancer, and non-Hodgkin lymphoma. Obesity constitutes the base for marked metabolic, hormonal, and inflammatory alterations, including increased cancer risk in both men and women. Implementation of early obesity prevention strategies could ameliorate the continuously increasing incidence of cancer attributed to obesity.
Vitamin D and Obesity: Current Evidence and Controversies.
Karampela Irene,Sakelliou Alexandra,Vallianou Natalia,Christodoulatos Gerasimos-Socrates,Magkos Faidon,Dalamaga Maria
Current obesity reports
PURPOSE OF REVIEW:Evidence from observational studies suggests that obesity is associated with low vitamin D. As both obesity and hypovitaminosis D present an alarmingly increased prevalence worldwide, there is an intense research interest to clarify all aspects of this association. This review summarizes current evidence from meta-analyses investigating vitamin D status in obesity, including the effects of weight loss and bariatric surgery on vitamin D status and the outcomes of vitamin D supplementation on body weight. We also discuss potential pathophysiologic mechanisms and important controversies. RECENT FINDINGS:Data from meta-analyses consistently support an inverse association of vitamin D levels with body weight. However, the impact of weight loss on improving vitamin D status is small, while studies on the supplementation with vitamin D after bariatric surgery have shown conflicting results regarding vitamin D status. Moreover, interventional studies do not support a beneficial effect of vitamin D supplementation on body weight. These findings warrant a cautious interpretation due to important methodological limitations and confounding factors, such as high heterogeneity of studies, variable methods of determination of vitamin D and definition of deficiency/insufficiency, use of various adiposity measures and definitions of obesity, and inadequate adjustment for confounding variables influencing vitamin D levels. The underlying pathogenetic mechanisms associating low vitamin D in obesity include volumetric dilution, sequestration into adipose tissue, limited sunlight exposure, and decreased vitamin D synthesis in the adipose tissue and liver. Experimental studies have demonstrated that low vitamin D may be implicated in adipose tissue differentiation and growth leading to obesity either by regulation of gene expression or through modulation of parathyroid hormone, calcium, and leptin. Obesity is associated with low vitamin D status but weight loss has little effect on improving this; vitamin D supplementation is also not associated with weight loss. Evidence regarding vitamin D status after bariatric surgery is contradicting. The link between vitamin D and obesity remains controversial due to important limitations and confounding of studies. More research is needed to clarify the complex interplay between vitamin D and adiposity.
Maternal obesity increases the risk and severity of NAFLD in offspring.
Hagström Hannes,Simon Tracey G,Roelstraete Bjorn,Stephansson Olof,Söderling Jonas,Ludvigsson Jonas F
Journal of hepatology
BACKGROUND & AIMS:Maternal obesity has been linked to the development of cardiovascular disease and diabetes in offspring, but its relationship to non-alcoholic fatty liver disease (NAFLD) is unclear. METHODS:Through the nationwide ESPRESSO cohort study we identified all individuals ≤25 years of age in Sweden with biopsy-verified NAFLD diagnosed between 1992 and 2016 (n = 165). These were matched by age, sex, and calendar year with up to 5 controls (n = 717). Through linkage with the nationwide Swedish Medical Birth Register (MBR) we retrieved data on maternal early-pregnancy BMI, and possible confounders, in order to calculate adjusted odds ratios (aORs) for NAFLD in offspring. RESULTS:Maternal BMI was associated with NAFLD in offspring: underweight (aOR 0.84; 95% CI 0.14-5.15), normal weight (reference, aOR 1), overweight (aOR 1.51; 0.95-2.40), and obese (aOR 3.26; 1.72-6.19) women. Severe NAFLD (biopsy-proven fibrosis or cirrhosis) was also more common in offspring of overweight (aOR 1.94; 95% CI 0.96-3.90) and obese (aOR 3.67; 95% CI 1.61-8.38) mothers. Associations were similar after adjusting for maternal pre-eclampsia and gestational diabetes. Socio-economic parameters (smoking, mother born outside the Nordic countries and less than 10 years of basic education) were also associated with NAFLD in offspring but did not materially alter the effect size of maternal BMI in a multivariable model. CONCLUSIONS:This nationwide study found a strong association between maternal overweight/obesity and future NAFLD in offspring. Adjusting for socio-economic and metabolic parameters in the mother did not affect this finding, suggesting that maternal obesity is an independent risk factor for NAFLD in offspring. LAY SUMMARY:In a study of all young persons in Sweden with a liver biopsy consistent with fatty liver, the authors found that compared to matched controls, the risk of fatty liver was much higher in those with obese mothers. This was independent of available confounders and suggests that the high prevalence of obesity in younger persons might lead to a higher risk of fatty liver in their offspring.
Dynapenic abdominal obesity in hospitalized elderly patients with acute myocardial infarction.
da Silva Clécia Alves,Mendes Roberta Maria Lins,de Moraes Santana Natália,Dos Santos Natalia Fernandes,Pinho Cláudia Porto Sabino
Obesity and dynapenia are cardiovascular risk factors. When present together, it is called dynapenic abdominal obesity and can potentiate adverse outcomes. This study aims to estimate the prevalence of dynapenic abdominal obesity and its relationship with prognostic markers in patients with acute myocardial infarction (AMI). This is a hybrid study with a longitudinal component plus a cross-sectional component at baseline involving elderly patients admitted to a reference hospital in cardiology due to AMI in the Brazilian Northeast from May to October 2015. We analyzed patients' admission data and evaluated some prognostic markers up to two years after admission. We established abdominal obesity by measuring waist circumference (>102 cm for men and >88 cm for women) and dynapenia by handgrip strength (<27 kg/F for men and <16 kg/F for women). We considered the prognostic markers troponin and creatinine kinase - MB (CKMB), AMI classification according to ST segment elevation, TIMI score, need for coronary angioplasty or coronary artery bypass surgery, complications during hospitalization and within two years after admission, and re-admission to the same service. We evaluated 92 patients with a mean age of 71.4 ± 7.5 years. The prevalence of abdominal obesity and dynapenia was 56.5% and 44.6%, respectively. The coexistence of the two conditions occurred in 25.0% of the patients, being higher among women (p < 0.001). When comparing the dynapenic abdominal obese groups with the group of patients who had one of the two isolated conditions we observed that, for a same mean age and clinical characteristics, patients with only one of the conditions had a higher CKMB (p = 0.046) and troponin median (p = 0.032). The presence of dynapenia in the groups of abdominal obese and non-abdominal obese individuals is not associated with risk marker parameters (p > 0.05). High prevalence of abdominal obesity and dynapenia occurred among patients with AMI and in a quarter of these both conditions coexisted. Dynapenic abdominal obesitydoes not increase the risk of adverse outcomes and isolated dynapenia is not a marker of a poor prognosis.
Subtyping youngsters with obesity: A theory-based cluster analysis.
Vervoort L,Naets T,Goossens L,Verbeken S,Claes L,Tanghe A,Braet C
Psychological mechanisms play a crucial role in explaining weight gain. Aim of the present study was to identify subtypes in youngsters with obesity in line with these mechanisms. Defining homogeneous clusters within this heterogeneous group provides relevant information for personalized treatments. Data were collected in N = 572 participants (51% boys, aged 7-19) with extreme obesity (%BMI M = 187.8; SD = 30.9) recruited in an inpatient treatment centre. Based on psychological models of overweight/obesity, the Affect Regulation Model, the Reward Deficiency Model and The Dual Pathway Model, cluster variables were selected assessing emotional eating, reward reactivity and regulative capacities. Youngsters reported on emotional eating (DEBQ Emotional Eating) and reward sensitivity (BAS), while parents reported on children's regulative Executive Functions (BRIEF). Characteristics of the different clusters were examined concerning weight variables (pre and post treatment) and variables indexing problematic eating (DEBQ External Eating, Ch-EDE), affect regulation (FEEL-KJ) and depressive symptoms (CDI). Hierarchical cluster analyses supported the presence of three clusters, further evaluated by K-means cluster analyses. The cluster solutions differed according to age and sex (boys 7-13, boys 14-19, girls 7-13, girls 14-19). In all four age and gender subsamples, an "Emotional Eating" cluster displaying a vulnerable profile (high depression, maladaptive emotion regulation, problematic eating) and a "Reward Deficiency" cluster displaying a more resilient profile were detected. In girls 7-13, a "Weak Executive Functioning" indicative of insufficient self-regulative capacities, showed moderate to high emotional problems and problematic eating. In the other subgroups, the "Mean Level Functioning" cluster also showed elevated emotional problems and problematic eating. Given that different clusters can be identified, and given that these clusters have different profiles on emotional problems and problematic eating, subtyping youngsters with severe obesity is indicated, setting the stage for personalized treatments.
Metabolically healthy obesity and cardiovascular events: A nationwide cohort study.
Fauchier Grégoire,Bisson Arnaud,Bodin Alexandre,Herbert Julien,Semaan Carl,Angoulvant Denis,Ducluzeau Pierre Henri,Lip Gregory Y H,Fauchier Laurent
Diabetes, obesity & metabolism
AIM:To evaluate the associations between metabolically healthy obesity (MHO) and different types of incident cardiovascular events in a contemporary population. MATERIALS AND METHODS:All patients discharged from French hospitals in 2013 with at least 5 years of follow-up and without a history of major adverse cardiovascular event (MACE; myocardial infarction, heart failure [HF], ischaemic stroke or cardiovascular death [MACE-HF]) or underweight/malnutrition were identified. They were categorized by phenotypes defined by obesity and three metabolic abnormalities (diabetes, hypertension and hyperlipidaemia). Hazard ratios (HRs) for cardiovascular events during follow-up were adjusted on age, sex and smoking status at baseline. RESULTS:In total, 2 873 039 individuals were included in the analysis, among whom 272 838 (9.5%) had obesity. During a mean follow-up of 4.9 years, when pooling men and women, individuals with MHO had a higher risk of MACE-HF (multivariate-adjusted HR 1.22, 95% confidence interval [CI]: 1.19-1.24), new-onset HF (HR 1.34, 95% CI 1.31-1.37) and atrial fibrillation (AF; HR 1.33, 95% CI 1.30-1.37) compared with individuals with no obesity and zero metabolic abnormalities. By contrast, risks were not higher for myocardial infarction (HR 0.92, 95% CI 0.87-0.98), ischaemic stroke (HR 0.93, 95% CI 0.88-0.98) and cardiovascular death (HR 0.99, 95% CI 0.93-1.04). MHO in men was associated with a higher risk of clinical events compared with metabolically healthy men of normal weight (HR 1.12-1.80), while women with MHO had a lower risk for most events than metabolically healthy women of normal weight (HR 0.49-0.99). CONCLUSIONS:In a large and contemporary analysis of patients seen in French hospitals, individuals with MHO did not have a higher risk of myocardial infarction, ischaemic stroke or cardiovascular death than metabolically healthy individuals with no obesity. By contrast, they had a higher risk of new-onset HF and new-onset AF. However, notable differences were observed in men and women in the sex-stratified analysis.
Obesity and sleep disturbances: The "chicken or the egg" question.
Rodrigues Gabriel Dias,Fiorelli Elisa M,Furlan Ludovico,Montano Nicola,Tobaldini Eleonora
European journal of internal medicine
Obesity and sleep disturbances are common conditions in modern societies and accumulating evidence support a close bidirectional causal relationship between these two conditions. Indeed, from one side sleep loss seems to affect energy intake and expenditure through its direct effects on hormone-mediated sensations of satiety and hunger and through the influence on hedonic and psychological aspects of food consumption. Sleep deprived patients have been shown to experiment excessive daytime sleepiness, fatigue, and tiredness that, in a vicious circle, enhances physical inactivity and weight gain. On the other side, obesity is a well-known risk factor for several sleep disorders. This narrative review will discuss the main pathophysiological mechanisms that link sleep loss to obesity and metabolic syndrome with particular attention to the three most common sleep disorders (insomnia, obstructive sleep apnoea syndrome, restless leg syndrome).
Sex hormones regulate metainflammation in diet-induced obesity in mice.
Varghese Mita,Griffin Cameron,Abrishami Simin,Eter Leila,Lanzetta Nicholas,Hak Layla,Clemente Jeremy,Agarwal Devyani,Lerner Arianna,Westerhoff Maria,Patel Ravi,Bowers Emily,Islam Mohammed,Subbaiah Perla,Singer Kanakadurga
The Journal of biological chemistry
Men have a statistically higher risk of metabolic and cardiovascular disease than premenopausal women, but the mechanisms mediating these differences are elusive. Chronic inflammation during obesity contributes to disease risk and is significantly more robust in males. Prior work demonstrated that compared with obese males, obese females have reduced proinflammatory adipose tissue macrophages (ATMs). Given the paucity of data on how sex hormones contribute to macrophage responses in obesity, we sought to understand the role of sex hormones in promoting obesity-induced myeloid inflammation. We used gonadectomy, estrogen receptor-deficient alpha chimeras, and androgen-insensitive mice to model sex hormone deficiency. These models were evaluated in diet-induced obesity conditions (high-fat diet [HFD]) and in vitro myeloid assays. We found that ovariectomy increased weight gain and adiposity. Ovariectomized females had increased ATMs and bone marrow myeloid colonies compared with sham-gonadectomized females. In addition, castrated males exposed to HFD had improved glucose tolerance, insulin sensitivity, and adiposity with fewer Ly6c monocytes and bone marrow myeloid colonies compared with sham-gonadectomized males, although local adipose inflammation was enhanced. Similar findings were observed in androgen-insensitive mice; however, these mice had fewer CD11c ATMs, implying a developmental role for androgens in myelopoiesis and adipose inflammation. We concluded that gonadectomy results in convergence of metabolic and inflammatory responses to HFD between the sexes, and that myeloid estrogen receptor alpha contributes minimally to diet-induced inflammatory responses, whereas loss of androgen-receptor signaling improves metabolic and inflammatory outcomes. These studies demonstrate that sex hormones play a critical role in sex differences in obesity, metabolic dysfunction, and myeloid inflammation.
Sweet taste and obesity.
Ribeiro Gabriela,Oliveira-Maia Albino J
European journal of internal medicine
For more than 50 years, there has been evidence for greater consumption of sweet- foods in overweight humans and animals, relative to those that have a normal weight. Furthermore, it has long been suggested that energy deficit resulting from dieting, while moving the individual from a higher weight set point, would result in heightened susceptibility to palatable tastants, namely to sweet tastants. This was the motivation behind the first studies comparing sweet taste perception between individuals with obesity and those of a normal weight. These studies, using direct measures of taste, have been characterized by significant methodological heterogeneity, contributing towards variability in results and conclusions. Nevertheless, some of these findings have been used to support the theory that patients with obesity have decreased taste perception, particularly for sweet tastants. A similar hypothesis has been proposed regarding evidence for reduced brain dopamine receptors in obesity and, in both cases, it is proposed that increased food consumption, and associated weight gain, result from the need to increase sensory and brain stimulation. However, the available literature is not conclusive on the association between obesity and reduced sweet taste perception, with both negative and contradictory findings in comparisons between individuals with obesity and normal weight control subjects, as well as within-subject comparisons before and after bariatric surgery. Nevertheless, following either Roux-en-Y gastric bypass or sleeve gastrectomy, there is evidence of changes in taste perception, particularly for reward-related measures of sweet tastants, that should be further tested and confirmed in large samples, using consensual methodology.
Polysaccharides from mulberry (Morus alba L.) leaf prevents obesity by inhibiting pancreatic lipase in high-fat diet induced mice.
Li Ruilin,Xue Zihan,Jia Yanan,Wang Yajie,Li Shuqin,Zhou Jingna,Liu Junyu,Zhang Min,He Chengwei,Chen Haixia
International journal of biological macromolecules
Pancreatic lipase (PL) is a key enzyme related to the prevention and treatment of obesity. The aim of the study was to evaluate the inhibitory effects of mulberry leaf polysaccharides (MLP) on PL and possible interaction mechanism, inhibition on lipid accumulation in vitro and in vivo. The results revealed that MLP had obvious inhibitory effects on PL (P < 0.05). The interaction of MLP-PL complexes was in a spontaneous way driven by enthalpy, and hydrogen bonds were the main factors in the binding. MLP could significantly inhibit the development of lipid accumulation in HepG2 cells (P < 0.05). Furthermore, consumption of high-fat diet containing MLP showed protective effects on liver and adipose tissue damages in mice, and inhibited the lipid absorption in digestive tract. MLP also significantly reduced the increased expression level of pancreatic digestive enzymes (P < 0.05). The study indicated that the anti-obesity effect of MLP might be caused by inhibition of lipid absorption via reducing PL activity.
Transcriptional characterization of subcutaneous adipose tissue in obesity affected women highlights metabolic dysfunction and implications for lncRNAs.
Rey Federica,Messa Letizia,Pandini Cecilia,Barzaghini Bianca,Micheletto Giancarlo,Raimondi Manuela Teresa,Bertoli Simona,Cereda Cristina,Zuccotti Gian Vincenzo,Cancello Raffaella,Carelli Stephana
Obesity is a complex disease with multifactorial causes, and its prevalence is becoming a serious health crisis. For this reason, there is a crucial need to identify novel targets and players. With this aim in mind, we analyzed via RNA-sequencing the subcutaneous adipose tissue of normal weight and obesity-affected women, highlighting the differential expression in the two tissues. We specifically focused on long non-coding RNAs, as 6 of these emerged as dysregulated in the diseased-tissue (COL4A2-AS2, RPS21-AS, PELATON, ITGB2-AS1, ACER2-AS and CTEPHA1). For each of them, we performed both a thorough in silico dissection and in vitro validation, to predict their function during adipogenesis. We report the lncRNAs expression during adipose derived stem cells differentiation to adipocytes as model of adipogenesis and their potential modulation by adipogenesis-related transcription factors (C/EBPs and PPARγ). Moreover, inhibiting CTEPHA1 expression we investigated its impact on adipogenesis-related transcription factors, showing its significative dysregulation of C/EBPα expression. Lastly, we dissected the subcellular localization, pathway involvement and disease-correlation for coding differentially expressed genes. Together, these findings highlight a transcriptional deregulation at the basis of obesity, impacted by both coding and long non-coding RNAs.
GPNMB plays a protective role against obesity-related metabolic disorders by reducing macrophage inflammatory capacity.
Prabata Adam,Ikeda Koji,Rahardini Elda Putri,Hirata Ken-Ichi,Emoto Noriaki
The Journal of biological chemistry
Obesity is a global health problem that is often related to cardiovascular and metabolic diseases. Chronic low-grade inflammation in white adipose tissue (WAT) is a hallmark of obesity. Previously, during a search for differentially expressed genes in WAT of obese mice, we identified glycoprotein nonmetastatic melanoma protein B (GPNMB), of which expression was robustly induced in pathologically expanded WAT. Here, we investigated the role of GPNMB in obesity-related metabolic disorders utilizing GPNMB-deficient mice. When fed a high-fat diet (HFD), GPNMB-deficient mice showed body weight and adiposity similar to those of wild-type (WT) mice. Nonetheless, insulin and glucose tolerance tests revealed significant obesity-related metabolic disorders in GPNMB-KO mice compared with WT mice fed with HFD. Chronic WAT inflammation was remarkably worsened in HFD-fed GPNMB-KO mice, accompanied by a striking increase in crown-like structures, typical hallmarks for diseased WAT. Macrophages isolated from GPNMB-KO mice were observed to produce more inflammatory cytokines than those of WT mice, a difference abolished by supplementation with recombinant soluble GPNMB extracellular domain. We demonstrated that GPNMB reduced the inflammatory capacity of macrophages by inhibiting NF-κB signaling largely through binding to CD44. Finally, we showed that macrophage depletion by addition of clodronate liposomes abolished the worsened WAT inflammation and abrogated the exacerbation of metabolic disorders in GPNMB-deficient mice fed on HFD. Our data reveal that GPNMB negatively regulates macrophage inflammatory capacities and ameliorates the WAT inflammation in obesity; therefore we conclude that GPNMB is a promising therapeutic target for the treatment of metabolic disorders associated with obesity.
Using multiple Mendelian randomization approaches and genetic correlations to understand obesity, urate, and gout.
Adams Charleen D,Boutwell Brian B
Observational studies suggest relationships between obesity, urate, and gout but are possibly confounded. We assessed whether genetically determined obesity, higher urate (and related traits), and gout were causal using multiple Mendelian randomization (MR) approaches and linkage disequilibrium score regression for genetic correlations (r). For data, we used genome-wide association study summary statistics available through MR-Base. We observed that obesity increased urate (beta = 0.127; 95% CI = 0.098, 0.157; P-value = 1.2E-17; r = 0.25 [P-value = 0.001]) and triglycerides (beta = 0.082; 95% CI = 0.065, 0.099; P-value = 1.2E-21; r = 0.23 [P-value = 8.8E-12]) and decreased high-density lipoprotein cholesterol (HDL) (beta = - 0.083; 95% CI = - 0.101, - 0.065; P-value = 2.5E-19; r = - 0.28; [P-value = 5.2E-24]). Higher triglycerides increased urate (beta = 0.198; 95% CI = 0.146, 0.251; P-value = 8.9E-14; r = 0.29 [P-value = 0.001]) and higher HDL decreased urate (beta = - 0.109; 95% CI = - 0.148, - 0.071; P-value = 2.7E- 08; r = - 0.21 [P-value = 9.8E-05]). Higher urate (OR = 1.030; 95% CI = 1.028, 1.032; P-value = 1.1E-130; r = 0.89 [P-value = 1.7E-55]) and obesity caused gout (OR = 1.003; 95% CI = 1.001, 1.004; P-value = 1.3E-04; r = 0.23 [P-value = 2.7E-05]). Obesity on gout with urate as a mediator revealed all the effect of obesity on gout occurred through urate. Obesity on low-density lipoprotein cholesterol (LDL) was null (beta = -0.011; 95% CI = -0.030, 0.008; P-value = 2.6E-01; r = 0.03 [P-value = 0.369]). A multivariable MR of obesity, HDL, and triglycerides on urate showed obesity influenced urate when accounting for HDL and triglycerides. Obesity's impact on urate was exacerbated by it decreasing HDL.
A systematic review of economic evaluations of web-based or telephone-delivered interventions for preventing overweight and obesity and/or improving obesity-related behaviors.
Brown Vicki,Tran Huong,Downing Katherine L,Hesketh Kylie D,Moodie Marj
Obesity reviews : an official journal of the International Association for the Study of Obesity
Obesity prevention interventions with behavioral or lifestyle-related components delivered via web-based or telephone technologies have been reported as comparatively low cost as compared with other intervention delivery modes, yet to date, no synthesized evidence of cost-effectiveness has been published. This study aimed to conduct a systematic review of economic evaluations of obesity prevention interventions with a telehealth or eHealth intervention component. A systematic search of six academic databases was conducted through October 2020. Studies were included if they reported full economic evaluations of interventions aimed at preventing overweight or obesity, or interventions aimed at improving obesity-related behaviors, with at least one intervention component delivered by telephone (telehealth) or web-based technology (eHealth). Findings were reported narratively, based on the Consolidated Health Economic Evaluation Reporting Standards. Twenty-seven economic evaluations were included from 20 studies meeting the inclusion criteria. Sixteen of the included interventions had a telehealth component, whereas 11 had an eHealth component. Seventeen interventions were evaluated using cost-utility analysis, five with cost-effectiveness analysis, and five undertook both cost-effectiveness and cost-utility analyses. Only eight cost-utility analyses reported that the intervention was cost-effective. Comparison of results from cost-effectiveness analyses was limited by heterogeneity in methods and outcome units reported. The evidence supporting the cost-effectiveness of interventions with a telehealth or eHealth delivery component is currently inconclusive. Although obesity prevention telehealth and eHealth interventions are gaining popularity, more evidence is required on their effectiveness and cost-effectiveness.
Obesity and responsibility: Is it time to rethink agency?
Grannell Andrew,Fallon Finian,Al-Najim Werd,le Roux Carel
Obesity reviews : an official journal of the International Association for the Study of Obesity
Despite obesity declared a disease, there still exists considerable weight stigma in both popular culture and health care, which negatively impacts policy making regarding prevention and treatment. While viewed as a choice or a failure of willpower by many, evidence exists to challenge the argument that both weight gain and failure to achieve weight loss maintenance are the individuals' fault due to personal failure or lack of responsibility. In this article, we draw upon literature from obesity treatment, neuroscience, philosophy of mind, and weight stigma to challenge the commonly held beliefs that individuals are free to choose how much they can weigh, and achievement of long-term weight loss maintenance is completely subject to conscious choice. In reality, the regulation of hunger, satiety, energy balance, and body weight takes place in subcortical regions of the brain. Thus, hunger and satiety signals are generated in regions of the brain, which are not associated with conscious experience. This points towards biological determinism of weight and challenges ideas of willpower and resultant moralization regarding body weight regulation. In this article, we will thus argue that in the context of dysregulation of hunger and satiety contributing to the obesity epidemic, a wider discourse related to personal responsibility and the stigma of obesity is needed to enhance understanding, prevention, and treatment of this complex disease. Obesity is a chronic disease requiring personalized treatment. Lifestyle interventions alone may not be enough to achieve medically significant and sustained weight loss for many individuals with obesity. By understanding that obesity is not due to a lack of motivation or willpower, the availability and utilization of additional treatments or combination of treatments such as lifestyle, pharmacotherapy, and surgery are likely to improve the quality of life for many suffering with this disease.
Physical exercise consequences on memory in obesity: A systematic review.
De Sousa Ricardo Augusto Leoni,Santos Letícia Gomes,Lopes Paulo Maurício,Cavalcante Bruno Raphael Ribeiro,Improta-Caria Alex Cleber,Cassilhas Ricardo Cardoso
Obesity reviews : an official journal of the International Association for the Study of Obesity
Obesity is associated with changes in memory. Thus, the aim of this systematic review was to investigate the physical exercise consequences on memory in obesity. A search was carried out in the PubMed, Lilacs, and Scielo databases with the following descriptors: "physical exercise," "memory," and "obesity." A total of 16 studies were analyzed in this review. Low, moderate, and high intensity exercise training showed positive effects on memory in patients with obesity (100%). The animal models of obesity used in their physical exercise protocols: treadmill (72.7%) or wheel running (27.3%). Most of the animal studies (81.8%) revealed positive effects of the physical exercise protocol on memory in obesity. Mouse was the most commonly used animal (54.5%), and a 60% high-fat diet (HFD) was the most commonly method used to induce obesity (82%). We did not identify any knockout model of obesity that was used to evaluate memory and used physical exercise as the main intervention. Thus, exercise training, independently if it is resistance or endurance training, seems to be an excellent intervention to prevent and inhibit cognitive impairment and memory loss on obese patients and animal models of obesity.
Patient initiation and maintenance of GLP-1 RAs for treatment of obesity.
Patel Dhiren,Smith April
Expert review of clinical pharmacology
Healthcare providers (HCPs) see many patients with obesity-related complications and are therefore well placed to help treat obesity itself. However, limited collated information exists to help HCPs with the practical use of anti-obesity medications (AOMs). We focus on the initiation and maintenance of a glucagon-like peptide-1 receptor agonist (GLP-1 RA) for weight management, liraglutide 3.0 mg. Literature search was conducted between 25-28 November 2019 on PubMed and ClinicalTrials.gov. Clinical trial and real-world data describing weight-loss efficacy, cardiometabolic risk factors, incidence of adverse events (AEs), and persistence are presented to assist HCPs with patient discussions. Practical considerations to overcome barriers to optimal use are provided, equipping HCPs with the information required to aid with adherence to and persistence with AOMs. The use of other GLP-1- RA therapies in obesity is discussed in light of the recent US Food and Drug Administration approval of semaglutide 2.4 mg for weight management. Liraglutide 3.0 mg provides benefits regarding weight loss and improvements in cardiometabolic risk factors. Promising areas of future research in the field of obesity include dual receptor agonists and the combination of glucagon-like peptide-1 receptor agonists with other molecules.
LMO3 reprograms visceral adipocyte metabolism during obesity.
Wagner Gabriel,Fenzl Anna,Lindroos-Christensen Josefine,Einwallner Elisa,Husa Julia,Witzeneder Nadine,Rauscher Sabine,Gröger Marion,Derdak Sophia,Mohr Thomas,Sutterlüty Hedwig,Klinglmüller Florian,Wolkerstorfer Silviya,Fondi Martina,Hoermann Gregor,Cao Lei,Wagner Oswald,Kiefer Florian W,Esterbauer Harald,Bilban Martin
Journal of molecular medicine (Berlin, Germany)
Obesity and body fat distribution are important risk factors for the development of type 2 diabetes and metabolic syndrome. Evidence has accumulated that this risk is related to intrinsic differences in behavior of adipocytes in different fat depots. We recently identified LIM domain only 3 (LMO3) in human mature visceral adipocytes; however, its function in these cells is currently unknown. The aim of this study was to determine the potential involvement of LMO3-dependent pathways in the modulation of key functions of mature adipocytes during obesity. Based on a recently engineered hybrid rAAV serotype Rec2 shown to efficiently transduce both brown adipose tissue (BAT) and white adipose tissue (WAT), we delivered YFP or Lmo3 to epididymal WAT (eWAT) of C57Bl6/J mice on a high-fat diet (HFD). The effects of eWAT transduction on metabolic parameters were evaluated 10 weeks later. To further define the role of LMO3 in insulin-stimulated glucose uptake, insulin signaling, adipocyte bioenergetics, as well as endocrine function, experiments were conducted in 3T3-L1 adipocytes and newly differentiated human primary mature adipocytes, engineered for transient gain or loss of LMO3 expression, respectively. AAV transduction of eWAT results in strong and stable Lmo3 expression specifically in the adipocyte fraction over a course of 10 weeks with HFD feeding. LMO3 expression in eWAT significantly improved insulin sensitivity and healthy visceral adipose tissue expansion in diet-induced obesity, paralleled by increased serum adiponectin. In vitro, LMO3 expression in 3T3-L1 adipocytes increased PPARγ transcriptional activity, insulin-stimulated GLUT4 translocation and glucose uptake, as well as mitochondrial oxidative capacity in addition to fatty acid oxidation. Mechanistically, LMO3 induced the PPARγ coregulator Ncoa1, which was required for LMO3 to enhance glucose uptake and mitochondrial oxidative gene expression. In human mature adipocytes, LMO3 overexpression promoted, while silencing of LMO3 suppressed mitochondrial oxidative capacity. LMO3 expression in visceral adipose tissue regulates multiple genes that preserve adipose tissue functionality during obesity, such as glucose metabolism, insulin sensitivity, mitochondrial function, and adiponectin secretion. Together with increased PPARγ activity and Ncoa1 expression, these gene expression changes promote insulin-induced GLUT4 translocation, glucose uptake in addition to increased mitochondrial oxidative capacity, limiting HFD-induced adipose dysfunction. These data add LMO3 as a novel regulator improving visceral adipose tissue function during obesity. KEY MESSAGES: LMO3 increases beneficial visceral adipose tissue expansion and insulin sensitivity in vivo. LMO3 increases glucose uptake and oxidative mitochondrial activity in adipocytes. LMO3 increases nuclear coactivator 1 (Ncoa1). LMO3-enhanced glucose uptake and mitochondrial gene expression requires Ncoa1.
Children with Severe Obesity in Family-Based Obesity Treatment Compared with Other Participants: Conclusions Depend on Metrics.
Hayes Jacqueline F,Fowler Lauren A,Balantekin Katherine N,Saelens Brian E,Stein Richard I,Perri Michael G,Welch R Robinson,Epstein Leonard H,Wilfley Denise E
Obesity (Silver Spring, Md.)
OBJECTIVE:This study compares children with severe obesity and children with mild obesity/overweight participating in family-based obesity treatment (FBT) on change in (1) relative weight and adiposity and (2) psychosocial distress. METHODS:Children 7 to 11 years old (N = 241) and their parents participated in 12 months of behavioral treatment (FBT + maintenance treatment) and completed anthropometric, adiposity, and psychosocial assessments (psychiatric disorder symptomology, quality of life). Severe obesity was defined as a baseline BMI ≥ 120% of the 95th percentile (N = 105). RESULTS:At 12 months, 40% of children with baseline severe obesity no longer had severe obesity. Percent overweight and fat mass index measurements showed similar magnitudes of change among children with severe obesity and children with mild obesity/overweight, whereas BMI z score and percent body fat change was lower in the group with severe obesity. Youth with severe obesity were higher on some measures of psychosocial distress at baseline but generally experienced improvements similar to children with mild obesity/overweight. CONCLUSIONS:FBT with maintenance treatment is beneficial for children with severe obesity and is recommended for use prior to more invasive treatments in severe pediatric obesity. Future studies should assess the necessity of additional treatment, as children with severe obesity still have high relative weights post intervention.
The Impact of Obesity on Critical Illnesses.
Shock (Augusta, Ga.)
ABSTRACT:In the last few decades, obesity became one of the world's greatest health challenges reaching a size of global epidemic in virtually all socioeconomic statuses and all age groups. Obesity is a risk factor for many health problems and as its prevalence gradually increases is becoming a significant economic and health burden. In this manuscript we describe how normal respiratory and cardiovascular physiology is altered by obesity. We review past and current literature to describe how obesity affects outcomes of patients facing critical illnesses and discuss some controversies related to this topic.
Weight stigma and obesity-related policies: A systematic review of the state of the literature.
Obesity reviews : an official journal of the International Association for the Study of Obesity
Weight stigma is an important issue colliding with obesity-related policies; both have population health and social impacts. Our aim was to conduct a systematic review of the peer-reviewed literature that combined the concepts of stigma, obesity, and policy. We searched PsycINFO, Medline, Scopus, and Google Scholar for peer-reviewed articles amalgamating terms relevant to stigma, obesity, and policy. Of 3219 records identified, 47 were included in the narrative synthesis. Two key types of studies emerged: studies investigating factors associated with support for obesity-related policies and those exploring policy implementation and evaluation. We found that support for nonstigmatizing obesity-related policies was higher when obesity was attributed as an environmental rather than individual problem. An undercurrent theme suggested that views that blame individuals for their obesity were associated with support for punitive policies for people living in larger bodies. Real-world policies often implicitly condoned stigma through poor language choice and conflicting discourse. Our findings inform recommendations for policy makers that broader socioecological stigma-reduction approaches are needed to fully address the issue of weight stigma in obesity-related policies. Efforts are needed in the research and policy sectors to understand how to improve the design and support of nonstigmatizing obesity-related policies.
Macrophage IRX3 promotes diet-induced obesity and metabolic inflammation.
Yao Jingfei,Wu Dongmei,Zhang Chunyan,Yan Ting,Zhao Yiheng,Shen Hongyu,Xue Kaili,Huang Xun,Wang Zihao,Qiu Yifu
Metabolic inflammation is closely linked to obesity, and is implicated in the pathogenesis of metabolic diseases. FTO harbors the strongest genetic association with polygenic obesity, and IRX3 mediates the effects of FTO on body weight. However, in what cells and how IRX3 carries out this control are poorly understood. Here we report that macrophage IRX3 promotes metabolic inflammation to accelerate the development of obesity and type 2 diabetes. Mice with myeloid-specific deletion of Irx3 were protected against diet-induced obesity and metabolic diseases via increasing adaptive thermogenesis. Mechanistically, macrophage IRX3 promoted proinflammatory cytokine transcription and thus repressed adipocyte adrenergic signaling, thereby inhibiting lipolysis and thermogenesis. JNK1/2 phosphorylated IRX3, leading to its dimerization and nuclear translocation for transcription. Further, lipopolysaccharide stimulation stabilized IRX3 by inhibiting its ubiquitination, which amplified the transcriptional capacity of IRX3. Together, our findings identify a new player, macrophage IRX3, in the control of body weight and metabolic inflammation, implicating IRX3 as a therapeutic target.
Endocrine-disrupting chemicals and obesity risk: A review of recommendations for obesity prevention policies.
Lobstein Tim,Brownell Kelly D
Obesity reviews : an official journal of the International Association for the Study of Obesity
Emerging evidence indicates that industrially produced endocrine-disrupting chemicals (EDCs) may be as obesogenic as poor dietary patterns and should be considered in obesity prevention policies. The authors conducted two reviews: (a) a systematic search of four electronic databases for papers published since January 2010 to identify the policy recommendations contained in scientific reviews of EDC exposure and obesity risk and (b) a narrative review of obesity policy documents published since January 2012 to identify the recommendations of national and international agencies. A search of four electronic databases found 63 scientific reviews with policy recommendations, of which 26 suggested individual responsibility to avoid exposure, 11 suggested medical interventions to counter the effects of exposure, and 42 suggested regulatory control of hazardous chemicals. Of sixty policy documents examined, six mentioned pollutants as a possible risk factor for obesity, and only one made explicit reference to strategies for reducing exposure to EDCs. The UN Sustainable Development Goals include targets to prevent ill health from hazardous chemicals (Targets 3.9 and 12.4) and to remove unsafe industrial chemicals from the environment (Targets 6.3, 11.6, 12.4, and 14.1). The authors suggest these should be explicitly linked to World Health Assembly targets to halt the rise in obesity.
Synergizing Mouse and Human Studies to Understand the Heterogeneity of Obesity.
Advances in nutrition (Bethesda, Md.)
Obesity is routinely considered as a single disease state, which drives a "one-size-fits-all" approach to treatment. We recently convened the first annual University of North Carolina Interdisciplinary Nutrition Sciences Symposium to discuss the heterogeneity of obesity and the need for translational science to advance understanding of this heterogeneity. The symposium aimed to advance scientific rigor in translational studies from animal to human models with the goal of identifying underlying mechanisms and treatments. In this review, we discuss fundamental gaps in knowledge of the heterogeneity of obesity ranging from cellular to population perspectives. We also advocate approaches to overcoming limitations in the field. Examples include the use of contemporary mouse genetic reference population models such as the Collaborative Cross and Diversity Outbred mice that effectively model human genetic diversity and the use of translational models that integrate -omics and computational approaches from pre-clinical to clinical models of obesity. Finally, we suggest best scientific practices to ensure strong rigor that will allow investigators to delineate the sources of heterogeneity in the population with obesity. Collectively, we propose that it is critical to think of obesity as a heterogeneous disease with complex mechanisms and etiologies, requiring unique prevention and treatment strategies tailored to the individual.
Genetics of Sleep and Insights into Its Relationship with Obesity.
Dashti Hassan S,Ordovás José M
Annual review of nutrition
Considerable recent advancements in elucidating the genetic architecture of sleep traits and sleep disorders may provide insight into the relationship between sleep and obesity. Despite the involvement of the circadian clock in sleep and metabolism, few shared genes, including , were implicated in genome-wide association studies (GWASs) of sleep and obesity. Polygenic scores composed of signals from GWASs of sleep traits show largely null associations with obesity, suggesting lead variants are unique to sleep. Modest genome-wide genetic correlations are observed between many sleep traits and obesity and are largest for snoring. Notably, U-shaped positive genetic correlations with body mass index (BMI) exist for both short and long sleep durations. Findings from Mendelian randomization suggest robust causal effects of insomnia on higher BMI and, conversely, of higher BMI on snoring and daytime sleepiness. In addition, bidirectional effects between sleep duration and daytime napping with obesity may also exist. Limited gene-sleep interaction studies suggest that achieving favorable sleep, as part of a healthy lifestyle, may attenuate genetic predisposition to obesity,but whether these improvements produce clinically meaningful reductions in obesity risk remains unclear. Investigations of the genetic link between sleep and obesity for sleep disorders other than insomnia and in populations of non-European ancestry are currently limited.
A systematic literature review on obesity: Understanding the causes & consequences of obesity and reviewing various machine learning approaches used to predict obesity.
Safaei Mahmood,Sundararajan Elankovan A,Driss Maha,Boulila Wadii,Shapi'i Azrulhizam
Computers in biology and medicine
Obesity is considered a principal public health concern and ranked as the fifth foremost reason for death globally. Overweight and obesity are one of the main lifestyle illnesses that leads to further health concerns and contributes to numerous chronic diseases, including cancers, diabetes, metabolic syndrome, and cardiovascular diseases. The World Health Organization also predicted that 30% of death in the world will be initiated with lifestyle diseases in 2030 and can be stopped through the suitable identification and addressing of associated risk factors and behavioral involvement policies. Thus, detecting and diagnosing obesity as early as possible is crucial. Therefore, the machine learning approach is a promising solution to early predictions of obesity and the risk of overweight because it can offer quick, immediate, and accurate identification of risk factors and condition likelihoods. The present study conducted a systematic literature review to examine obesity research and machine learning techniques for the prevention and treatment of obesity from 2010 to 2020. Accordingly, 93 papers are identified from the review articles as primary studies from an initial pool of over 700 papers addressing obesity. Consequently, this study initially recognized the significant potential factors that influence and cause adult obesity. Next, the main diseases and health consequences of obesity and overweight are investigated. Ultimately, this study recognized the machine learning methods that can be used for the prediction of obesity. Finally, this study seeks to support decision-makers looking to understand the impact of obesity on health in the general population and identify outcomes that can be used to guide health authorities and public health to further mitigate threats and effectively guide obese people globally.
GLP-1 physiology informs the pharmacotherapy of obesity.
Drucker Daniel J
BACKGROUND:Glucagon-like peptide-1 receptor agonists (GLP1RA) augment glucose-dependent insulin release and reduce glucagon secretion and gastric emptying, enabling their successful development for the treatment of type 2 diabetes (T2D). These agents also inhibit food intake and reduce body weight, fostering investigation of GLP1RA for the treatment of obesity. SCOPE OF REVIEW:Here I discuss the physiology of Glucagon-like peptide-1 (GLP-1) action in the control of food intake in animals and humans, highlighting the importance of gut vs. brain-derived GLP-1 for the control of feeding and body weight. The widespread distribution and function of multiple GLP-1 receptor (GLP1R) populations in the central and autonomic nervous system are outlined, and the importance of pathways controlling energy expenditure in preclinical studies vs. reduction of food intake in both animals and humans is highlighted. The relative contributions of vagal afferent pathways vs. GLP1R+ populations in the central nervous system for the physiological reduction of food intake and the anorectic response to GLP1RA are compared and reviewed. Key data enabling the development of two GLP1RA for obesity therapy (liraglutide 3 mg daily and semaglutide 2.4 mg once weekly) are discussed. Finally, emerging data potentially supporting the combination of GLP-1 with additional peptide epitopes in unimolecular multi-agonists, as well as in fixed-dose combination therapies, are highlighted. MAJOR CONCLUSIONS:The actions of GLP-1 to reduce food intake and body weight are highly conserved in obese animals and humans, in both adolescents and adults. The well-defined mechanisms of GLP-1 action through a single G protein-coupled receptor, together with the extensive safety database of GLP1RA in people with T2D, provide reassurance surrounding the long-term use of these agents in people with obesity and multiple co-morbidities. GLP1RA may also be effective in conditions associated with obesity, such as cardiovascular disease and non-alcoholic steatohepatitis (NASH). Progressive improvements in the efficacy of GLP1RA suggest that GLP-1-based therapies may soon rival bariatric surgery as viable options for the treatment of obesity and its complications.
Nutrition and cellular senescence in obesity-related disorders.
Rubio-Tomás Teresa,Rueda-Robles Ascensión,Plaza-Díaz Julio,Álvarez-Mercado Ana I
The Journal of nutritional biochemistry
Adequate nutrition is vital for immune homeostasis. However, the incidence of obesity is increasing worldwide due to the adoption of the Western diet and a sedentary lifestyle. Obesity is associated with chronic inflammation which alters the function of adipose tissue, liver, pancreas, and the nervous system. Inflammation is related to cellular senescence, distinguished by irreversible cell cycle arrest. Senescent cells secrete the senescence-associated secretory phenotype (SASP) which contains pro-inflammatory factors. Targeting processes in senescence might have a salutary approach to obesity. The present review highlights the impact of an unhealthy diet on tissues affected by obesity, and the mechanisms that promote the consequent inflammation and senescence.
Vascular reactivity contributes to adipose tissue remodeling in obesity.
Lee Hye-Jin,Shi Haifei,Brönneke Hella S,Jin Bo-Yeong,Choi Sang-Hyun,Seeley Randy J,Kim Dong-Hoon
The Journal of endocrinology
Vascular reactivity of adipose tissue (AT) is hypothesized to play an important role in the development of obesity. However, the exact role of vascular reactivity in the development of obesity remains unclear. In this study, we investigated the chronological changes in vascular reactivity and the microenvironments of the visceral AT (VAT) and subcutaneous AT (SAT) in lean and obese mice. Changes in blood flow levels induced by a β-adrenoceptor agonist (isoproterenol) were significantly lower in the VAT of the mice fed a high-fat diet (HFD) for 1 and 12 weeks than those in the VAT of the mice fed a low-fat diet (LFD) for the same period; no significant change was observed in the SAT of any mouse group, suggesting depot-specific vascular reactivity of AT. Moreover, the hypoxic area and the expression of genes associated with angiogenesis and macrophage recruitment were increased in the VAT (but not in the SAT) of mice fed an HFD for 1 week compared with mice fed an LFD. These changes occurred with no morphological changes, including those related to adipocyte size, AT vessel density, and the diameter and pericyte coverage of the endothelium, suggesting a determinant role of vascular reactivity in the type of AT remodeling. The suppression of vascular reactivity was accompanied by increased endothelin1 (Edn1) gene expression and extracellular matrix (ECM) stiffness only in the VAT, implying enhanced contractile activities of the vasculature and ECM. The results suggest a depot-specific role of vascular reactivity in AT remodeling during the development of obesity.
Sex/Gender Differences in Obesity Prevalence, Comorbidities, and Treatment.
Cooper Ashley J,Gupta Sapana R,Moustafa Afaf F,Chao Ariana M
Current obesity reports
PURPOSE OF REVIEW:Obesity is a heterogeneous condition, yet sex/gender is rarely considered in the prevention or clinical care of this disease. This review examined and evaluated recent literature regarding the influence of sex and gender on obesity prevalence, comorbidities, and treatment in adults. RECENT FINDINGS:Obesity is more prevalent in women than men in most countries, but in some countries and population subgroups, this gap is more pronounced. Several obesity-related comorbidities, including type 2 diabetes and hypertension, demonstrate sex-specific pathways. Women, compared to men, are more likely to be diagnosed with obesity and seek and obtain all types of obesity treatment including behavioral, pharmacological, and bariatric surgery. Men tend to have greater absolute weight loss, but this difference is attenuated once accounting for baseline weight. Obesity is a multifactorial condition with complex interactions among sex/gender, sociocultural, environmental, and physiological factors. More sex/gender research is needed to investigate mechanisms underlying sex/gender differences in prevalence, comorbidities, and treatment, identify ways to increase men's interest and participation in obesity treatment, and examine differences in obesity prevalence and treatments for transgender and gender non-conforming individuals.
Obesity and hyperinsulinemia drive adipocytes to activate a cell cycle program and senesce.
Obesity is considered an important factor for many chronic diseases, including diabetes, cardiovascular disease and cancer. The expansion of adipose tissue in obesity is due to an increase in both adipocyte progenitor differentiation and mature adipocyte cell size. Adipocytes, however, are thought to be unable to divide or enter the cell cycle. We demonstrate that mature human adipocytes unexpectedly display a gene and protein signature indicative of an active cell cycle program. Adipocyte cell cycle progression associates with obesity and hyperinsulinemia, with a concomitant increase in cell size, nuclear size and nuclear DNA content. Chronic hyperinsulinemia in vitro or in humans, however, is associated with subsequent cell cycle exit, leading to a premature senescent transcriptomic and secretory profile in adipocytes. Premature senescence is rapidly becoming recognized as an important mediator of stress-induced tissue dysfunction. By demonstrating that adipocytes can activate a cell cycle program, we define a mechanism whereby mature human adipocytes senesce. We further show that by targeting the adipocyte cell cycle program using metformin, it is possible to influence adipocyte senescence and obesity-associated adipose tissue inflammation.
The Role of GIP Receptor in the CNS for the Pathogenesis of Obesity.
Glucose-dependent insulinotropic polypeptide (GIP) (also known as gastric inhibitory polypeptide) is a hormone produced in the upper gut and secreted to the circulation in response to the ingestion of foods, especially fatty foods. Growing evidence supports the physiological and pharmacological relevance of GIP in obesity. In an obesity setting, inhibition of endogenous GIP or its receptor leads to decreased energy intake, increased energy expenditure, or both, eventually causing weight loss. Further, supraphysiological dosing of exogenous long-lasting GIP agonists alters energy balance and has a marked antiobesity effect. This remarkable yet paradoxical antiobesity effect is suggested to occur primarily via the brain. The brain is capable of regulating both energy intake and expenditure and plays a critical role in human obesity. In addition, the GIP receptor is widely distributed throughout the brain, including areas responsible for energy homeostasis. Recent studies have uncovered previously underappreciated roles of the GIP receptor in the brain in the context of obesity. This article highlights how the GIP receptor expressed by the brain impacts obesity-related pathogenesis.
Help or hindrance: The obesity paradox in cancer treatment response.
O'Connell Fiona,O'Sullivan Jacintha
Obesity is a rising epidemic, the influence of which on cancer development, progression as well as its impact on current standard of care cancer treatments is profound with many facets. Obesity is emerging as a modulating factor in many cancer therapies, such as chemotherapy, radiotherapy, immunotherapy and combination therapies. It has been reported to diminish the efficacy of some treatments but has also been alluded to being protective in terms of reduced treatment toxicities, thus the evolution of the obesity paradox. The obese tumour microenvironment influences treatment response through modulation of a series of aspects, including altered adipocyte secretome, angiogenesis, hypoxia, fibrosis, free fatty acid uptake as well as a modulated immune landscape. However, the influence of these underlying mechanisms on cancer treatment response and the biological action of adipose tissue is still largely unknown. Elucidation of these facets may lead to the enhanced efficacy of current treatment options or the identification of novel methods to combat cancer in the obese tumour microenvironment.
Does Modern Lifestyle Favor Neuroimmunometabolic Changes? A Path to Obesity.
Marques Camila Guazzelli,Dos Santos Quaresma Marcus V L,Nakamoto Fernanda Patti,Magalhães Ana Carolina Oumatu,Lucin Glaice Aparecida,Thomatieli-Santos Ronaldo Vagner
Frontiers in nutrition
Factors linked to modern lifestyles, such as physical inactivity, Western diet, and poor sleep quality have been identified as key contributors to the positive energy balance (PEB). PEB rises adipose tissue hypertrophy and dysfunction over the years, affecting cells and tissues that are metabolically critical for energy homeostasis regulation, especially skeletal muscle, hypothalamic-pituitary-adrenal axis, and gut microbiota. It is known that the interaction among lifestyle factors and tissue metabolic dysfunction increases low-grade chronic systemic inflammation, leading to insulin resistance and other adverse metabolic disorders. Although immunometabolic mechanisms are widely discussed in obesity, neuroimmunoendocrine pathways have gained notoriety, as a link to neuroinflammation and central nervous system disorders. Hypothalamic inflammation has been associated with food intake dysregulation, which comprises homeostatic and non-homeostatic mechanisms, promoting eating behavior changes related to the obesity prevalence. The purpose of this review is to provide an updated and integrated perspective on the effects of Western diet, sleep debt, and physical exercise on the regulation of energy homeostasis and low-grade chronic systemic inflammation. Subsequently, we discuss the intersection between systemic inflammation and neuroinflammation and how it can contribute to energy imbalance, favoring obesity. Finally, we propose a model of interactions between systemic inflammation and neuroinflammation, providing new insights into preventive and therapeutic targets for obesity.
Aging, obesity, sarcopenia and the effect of diet and exercise intervention.
The number of adults 65 years and older is increasing worldwide and will represent the 20% of the population by 2030. Half of them will suffer from obesity. The decline in muscle mass and strength, known as sarcopenia, is very common among older adults with obesity (sarcopenic obesity). Sarcopenic obesity is strongly associated with frailty, cardiometabolic dysfunction, physical disability, and mortality. Increasing efforts have been hence made to identify effective strategies able to promote healthy aging and curb the obesity pandemic. Among these, lifestyle interventions consisting of diet and exercise protocols have been extensively explored. Importantly, diet-induced weight loss is associated with fat, muscle, and bone mass losses, and may further exacerbate age-related sarcopenia and frailty outcomes in older adults. Successful approaches to induce fat mass loss while preserving lean and bone mass are critical to reduce the aging- and obesity-related physical and metabolic complications and at the same time ameliorate frailty. In this review article, we discuss the most recent evidence on the age-related alterations in adipose tissue and muscle health and on the effect of calorie restriction and exercise approaches for older adults with obesity and sarcopenia, emphasizing the existing gaps in the literature that need further investigation.
Dysregulated resting state functional connectivity and obesity: A systematic review.
Syan Sabrina K,McIntyre-Wood Carly,Minuzzi Luciano,Hall Geoffrey,McCabe Randi E,MacKillop James
Neuroscience and biobehavioral reviews
Obesity has been variously linked to differences in brain functional connectivity in regions associated with reward, emotional regulation and cognition, potentially revealing neural mechanisms contributing to its development and maintenance. This systematic review summarizes and critically appraises the existing literature on differences in resting state functional connectivity (Rs-FC) between overweight and individuals with obesity in relation healthy-BMI controls. Twenty-nine studies were identified and the results consistently support the hypothesis that obesity is associated with differences in Rs-FC. Specifically, obesity/overweight was consistently associated with (i) DMN hypoconnectivity and salience network hyperconnectivity; (ii) increased Rs-FC between the hypothalamus and reward, limbic and salience networks, and decreased Rs-FC between the hypothalamus and cognitive regions; (iii) increased power within regions associated with inhibition/emotional reasoning; (iv) decreased nodal efficiency, degree centrality, and global efficiency. Collectively, the results suggest obesity is associated with disrupted connectivity of brain networks responsible for cognition, reward, self-referential processing and emotional regulation.
Adipocyte NR1D1 dictates adipose tissue expansion during obesity.
The circadian clock component NR1D1 (REVERBα) is considered a dominant regulator of lipid metabolism, with global deletion driving dysregulation of white adipose tissue (WAT) lipogenesis and obesity. However, a similar phenotype is not observed under adipocyte-selective deletion (), and transcriptional profiling demonstrates that, under basal conditions, direct targets of NR1D1 regulation are limited, and include the circadian clock and collagen dynamics. Under high-fat diet (HFD) feeding, mice do manifest profound obesity, yet without the accompanying WAT inflammation and fibrosis exhibited by controls. Integration of the WAT NR1D1 cistrome with differential gene expression reveals broad control of metabolic processes by NR1D1 which is unmasked in the obese state. Adipocyte NR1D1 does not drive an anticipatory daily rhythm in WAT lipogenesis, but rather modulates WAT activity in response to alterations in metabolic state. Importantly, NR1D1 action in adipocytes is critical to the development of obesity-related WAT pathology and insulin resistance.
A Tale of Three Systems: Toward a Neuroimmunoendocrine Model of Obesity.
Annual review of cell and developmental biology
The prevalence of obesity is on the rise. What was once considered a simple disease of energy imbalance is now recognized as a complex condition perpetuated by neuro- and immunopathologies. In this review, we summarize the current knowledge of the neuroimmunoendocrine mechanisms underlying obesity. We examine the pleiotropic effects of leptin action in addition to its established role in the modulation of appetite, and we discuss the neural circuitry mediating leptin action and how this is altered with obesity, both centrally (leptin resistance) and in adipose tissues (sympathetic neuropathy). Finally, we dissect the numerous causal and consequential roles of adipose tissue macrophages in obesity and highlight recent key studies demonstrating their direct role in organismal energy homeostasis.
Obesity-Associated Mutations and the Melanocortin Pathway.
The New England journal of medicine
BACKGROUND: encodes the Gα (stimulatory G-protein alpha subunit) protein, which mediates G protein-coupled receptor (GPCR) signaling. mutations cause developmental delay, short stature, and skeletal abnormalities in a syndrome called Albright's hereditary osteodystrophy. Because of imprinting, mutations on the maternal allele also cause obesity and hormone resistance (pseudohypoparathyroidism). METHODS:We performed exome sequencing and targeted resequencing in 2548 children who presented with severe obesity, and we unexpectedly identified 22 mutation carriers. We investigated whether the effect of mutations on melanocortin 4 receptor (MC4R) signaling explains the obesity and whether the variable clinical spectrum in patients might be explained by the results of molecular assays. RESULTS:Almost all mutations impaired MC4R signaling. A total of 6 of 11 patients who were 12 to 18 years of age had reduced growth. In these patients, mutations disrupted growth hormone-releasing hormone receptor signaling, but growth was unaffected in carriers of mutations that did not affect this signaling pathway (mean standard-deviation score for height, -0.90 vs. 0.75, respectively; P = 0.02). Only 1 of 10 patients who reached final height before or during the study had short stature. mutations that impaired thyrotropin receptor signaling were associated with developmental delay and with higher thyrotropin levels (mean [±SD], 8.4±4.7 mIU per liter) than those in 340 severely obese children who did not have mutations (3.9±2.6 mIU per liter; P = 0.004). CONCLUSIONS:Because pathogenic mutations may manifest with obesity alone, screening of children with severe obesity for deficiency may allow early diagnosis, improving clinical outcomes, and melanocortin agonists may aid in weight loss. mutations that are identified by means of unbiased genetic testing differentially affect GPCR signaling pathways that contribute to clinical heterogeneity. Monogenic diseases are clinically more variable than their classic descriptions suggest. (Funded by Wellcome and others.).
Inhibition of phosphodiesterase type 9 reduces obesity and cardiometabolic syndrome in mice.
The Journal of clinical investigation
Central obesity with cardiometabolic syndrome (CMS) is a major global contributor to human disease, and effective therapies are needed. Here, we show that cyclic GMP-selective phosphodiesterase 9A inhibition (PDE9-I) in both male and ovariectomized female mice suppresses preestablished severe diet-induced obesity/CMS with or without superimposed mild cardiac pressure load. PDE9-I reduces total body, inguinal, hepatic, and myocardial fat; stimulates mitochondrial activity in brown and white fat; and improves CMS, without significantly altering activity or food intake. PDE9 localized at mitochondria, and its inhibition in vitro stimulated lipolysis in a PPARα-dependent manner and increased mitochondrial respiration in both adipocytes and myocytes. PPARα upregulation was required to achieve the lipolytic, antiobesity, and metabolic effects of PDE9-I. All these PDE9-I-induced changes were not observed in obese/CMS nonovariectomized females, indicating a strong sexual dimorphism. We found that PPARα chromatin binding was reoriented away from fat metabolism-regulating genes when stimulated in the presence of coactivated estrogen receptor-α, and this may underlie the dimorphism. These findings have translational relevance given that PDE9-I is already being studied in humans for indications including heart failure, and efficacy against obesity/CMS would enhance its therapeutic utility.
Obesity, POMC, and POMC-processing Enzymes: Surprising Results From Animal Models.
Lindberg Iris,Fricker Lloyd D
Peptides derived from proopiomelanocortin (POMC) are well-established neuropeptides and peptide hormones that perform multiple functions, including regulation of body weight. In humans and some animals, these peptides include α- and β-melanocyte-stimulating hormone (MSH). In certain rodent species, no β-MSH is produced from POMC because of a change in the cleavage site. Enzymes that convert POMC into MSH include prohormone convertases (PCs), carboxypeptidases (CPs), and peptidyl-α-amidating monooxygenase (PAM). Humans and mice with inactivating mutations in either PC1/3 or carboxypeptidase E (CPE) are obese, which was assumed to result from defective processing of POMC into MSH. However, recent studies have shown that selective loss of either PC1/3 or CPE in POMC-expressing cells does not cause obesity. These findings suggest that defects in POMC processing cannot alone account for the obesity observed in global PC1/3 or CPE mutants. We propose that obesity in animals lacking PC1/3 or CPE activity depends, at least in part, on deficient processing of peptides in non-POMC-expressing cells either in the brain and/or the periphery. Genetic background may also contribute to the manifestation of obesity.
Potential role of anti-inflammatory HDL subclasses in metabolic unhealth/obesity.
Tang Hongjuan,Xiang Zhicong,Li Longyu,Shao Xiaofei,Zhou Qin,You Xu,Xiong Chongxiang,Ning Jing,Chen Tong,Deng David,Zou Hequn
Artificial cells, nanomedicine, and biotechnology
High-density lipoprotein (HDL) particles comprising heterogeneous subclasses of different functions exert anti-inflammatory effects by interacting with immune-response cells. However, the relationship of HDL subclasses with immune-response cells in metabolic unhealth/obesity has not been defined clearly. The purpose of this study was to delineate the relational changes of HDL subclasses with immune cells and inflammatory markers in metabolic unhealth/obesity to understand the role of anti-inflammatory HDL subclasses. A total of 316 participants were classified by metabolic health. HDL subclasses were detected by microfluidic chip electrophoresis. White blood cell (WBC) counts and lymphocytes were assessed using automatic haematology analyser. Levels of high-sensitivity C-reactive protein (hs-CRP) and interleukin 6 (IL-6) were measured. In our study, not only the distribution of HDL subclasses, but also HDL-related structural proteins changed with the deterioration of metabolic disease. Moreover, lymphocytes and inflammation factors significantly gradually increased. The level of HDL2b was negatively associated with WBC, lymphocytes and hs-CRP in multivariable linear regression analysis. In multinomial logistic regression analysis, high levels of HDL3 and low levels of HDL2b increased the probability of having an unfavourable metabolic unhealth/obesity status. We supposed that HDL2b particles may play anti-inflammation by negatively regulating lymphocytes activation. HDL2b may be a therapeutic target for future metabolic disease due to the anti-inflammatory effects.