Association Between Obesity and Cardiovascular Outcomes: A Systematic Review and Meta-analysis of Mendelian Randomization Studies. Riaz Haris,Khan Muhammad Shahzeb,Siddiqi Tariq Jamal,Usman Muhammad Shariq,Shah Nishant,Goyal Amit,Khan Sadiya S,Mookadam Farouk,Krasuski Richard A,Ahmed Haitham JAMA network open Importance:Although dyslipidemia has been consistently shown to be associated with atherogenesis, an association between obesity and cardiovascular disease outcomes remains controversial. Mendelian randomization can minimize confounding if variables are randomly and equally distributed in the population of interest. Objective:To assess evidence from mendelian randomization studies to provide a less biased estimate of any association between obesity and cardiovascular outcomes. Data Sources:Systematic searches of MEDLINE and Scopus from database inception until January 2018, supplemented with manual searches of the included reference lists. Study Selection:Studies that used mendelian randomization methods to assess the association between any measure of obesity and the incidence of cardiovascular events and those that reported odds ratios (ORs) with 95% CIs estimated using an instrumental variable method were included. The 5 studies included in the final analysis were based on a consensus among 3 authors. Data Extraction and Synthesis:Two investigators independently extracted study characteristics using a standard form and pooled data using a random-effects model. The Meta-analysis of Observational Studies in Epidemiology (MOOSE) reporting guideline was followed. Main Outcomes and Measures:Obesity associated with type 2 diabetes, coronary artery disease, or stroke. The hypothesis was formulated prior to data collection. Results:Of 4660 potentially relevant articles, 2511 titles were screened. Seven studies were included in the systematic review, and 5 studies with 881 692 participants were eligible to be included in the meta-analysis. Pooled estimates revealed that obesity was significantly associated with an increased risk of type 2 diabetes (OR, 1.67; 95% CI, 1.30-2.14; P < .001; I2 = 93%) and coronary artery disease (OR, 1.20; 95% CI, 1.02-1.41; P = .03; I2 = 87%). No association between obesity and stroke was found (OR, 1.02; 95% CI, 0.95-1.09; P = .65; I2 = 0%). Conclusions and Relevance:The present meta-analysis suggests that obesity is associated with type 2 diabetes and coronary artery disease. Although this analysis of mendelian randomization studies does not prove causality, it is supportive of a causal association. Hence, health care practitioners should continue to emphasize weight reduction to combat coronary artery disease. 10.1001/jamanetworkopen.2018.3788
    Translational Significance of Heme Oxygenase in Obesity and Metabolic Syndrome. Abraham Nader G,Junge Joshua M,Drummond George S Trends in pharmacological sciences The global epidemic of obesity continues unabated with sequelae of diabetes and metabolic syndrome. This review reflects the dramatic increase in research on the role of increased expression of heme oxygenase (HO)-1/HO-2, biliverdin reductase, and HO activity on vascular disease. The HO system engages with other systems to mitigate the deleterious effects of oxidative stress in obesity and cardiovascular disease (CVD). Recent reports indicate that HO-1/HO-2 protein expression and HO activity have several important roles in hemostasis and reactive oxygen species (ROS)-dependent perturbations associated with metabolic syndrome. HO-1 protects tissue during inflammatory stress in obesity through the degradation of pro-oxidant heme and the production of carbon monoxide (CO) and bilirubin, both of which have anti-inflammatory and anti-apoptotic properties. By contrast, repression of HO-1 is associated with increases of cellular heme and inflammatory conditions including hypertension, stroke, and atherosclerosis. HO-1 is a major focus in the development of potential therapeutic strategies to reverse the clinical complications of obesity and metabolic syndrome. 10.1016/j.tips.2015.09.003
    Update on Obesity and Obesity Paradox in Heart Failure. Lavie Carl J,Sharma Abhishek,Alpert Martin A,De Schutter Alban,Lopez-Jimenez Francisco,Milani Richard V,Ventura Hector O Progress in cardiovascular diseases Obesity has reached epidemic proportions in most of the Westernized world. Overweightness and obesity adversely impact cardiac structure and function, including on both the right and, especially, left sides of the heart, with adverse affects on systolic and, especially, diastolic ventricular function. Therefore, it is not surprising that obesity markedly increases the prevalence of heart failure (HF). Nevertheless, many studies have documented an obesity paradox in large cohorts with HF, where overweight and obese have a better prognosis, at least in the short-term, compared with lean HF patients. Although weight loss clearly improves cardiac structure and function and reduces symptoms in HF, there are no large studies on the impact of weight loss on clinical events in HF, preventing definitive guidelines on optimal body composition in patients with HF. 10.1016/j.pcad.2015.12.003
    Facing Morbid Obesity: How to Approach It. Ricci Maria Anastasia,De Vuono Stefano,Scavizzi Matteo,Gentili Alessandra,Lupattelli Graziana Angiology Obesity is a major public health problem, with a prevalence of 10% to 20% in Western Europe. Morbid obesity, characterized by body mass index >40 kg/m(2), showed an increased prevalence in the last 30 years. Obesity is associated with reduced economic and social opportunities, reduced quality of life, and is a determinant of several "intermediate risk factors," leading to an increased mortality and a loss in life expectancy. The rising prevalence of morbid obesity increased the demand for bariatric surgery, also called "metabolic surgery": after these interventions, there is a decrease in metabolic comorbidities, cardiovascular (CV) risk, and total mortality. In this review, we update the evaluation of morbid obese patients from the physical examination to the metabolic, CV and respiratory assessments in order to correctly stratify the CV risk and provide the best treatment. To obtain these achievements, multidisciplinary work has to be carried out with a team involving several experts with different skills. 10.1177/0003319715595735
    Cardiovascular and Metabolic Heterogeneity of Obesity: Clinical Challenges and Implications for Management. Neeland Ian J,Poirier Paul,Després Jean-Pierre Circulation The prevalence of obesity has increased globally over the last 2 decades. Although the body mass index has been a convenient and simple index of obesity at the population level, studies have shown that obesity defined by body mass index alone is a remarkably heterogeneous condition with varying cardiovascular and metabolic manifestations across individuals. Adipose tissue is an exquisitely active metabolic organ engaged in cross-talk between various systems; perturbation of adipose tissue results in a pathological response to positive caloric balance in susceptible individuals that directly and indirectly contributes to cardiovascular and metabolic disease. Inadequate subcutaneous adipose tissue expansion in the face of dietary triglycerides leads to visceral and ectopic fat deposition, inflammatory/adipokine dysregulation, and insulin resistance. Conversely, preferential fat storage in the lower body depot may act as a metabolic buffer and protect other tissues from lipotoxicity caused by lipid overflow and ectopic fat. Translational, epidemiological, and clinical studies over the past 30 years have clearly demonstrated a strong link between visceral and ectopic fat and the development of a clinical syndrome characterized by atherogenic dyslipidemia, hyperinsulinemia/glucose intolerance, hypertension, atherosclerosis, and adverse cardiac remodeling/heart failure. This relationship is even more nuanced when clinical entities such as metabolically healthy obesity phenotype and the obesity paradox are considered. Although it is clear that the accumulation of visceral/ectopic fat is a major contributor to cardiovascular and metabolic risk above and beyond the body mass index, implementation of fat distribution assessment into clinical practice remains a challenge. Anthropometric indexes of obesity are easily implemented, but newer imaging-based methods offer improved sensitivity and specificity for measuring specific depots. Lifestyle, pharmacological, and surgical interventions allow a multidisciplinary approach to overweight/obesity that may improve outcomes and align with a public health message to combat the growing epidemic of obesity worldwide and to build healthier lives free of cardiovascular diseases. 10.1161/CIRCULATIONAHA.117.029617
    Obesity and cardiovascular disease: friend or foe? Kim Seong Hwan,Després Jean-Pierre,Koh Kwang Kon European heart journal Obesity is currently one of the greatest public health issues worldwide. However, despite its known deleterious effects on the cardiovascular system and its association with numerous cardiovascular diseases (CVD), recent findings leading to the development of concepts such as metabolically healthy obesity, the obesity paradox, and protective subcutaneous fat depots have raised a lively debate on the disparate effects of obesity on health outcomes. Regarding the concept of metabolically healthy obesity, by presumably labelling a subset of obese people as metabolically healthy, physicians may not feel pressed to curb the current obesity epidemic and prevent the next generation of people from becoming obese. Another issue is that the most commonly used anthropometric index to define obesity, the body mass index, is at the core of the controversy because of its limitations including its inability to discriminate between fat mass and muscle mass. Many recent epidemiological and metabolic studies have used other indices such as waist-hip ratio, waist circumference, and imaging (computed tomography or magnetic resonance imaging) measurements of visceral adiposity and of ectopic fat depots. In addition, emerging evidence supports the importance of cardiorespiratory fitness, skeletal muscle mass and strength in patients with obesity as useful variables to predict CVD risk beyond adiposity. In this review, we will discuss the complex and disparate effects of obesity on CVD, particularly focusing on whether, under given circumstances, it could be harmful, potentially harmless or neutral, or even possibly protective. 10.1093/eurheartj/ehv509
    Emerging Concepts Linking Obesity with the Hallmarks of Cancer. Donohoe Claire L,Lysaght Joanne,O'Sullivan Jacintha,Reynolds John V Trends in endocrinology and metabolism: TEM There is compelling epidemiological evidence linking obesity to many tumours; however, the molecular mechanisms fuelling this association are not clearly understood. Emerging evidence links changes in the tumour microenvironment with the obese state, and murine and human studies highlight the relevance of adipose stromal cells (ASCs), including immune cells, both at remote fat depots, such as the omentum, as well as in peritumoural tissue. These obesity-associated changes have been implicated in several hallmarks of cancer, including the chronic inflammatory state and associated cell signalling, epithelial-to-mesenchymal transition (EMT), tumour-related fibrosis, angiogenesis, and genomic instability. Here, we present a summary of developments over the past 5 years, with particular focus on the tumour microenvironment in the obese state. 10.1016/j.tem.2016.08.004
    Adipokines at the crossroad between obesity and cardiovascular disease. Molica Filippo,Morel Sandrine,Kwak Brenda R,Rohner-Jeanrenaud Françoise,Steffens Sabine Thrombosis and haemostasis Obesity, and especially excessive visceral adipose tissue accumulation, is considered as a low-grade inflammatory state that is responsible for adipocyte dysfunction and associated metabolic disorders. Adipose tissue displays endocrine functions by releasing pro- or anti-inflammatory bioactive molecules named adipokines. An altered expression of these molecules, provoked by obesity or adipocyte dysregulation, contributes to major metabolic diseases such as insulin resistance and type 2 diabetes mellitus that are important risk factors for cardiovascular disease. However, obesity is also characterised by the expansion of perivascular adipose tissue that acts locally via diffusion of adipokines into the vascular wall. Local inflammation within blood vessels induced by adipokines contributes to the onset of endothelial dysfunction, atherosclerosis and thrombosis, but also to vascular remodelling and hypertension. A fast expansion of obesity is expected in the near future, which will rapidly increase the incidence of these cardiovascular diseases. The focus of this review is to summarise the link between metabolic and cardiovascular disease and discuss current treatment approaches, limitations and future perspectives for more targeted therapies. 10.1160/TH14-06-0513
    Vascular risk in obesity: Facts, misconceptions and the unknown. King Rhodri J,Ajjan Ramzi A Diabetes & vascular disease research Obesity is a major burden on healthcare systems worldwide due to the association with numerous complications, arguably the most important of which are the development of type 2 diabetes and cardiovascular disease. Both are thought to develop from similar origins and occur at variable rates in obese individuals, including those with similar body mass indices. This phenomenon is likely a result of an increased susceptibility for the storage of excess fat in the wrong place, namely, ectopic fat surrounding the liver, pancreas and muscles. This triggers a concatenation of events leading to insulin resistance and inflammation which culminate in an increased atherothrombotic potential due to the dysfunction of vascular endothelial cells causing accelerated atherosclerotic plaque formation and a pro-thrombotic phenotype. The degree of weight loss following different interventions is well documented but it is less widely known what effect weight loss by various means has on the deleterious process mentioned above, in particular their effects on cardiovascular events. This review summarises the processes leading to increased vascular risk in obesity and examines the effects of currently available weight loss strategies on reversing these processes and how this translates to cardiovascular disease. 10.1177/1479164116675488
    Obesity and the "obesity paradox" in cardiovascular diseases. Lavie C J,Milani R V,Ventura H O Clinical pharmacology and therapeutics Obesity adversely affects most cardiovascular (CV) risk factors and is strongly associated, probably as an independent risk factor, with most CV diseases. However, substantial evidence points to the existence of an "obesity paradox," in that overweight and obese patients with established CV diseases typically have a better prognosis than leaner patients with the same CV disease. Despite this paradox, we believe that the "weight" of evidence still supports efforts at purposeful weight loss in both primary and secondary CV prevention. 10.1038/clpt.2011.87
    The single use of body mass index for the obesity paradox is misleading and should be used in conjunction with other obesity indices. Chrysant Steven G,Chrysant George S Postgraduate medicine Overweight and obesity in children and adults have significantly risen in the US and worldwide due to biological, environmental, and cultural drivers and account for about 2.1 billion people. In addition, obesity, even metabolically healthy, is a major risk factor for the metabolic syndrome, diabetes mellitus, dyslipidemia, and hypertension, all significant causes of cardiovascular disease (CVD), coronary heart disease (CHD) heart failure (HF) and stroke. However, despite these causative effects, overweight and obesity frequently, confer protection in patients with established CVD, CHD, HF, and hypertension, compared to normal weight persons, the so-called 'obesity paradox'. This phenomenon though is not unique, because other studies have not shown a protective effect of overweight and obesity in such patients. These controversial effects of obesity are mostly due to the use of different indices of obesity by the various studies. Most studies have used the body mass index (BMI) as an index of obesity, which is a poor index for total fat or fat distribution. In order to get a better perspective on the true nature of the obesity paradox, a Medline and Embase search of the English language literature was contacted from 2012 to 2018, using the terms, overweight, obesity, obesity paradox, CVD, HF, and hypertension. From this search, 37 pertinent papers were selected and their findings together with collateral literature will be discussed in this review. The analysis of data suggests that the existence of the obesity paradox is questionable based on the single use of BMI as a measure of obesity. The use of waist circumference and waist to hip ratio are better indices of obesity and should be used together with the BM. 10.1080/00325481.2019.1568019
    The obesity paradox: is it really a paradox? Hypertension. Lechi Alessandro Eating and weight disorders : EWD This article is a narrative overview of the role of hypertension on the relationships between obesity, morbidity, and mortality. We used as sources MEDLINE/PubMed, CINAHL, EMBASE, and Cochrane Library, from inception to March 2016. Key words include overweight, obesity, visceral obesity, obesity paradox, and hypertension. In addition, we hand-searched references from the retrieved articles. This work is one of the works of the topical collection "Obesity Paradox". The positive association between overweight, obesity, and cardiovascular diseases is well established, though this relation is typically U shaped with an increased risk in low-weight subjects or even a beneficial effect of overweight and obesity, the so-called "obesity paradox". In addition, the relationship between obesity and arterial hypertension has been demonstrated in both children and adults by many epidemiological studies. Moreover, weight reduction is followed by a decrease in blood pressure in many patients and ameliorates the cardiovascular risk profile. Recent studies using more appropriate obesity indices raise some doubt about the real significance of obesity paradox and there are several studies that central obesity shows either no protective or even a worse effect. These observations raise the question: what kind of obesity is protective and what kind of obesity is harmful? The studies of obesity paradox suffer from several methodological limitations: most of these are retrospective analyses or were not specifically designed to study obesity paradox as a primary goal; a few studies have data on preceding unintentional weight loss and on some particular confounding variables. In conclusion, more prospective and accurate studies are necessary to better elucidate the clinical importance of obesity paradox. When weight loss is functional to reduce hypertension and cardiovascular risk, it should be encouraged, while an unintentional weight in a patient with chronic diseases may indicate an unfavorable course. 10.1007/s40519-016-0330-4
    Obesity in Low- and Middle-Income Countries: Burden, Drivers, and Emerging Challenges. Ford Nicole D,Patel Shivani A,Narayan K M Venkat Annual review of public health We have reviewed the distinctive features of excess weight, its causes, and related prevention and management efforts, as well as data gaps and recommendations for future research in low- and middle-income countries (LMICs). Obesity is rising in every region of the world, and no country has been successful at reversing the epidemic once it has begun. In LMICs, overweight is higher in women compared with men, in urban compared with rural settings, and in older compared with younger individuals; however, the urban-rural overweight differential is shrinking in many countries. Overweight occurs alongside persistent burdens of underweight in LMICs, especially in young women. Changes in the global diet and physical activity are among the hypothesized leading contributors to obesity. Emerging risk factors include environmental contaminants, chronic psychosocial stress, neuroendocrine dysregulation, and genetic/epigenetic mechanisms. Data on effective strategies to prevent the onset of obesity in LMICs or elsewhere are limited. Expanding the research in this area is a key priority and has important possibilities for reverse innovation that may also inform interventions in high-income countries. 10.1146/annurev-publhealth-031816-044604
    Causal inference in obesity research. Franks P W,Atabaki-Pasdar N Journal of internal medicine Obesity is a risk factor for a plethora of severe morbidities and premature death. Most supporting evidence comes from observational studies that are prone to chance, bias and confounding. Even data on the protective effects of weight loss from randomized controlled trials will be susceptible to confounding and bias if treatment assignment cannot be masked, which is usually the case with lifestyle and surgical interventions. Thus, whilst obesity is widely considered the major modifiable risk factor for many chronic diseases, its causes and consequences are often difficult to determine. Addressing this is important, as the prevention and treatment of any disease requires that interventions focus on causal risk factors. Disease prediction, although not dependent on knowing the causes, is nevertheless enhanced by such knowledge. Here, we provide an overview of some of the barriers to causal inference in obesity research and discuss analytical approaches, such as Mendelian randomization, that can help to overcome these obstacles. In a systematic review of the literature in this field, we found: (i) probable causal relationships between adiposity and bone health/disease, cancers (colorectal, lung and kidney cancers), cardiometabolic traits (blood pressure, fasting insulin, inflammatory markers and lipids), uric acid concentrations, coronary heart disease and venous thrombosis (in the presence of pulmonary embolism), (ii) possible causal relationships between adiposity and gray matter volume, depression and common mental disorders, oesophageal cancer, macroalbuminuria, end-stage renal disease, diabetic kidney disease, nuclear cataract and gall stone disease, and (iii) no evidence for causal relationships between adiposity and Alzheimer's disease, pancreatic cancer, venous thrombosis (in the absence of pulmonary embolism), liver function and periodontitis. 10.1111/joim.12577
    Metabolically healthy obesity and cardiovascular events: A systematic review and meta-analysis. Eckel Nathalie,Meidtner Karina,Kalle-Uhlmann Tamara,Stefan Norbert,Schulze Matthias B European journal of preventive cardiology AIMS:Previous studies have provided inconsistent results about the cardiovascular risks for participants with metabolically healthy obesity (MHO). These uncertainties might partly reflect the lack of a uniform definition of MHO. We conducted a systematic review and meta-analysis to examine whether there is a suitable approach that identifies obese participants who are not at an increased risk of cardiovascular events compared with healthy normal-weight participants. METHODS AND RESULTS:Twenty-two prospective studies were eligible for the meta-analysis. Using random-effect models, pooled relative risks (RRs) were calculated for the combined effects of obesity with the presence or absence of metabolic syndrome, insulin resistance, hypertension, diabetes, hyperlipidaemia and any of these metabolic factors. Participants with MHO defined by the absence of metabolic syndrome were at increased risk for cardiovascular events compared with healthy normal-weight participants (pooled RR 1.45, 95% confidence interval (CI) 1.20-1.70), but had lower risks than unhealthy normal-weight (RR 2.07, 95% CI 1.62-2.65) and obese (RR 2.31, 95% CI 1.99-2.69) participants. The risk associated with participants who had MHO was particularly high over the long term. Similar risk estimates were observed when MHO was defined by other approaches. CONCLUSIONS:None of the approaches clearly identified an obese subgroup not at increased risk of cardiovascular events compared with normal-weight healthy participants. A benign obese phenotype might be defined by strict definitions, but insufficient studies exist to support this. More research is needed to better define MHO. 10.1177/2047487315623884
    Precision Medicine in Obesity and Type 2 Diabetes: The Relevance of Early-Life Exposures. Estampador Angela C,Franks Paul W Clinical chemistry BACKGROUND:Type 2 diabetes is highly prevalent and devastating. Obesity is a diabetogenic factor, driving insulin resistance and a compensatory demand for increased insulin secretion from the pancreatic β cells; a failure to address this demand results in diabetes. Accordingly, primary and secondary prevention of obesity are at the core of diabetes prevention programs. The development of obesity and declining β-cell function often span many years or decades before diabetes is clinically manifest. Thus, characterizing the early-life process and risk factors that set disease trajectories may yield novel targets for early intervention and help improve the accuracy of prediction algorithms, factors germane to the emerging field of precision medicine. CONTENT:Here, we overview the concepts of precision medicine and fetal programming. We discuss the barriers to preventing obesity and type 2 diabetes in adulthood and present the rationale for considering early-life events in this context. In so doing, we discuss proof-of-concept studies and cutting-edge technological developments that are likely to transform current thinking on the etiology and pathogenesis of obesity and type 2 diabetes. We also review the factors hampering progress, including the success and failures of pregnancy intervention trials. SUMMARY:Obesity and type 2 diabetes are among the major health and economic burdens of our time. Defeating these diseases is likely to require life-course approaches, which may include aggressive interventions informed by biomarker profiling undertaken during early life. 10.1373/clinchem.2017.273540
    The Impact of Obesity on Medical Care Costs and Labor Market Outcomes in the US. Biener Adam,Cawley John,Meyerhoefer Chad Clinical chemistry BACKGROUND:The prevalence of obesity has risen dramatically in most countries of the world, and the economic consequences of obesity are not well understood. METHODS:We analyzed data from the Medical Expenditure Panel Survey (MEPS) for 2001-2015 and estimated the percentage of healthcare costs that were associated with adult obesity, both for the US as a whole and for the most populous states. We also reviewed the literature on the impact of obesity on economic outcomes such as medical care costs, employment, and wages. RESULTS:The percent of US national medical expenditures devoted to treating obesity-related illness in adults rose from 6.13% in 2001 to 7.91% in 2015, an increase of 29%. Substantial differences existed across states; in 2015, some states (AZ, CA, FL, NY) devoted 5%-6% of medical expenditures to obesity, whereas others (NC, OH, WI) spent >12% of all healthcare dollars on obesity. A review of previous literature that exploited natural experiments to estimate causal effects found that obesity raises medical care costs and lowers wages and the probability of employment. CONCLUSIONS:A substantial and rising percentage of healthcare costs are associated with obesity. This is true for the US, for individual states, for each category of expenditure, and for each type of payer. Previous literature generally found that obesity worsens economic outcomes, such as medical care costs, wages, and employment, and imposes negative external costs that may justify government intervention. 10.1373/clinchem.2017.272450
    Adipokines demonstrate the interacting influence of central obesity with other cardiometabolic risk factors of metabolic syndrome in Hong Kong Chinese adults. Supriya Rashmi,Tam Bjorn T,Yu Angus P,Lee Paul H,Lai Christopher W,Cheng Kenneth K,Yau Sonata Y,Chan Lawrence W,Yung Benjamin Y,Sheridan Sinead,Siu Parco M PloS one OBJECTIVE:Metabolic syndrome (MetS) or prediabetes is a complex disorder that is defined by a clustering of cardiometabolic risk factors, including obesity, hypertriglyceridemia, reduced high-density lipoprotein (HDL) cholesterol, hypertension, and insulin resistance. Among cardiometabolic risk factors, central obesity plays a key role in the development of MetS through alterations in the secretion of adipokines and interacts with other MetS risk factors to unfavorably influence overall cardiometabolic risk. Obesity has grasped epidemic proportions in Asia, which has the highest number of people with diabetes in the world. But, the importance of central obesity in the clustering of all four MetS risk factors or vice versa in predicting severity of MetS has not yet been investigated in Asian population. Therefore, the present study examined the influence of central obesity on circulating levels of adipokines through its interaction with the clustering of cardiometabolic risk factors of MetS including hyperglycemia, hypertriglyceridemia, dyslipidemia and hypertension in Hong Kong Chinese adults. SUBJECTS:Blood samples from 83 Hong Kong Chinese adults, who were previously screened for MetS according to the guideline of the United States National Cholesterol Education Program Expert Panel Adult Treatment Panel III criteria were selected. Insulin and adipokines, including visfatin, chemerin, plasminogen activator inhibitor-1 (PAI-1), resistin, C-C motif chemokine ligand 2 (CCL-2), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10), tumour necrosis factor-α (TNF-α), leptin and adiponectin were assessed. RESULTS:The interacting effect of central obesity with all of the other four MetS risk factors increased the proinflammatory status of adipokines (TNF-α, leptin) and decreased the anti-inflammatory status of adipokine (adiponectin). CONCLUSION:Our results indicate that the inflammatory status of MetS may be more severe in the presence of central obesity. Adipokines, as biomarkers for pathophysiological changes, may help to improve early patient identification and to predict MetS-associated morbidity and mortality. 10.1371/journal.pone.0201585
    [Inflammatory biomarkers: the link between obesity and associated pathologies]. Zulet Ma A,Puchau B,Navarro C,Martí A,Martínez J A Nutricion hospitalaria THE OBJECTIVE:[corrected] of this article is to review biomarkers that have been suggested in recent years as the link between inflammation, obesity and associated co-morbidities, as well as some questions that yet remain unclear. Increasing evidence indicates the important role of inflammation in the etiology of major public health problems. In the last years, several studies have proposed that obesity might be a inflammatory disorder. In addition, oxidative stress has been suggested as a potential inductor of inflammatory status and susceptibility to obesity and related disorders. Several biomarkers are being suggested as the link between obesity, insulin resistance, cardiovascular disease and metabolic syndrome, such as tumor necrosis factor alfa, interleukin-6 and -18, angiotensinogen, transforming grow factor beta, plasminogen activator inhibitor-1, leptin, resistin, C-reactive protein, serum amyloid A, sialic acid, fibrinogen, markers of endothelial dysfunction (von Willebrand factor, ICAMs, VCAMs), complement factor 3, haptoglobin, Zinc-alpha2-glycoprotein, eotaxin, visfatin, apelin, alpha1-antitrypsin, vaspin, omentin, retinol binding protein 4, ceruloplasmin, adiponectin and desnutrin. Some of this biomarkers are good predictors of cardiovascular risk (plasminogen activator inhibitor-1, sialic acid, fribrinogen, complement factor 3, C-reactive protein), adiposity (leptin, visfatin, resistin, haptoglobin) and/or insulin resistance (sialic acid, C-reactive protein, plasminogen activator inhibitor-1, von Willebrand factor). However, it is currently unclear the role of many of them concerning inflammatory processes in humans, as well as the factors involved in their regulation.
    Addressing the Perfect Storm: Biomarkers in Obesity and Pathophysiology of Cardiometabolic Risk. Aleksandrova Krasimira,Mozaffarian Dariush,Pischon Tobias Clinical chemistry BACKGROUND:The worldwide rise of obesity has provoked intensified research to better understand its pathophysiology as a means for disease prevention. Several biomarkers that may reflect various pathophysiological pathways that link obesity and cardiometabolic diseases have been identified over the past decades. CONTENT:We summarize research evidence regarding the role of established and novel obesity-related biomarkers, focusing on recent epidemiological evidence for detrimental associations with cardiometabolic diseases including obesity-related cancer. The reviewed biomarkers include biomarkers of glucose-insulin homeostasis (insulin, insulin-like growth factors, and C-peptide), adipose tissue biomarkers (adiponectin, omentin, apelin, leptin, resistin, and fatty-acid-binding protein-4), inflammatory biomarkers (C-reactive protein, interleukin 6, tumor necrosis factor α), and omics-based biomarkers (metabolites and microRNAs). SUMMARY:Although the evidence for many classical obesity biomarkers, including adiponectin and C-reactive protein (CRP), in disease etiology has been initially promising, the evidence for a causal role in humans remains limited. Further, there has been little demonstrated ability to improve disease prediction beyond classical risk factors. In the era of "precision medicine," there is an increasing interest in novel biomarkers, and the extended list of potentially promising biomarkers, such as adipokines, cytokines, metabolites, and microRNAs, implicated in obesity may bring new promise for improved, personalized prevention. To further evaluate the role of obesity-related biomarkers as etiological and early-disease-prediction targets, well-designed studies are needed to evaluate temporal associations, replicate findings, and test clinical utility of novel biomarkers. In particular, studies to determine the therapeutic implications of novel biomarkers beyond established metabolic risk factors are highly warranted. 10.1373/clinchem.2017.275172
    Determining the cost of obesity and its common comorbidities from a commercial claims database. Padula W V,Allen R R,Nair K V Clinical obesity What is already known about this subject Obesity is highly prevalent and costly in the US. Obesity often leads to other comorbid conditions, including diabetes and hypertension. Obesity prevention efforts can reduce healthcare costs. What this study adds Obesity combined with other comorbidities significantly increases healthcare costs per patient visit. The combination of obesity and depression exacerbates costs. The most expensive series of chronic conditions in this study included obesity, diabetes, hypertension and depression. Our objectives were to determine payments made by commercial healthcare providers in the US for adults diagnosed with obesity, and those comorbid with any combination of selected chronic conditions. Using a commercial claims and encounters database (n = 3,562,717), we evaluated an adult study population that had at least one in-patient visit, outpatient visit or emergency department visit, and received a primary or secondary diagnosis of obesity. Persons were categorized by one or more comorbid diagnoses for diabetes mellitus, hypertension, depression or congestive heart failure. We adjusted for age and gender, and calculated the mean total net expenditures (in 2012, $US) for each combination of comorbid conditions based on individual visits to an in-patient, outpatient or emergency department setting. Among 50,717 claims with diagnosis of obesity, the mean net expenditure for in-patient and outpatient services was $ 1907 per patient per visit. Persons diagnosed with obesity and other comorbidities observed an increase in total net expenditures. Obesity and congestive heart failure observed the highest increase among single comorbidities at $ 5275. For persons with obesity and two other comorbidities, diabetes mellitus and depression was the highest at $ 15,226. The most expensive condition was obesity, diabetes mellitus, hypertension and depression at $ 15,733. Compared with average medical claims, persons diagnosed with obesity and other common chronic conditions experience significant increases in medical costs. These costs are often driven higher by time spent as in-patients. By controlling and reducing the prevalence of obesity, we may see significant decreases in medical expenditures. 10.1111/cob.12041
    Obesity and the metabolic syndrome in developing countries. Misra Anoop,Khurana Lokesh The Journal of clinical endocrinology and metabolism CONTEXT:Prevalence of obesity and the metabolic syndrome is rapidly increasing in developing countries, leading to increased morbidity and mortality due to type 2 diabetes mellitus (T2DM) and cardiovascular disease. EVIDENCE ACQUISITION:Literature search was carried out using the terms obesity, insulin resistance, the metabolic syndrome, diabetes, dyslipidemia, nutrition, physical activity, and developing countries, from PubMed from 1966 to June 2008 and from web sites and published documents of the World Health Organization and Food and Agricultural Organization. EVIDENCE SYNTHESIS:With improvement in economic situation in developing countries, increasing prevalence of obesity and the metabolic syndrome is seen in adults and particularly in children. The main causes are increasing urbanization, nutrition transition, and reduced physical activity. Furthermore, aggressive community nutrition intervention programs for undernourished children may increase obesity. Some evidence suggests that widely prevalent perinatal undernutrition and childhood catch-up obesity may play a role in adult-onset metabolic syndrome and T2DM. The economic cost of obesity and related diseases in developing countries, having meager health budgets is enormous. CONCLUSIONS:To prevent increasing morbidity and mortality due to obesity-related T2DM and cardiovascular disease in developing countries, there is an urgent need to initiate large-scale community intervention programs focusing on increased physical activity and healthier food options, particularly for children. International health agencies and respective government should intensively focus on primordial and primary prevention programs for obesity and the metabolic syndrome in developing countries. 10.1210/jc.2008-1595
    Obesity as a Disease. Upadhyay Jagriti,Farr Olivia,Perakakis Nikolaos,Ghaly Wael,Mantzoros Christos The Medical clinics of North America Obesity is a complex disease with many causal factors, associated with multiple comorbidities that contribute to significant morbidity and mortality. It is a highly prevalent disease that poses an enormous health and economic burden to society. This article reviews the mechanisms of obesity and its related comorbidities. 10.1016/j.mcna.2017.08.004
    Waist-to-height ratio is a better obesity index than body mass index and waist-to-hip ratio for predicting diabetes, hypertension and lipidemia. Sayeed M A,Mahtab H,Latif Z A,Khanam P A,Ahsan K A,Banu A,Azad Khan A K Bangladesh Medical Research Council bulletin Body mass index (BMI, kg/m.sq) and waist-to-hip ratio (WHR) are widely used as obesity indices for diabetes and cardiovascular risks. Lower adult height was related to diabetes and stroke. Waist-girth was proved important for visceral obesity. Incorporating waist-girth and height as waist-to-height ratio (WHtR), we reported earlier--"Waist-to-height ratio is an important predictor of hypertension and diabetes". We readdressed this index in a larger sample with two-sample OGTT and lipid profiles. In a cluster sampling of 16,818 rural inhabitants, considering age > or = 20 y, 5713 subjects were found eligible. Of them, 4923 (M/F=2321/2602) volunteered for height, weight, blood pressure, waist-girth and hip-girth. Fasting venous blood (5 ml) was drawn for plasma glucose, total cholesterol (T-chol), Triglycerides (TG) and high-density lipoprotien (HDL-c). Overall, 1565 participants were undertaken for OGTT. The mean (SD) values of BMI, WHR and WHtR for subjects with diabetes and hypertension were significantly higher in either sex. The level significance was highest for WHtR. The prevalence of diabetes and hypertension increased significantly with higher quintiles of BMI, WHR and WHtR (chi sq values were largest in WHtR for both events). Partial correlation coefficients, controlling for age and sex, showed that BMI, WHR and WHtR significantly correlated with systolic and diastolic BP, FBG, T-chol and TG. In the entire correlation matrix, the 'r' values were the highest for WHtR. Taking diabetes and hypertension as dependent variables, logistic regression also showed the highest odds ratio in higher WHtR than BMI and WHR. We conclude that WHtR was proved again a valuable obesity index for predicting diabetes, hypertension and lipidemia.
    Obesity Paradox in Hypertension: Is This Because Sympathetic Activation in Obesity-Hypertension Takes a Benign Form? Esler Murray,Lambert Gavin,Schlaich Markus,Dixon John,Sari Carolina Ika,Lambert Elisabeth Hypertension (Dallas, Tex. : 1979) 10.1161/HYPERTENSIONAHA.117.09790
    Obesity, inflammation, and atherosclerosis. Rocha Viviane Z,Libby Peter Nature reviews. Cardiology Understanding of the pathophysiology of atherogenesis has evolved substantially during the last few decades. Atherosclerosis was once identified as a lipid-storage disease, but is now recognized as a subacute inflammatory condition of the vessel wall, characterized by infiltration of macrophages and T cells, which interact with one another and with cells of the arterial wall. The pathological mechanisms of obesity recapitulate many features of the inflammatory processes at work in atherosclerosis. Our current appreciation of the similarities between obesity and atherosclerosis has already fostered innovations for the diagnosis, prognosis, and prevention of these two conditions. 10.1038/nrcardio.2009.55
    Lipid signaling in adipose tissue: Connecting inflammation & metabolism. Masoodi Mojgan,Kuda Ondrej,Rossmeisl Martin,Flachs Pavel,Kopecky Jan Biochimica et biophysica acta Obesity-associated low-grade inflammation of white adipose tissue (WAT) contributes to development of insulin resistance and other disorders. Accumulation of immune cells, especially macrophages, and macrophage polarization from M2 to M1 state, affect intrinsic WAT signaling, namely anti-inflammatory and proinflammatory cytokines, fatty acids (FA), and lipid mediators derived from both n-6 and n-3 long-chain PUFA such as (i) arachidonic acid (AA)-derived eicosanoids and endocannabinoids, and (ii) specialized pro-resolving lipid mediators including resolvins derived from both eicosapentaenoic (EPA) and docosahexaenoic acid (DHA), lipoxins (AA metabolites), protectins and maresins (DHA metabolites). In this respect, potential differences in modulating adipocyte metabolism by various lipid mediators formed by inflammatory M1 macrophages typical of obese state, and non-inflammatory M2 macrophages typical of lean state remain to be established. Studies in mice suggest that (i) transient accumulation of M2 macrophages could be essential for the control of tissue FA levels during activation of lipolysis, (ii) currently unidentified M2 macrophage-borne signaling molecule(s) could inhibit lipolysis and re-esterification of lipolyzed FA back to triacylglycerols (TAG/FA cycle), and (iii) the egress of M2 macrophages from rebuilt WAT and removal of the negative feedback regulation could allow for a full unmasking of metabolic activities of adipocytes. Thus, M2 macrophages could support remodeling of WAT to a tissue containing metabolically flexible adipocytes endowed with a high capacity of both TAG/FA cycling and oxidative phosphorylation. This situation could be exemplified by a combined intervention using mild calorie restriction and dietary supplementation with EPA/DHA, which enhances the formation of "healthy" adipocytes. This article is part of a Special Issue entitled Oxygenated metabolism of PUFA: analysis and biological relevance." 10.1016/j.bbalip.2014.09.023
    Adipocytes properties and crosstalk with immune system in obesity-related inflammation. Maurizi Giulia,Della Guardia Lucio,Maurizi Angela,Poloni Antonella Journal of cellular physiology Obesity is a condition likely associated with several dysmetabolic conditions or worsening of cardiovascular and other chronic disturbances. A key role in this mechanism seem to be played by the onset of low-grade systemic inflammation, highlighting the importance of the interplay between adipocytes and immune system cells. Adipocytes express a complex and highly adaptive biological profile being capable to selectively activate different metabolic pathways in order to respond to environmental stimuli. It has been demonstrated how adipocytes, under appropriate stimulation, can easily differentiate and de-differentiate thereby converting themselves into different phenotypes according to metabolic necessities. Although underlying mechanisms are not fully understood, growing in adipocyte size and the inability of storing triglycerides under overfeeding conditions seem to be crucial for the switching to a dysfunctional metabolic profile, which is characterized by inflammatory and apoptotic pathways activation, and by the shifting to pro-inflammatory adipokines secretion. In obesity, changes in adipokines secretion along with adipocyte deregulation and fatty acids release into circulation contribute to maintain immune cells activation as well as their infiltration into regulatory organs. Over the well-established role of macrophages, recent findings suggest the involvement of new classes of immune cells such as T regulatory lymphocytes and neutrophils in the development inflammation and multi systemic worsening. Deeply understanding the pathways of adipocyte regulation and the de-differentiation process could be extremely useful for developing novel strategies aimed at curbing obesity-related inflammation and related metabolic disorders. 10.1002/jcp.25855
    The Role of Chronic Disease, Obesity, and Improved Treatment and Detection in Accounting for the Rise in Healthcare Spending Between 1987 and 2011. Thorpe Kenneth E,Allen Lindsay,Joski Peter Applied health economics and health policy BACKGROUND:To curb rising healthcare expenditures in the U.S.A., the factors underlying this growth must be well understood. OBJECTIVE:We aim to explore how chronic disease prevalence, obesity, and improved disease detection and treatment rates contributed to the growth in health spending in the U.S.A. between 1987 and 2011. METHODS:We use spending decomposition equations to estimate the portion of spending growth attributable to prevalence increases, rising treatment costs, and population growth, respectively. We use two-part models to estimate the portion of prevalence-related spending that is potentially due to obesity. We examine changing diagnosis and treatment rates to assess how much of the growth in spending might be desirable. RESULTS:We find that the share of total healthcare spending associated with the treatment of chronic disease has risen dramatically from 1987-2011. In particular, we estimate that 77.6% of healthcare spending growth is attributable to patients with four or more chronic conditions. We find that rising obesity levels may explain between 11.4 and 23.5% of the increase in healthcare expenditure for several specific chronic conditions. Diagnosis and treatment rates for chronic disease are improving. CONCLUSIONS:Individuals with multiple chronic conditions are disproportionately responsible for rising healthcare expenditure. Much of spending growth associated with rising rates of chronic disease can be linked to rising obesity rates. Though much of the growth in spending is generally considered undesirable, disease detection and treatment rates are also rising, suggesting that at least some of the recent growth in healthcare expenditure may be beneficial. 10.1007/s40258-015-0164-7
    Philosophical determinants of obesity as a disease. Kilov D,Kilov G Obesity reviews : an official journal of the International Association for the Study of Obesity Is obesity a disease? Much ink has been spilled over this debate and for good reasons. The global prevalence of obesity has more than doubled since the 1980s and is now of pandemic proportions. Whether obesity is a disease has consequences for what kind of treatments are appropriate, as well as how we ought to allocate funding and access to healthcare resources. In most cases, there is no dispute over the medical facts, yet disagreement persists. This is because whether obesity is a disease is not determined by medical facts alone; the issue is, in part, conceptual. Science relies on careful argumentation and conceptual analysis as part of its armamentarium. In this review, we will examine the two concepts of disease most often employed in the philosophy of medicine: the naturalistic and constructivist. We will argue that, whichever definition of a disease is used, obesity fits the criteria for disease definition. Those seeking to meet the challenge of managing obesity will, therefore, need to embrace chronic disease models of care suited to addressing the lifelong challenge posed by this disease and its associated complications. 10.1111/obr.12597
    Weighty concerns: the growing prevalence of obesity among older adults. Houston Denise K,Nicklas Barbara J,Zizza Claire A Journal of the American Dietetic Association The prevalence of obesity among older adults has increased during the past 20 years and will affect both medical and social services. Along with an increased risk of cardiovascular disease, diabetes, and several cancers, obesity is associated with increased risk of physical and cognitive disability. However, relatively little attention has been given to the issue of weight management among community-dwelling older adults. Intentional weight loss in obese older adults has not been widely advocated by health care providers due to the uncertainty of whether the benefits outweigh the risks. Limited data in older adults show that intentional weight loss is effective in improving diabetes, cardiovascular risk factors, and physical function. This review describes the changes in body composition associated with aging, the consequences of obesity in older adults, and the effect of intentional weight loss on chronic disease risk factors and physical function. Recommendations for weight loss in obese older adults that minimize the likelihood of adverse effects on muscle mass, bone density, or other aspects of nutritional status are reviewed. Specific recommendations for macronutrient intake, in particular protein, and selected micronutrients, vitamin D and B-12, as well as dietary fiber, and fluid intake as part of a hypocaloric diet and recommendations for physical activity are described. As part of the health professionals team, dietetics practitioners need to be able to guide and manage weight loss treatment options on an individual basis by evaluating the potential benefits against the potential risks in obese older adults. 10.1016/j.jada.2009.08.014
    Addressing Obesity in Aging Patients. Batsis John A,Zagaria Alexandra B The Medical clinics of North America Obesity in older adults affects not only morbidity and mortality but, importantly, quality of life and the risk of institutionalization. Weight loss interventions can effectively lead to improved physical function. Diet-alone interventions can detrimentally affect muscle and bone physiology and, without interventions to affect these elements, can lead to adverse outcomes. Understanding social and nutritional issues facing older adults is of utmost importance to primary care providers. This article will also discuss the insufficient evidence related to pharmacotherapy as well as providing an overview of using physiologic rather than chronologic age for identifying suitable candidates for bariatric surgery. 10.1016/j.mcna.2017.08.007
    MECHANISMS IN ENDOCRINOLOGY: Brown adipose tissue in humans: regulation and metabolic significance. Thuzar Moe,Ho Ken K Y European journal of endocrinology The recent discovery that functional brown adipose tissue (BAT) persists in adult humans has enkindled a renaissance in metabolic research, with a view of harnessing its thermogenic capacity to combat obesity. This review focuses on the advances in the regulation and the metabolic significance of BAT in humans. BAT activity in humans is stimulated by cold exposure and by several factors such as diet and metabolic hormones. BAT function is regulated at two levels: an acute process involving the stimulation of the intrinsic thermogenic activity of brown adipocytes and a chronic process of growth involving the proliferation of pre-existing brown adipocytes or differentiation to brown adipocytes of adipocytes from specific white adipose tissue depots. BAT activity is reduced in the obese, and its stimulation by cold exposure increases insulin sensitivity and reduces body fat. These observations provide strong evidence that BAT plays a significant role in energy balance in humans and has the potential to be harnessed as a therapeutic target for the management of obesity. 10.1530/EJE-15-1217
    Targeting thermogenesis in brown fat and muscle to treat obesity and metabolic disease. Betz Matthias J,Enerbäck Sven Nature reviews. Endocrinology Brown fat is emerging as an interesting and promising target for therapeutic intervention in obesity and metabolic disease. Activation of brown fat in humans is associated with marked improvement in metabolic parameters such as levels of free fatty acids and insulin sensitivity. Skeletal muscle is another important organ for thermogenesis, with the capacity to induce energy-consuming futile cycles. In this Review, we focus on how these two major thermogenic organs - brown fat and muscle - act and cooperate to maintain normal body temperature. Moreover, in the light of disease-relevant mechanisms, we explore the molecular pathways that regulate thermogenesis in brown fat and muscle. Brown adipocytes possess a unique cellular mechanism to convert chemical energy into heat: uncoupling protein 1 (UCP1), which can short-circuit the mitochondrial proton gradient. However, recent research demonstrates the existence of several other energy-expending 'futile' cycles in both adipocytes and muscle, such as creatine and calcium cycling. These mechanisms can complement or even substitute for UCP1-mediated thermogenesis. Moreover, they expand our view of cold-induced thermogenesis from a special feature of brown adipocytes to a more general physiological principle. Finally, we discuss how thermogenic mechanisms can be exploited to expend energy and hence offer new therapeutic opportunities. 10.1038/nrendo.2017.132
    Perivascular Adipose Tissue as a Relevant Fat Depot for Cardiovascular Risk in Obesity. Costa Rafael M,Neves Karla B,Tostes Rita C,Lobato Núbia S Frontiers in physiology Obesity is associated with increased risk of premature death, morbidity, and mortality from several cardiovascular diseases (CVDs), including stroke, coronary heart disease (CHD), myocardial infarction, and congestive heart failure. However, this is not a straightforward relationship. Although several studies have substantiated that obesity confers an independent and additive risk of all-cause and cardiovascular death, there is significant variability in these associations, with some lean individuals developing diseases and others remaining healthy despite severe obesity, the so-called metabolically healthy obese. Part of this variability has been attributed to the heterogeneity in both the distribution of body fat and the intrinsic properties of adipose tissue depots, including developmental origin, adipogenic and proliferative capacity, glucose and lipid metabolism, hormonal control, thermogenic ability, and vascularization. In obesity, these depot-specific differences translate into specific fat distribution patterns, which are closely associated with differential cardiometabolic risks. The adventitial fat layer, also known as perivascular adipose tissue (PVAT), is of major importance. Similar to the visceral adipose tissue, PVAT has a pathophysiological role in CVDs. PVAT influences vascular homeostasis by releasing numerous vasoactive factors, cytokines, and adipokines, which can readily target the underlying smooth muscle cell layers, regulating the vascular tone, distribution of blood flow, as well as angiogenesis, inflammatory processes, and redox status. In this review, we summarize the current knowledge and discuss the role of PVAT within the scope of adipose tissue as a major contributing factor to obesity-associated cardiovascular risk. Relevant clinical studies documenting the relationship between PVAT dysfunction and CVD with a focus on potential mechanisms by which PVAT contributes to obesity-related CVDs are pointed out. 10.3389/fphys.2018.00253
    The pathophysiology of abdominal adipose tissue depots in health and disease. Walker Gillian E,Marzullo Paolo,Ricotti Roberta,Bona Gianni,Prodam Flavia Hormone molecular biology and clinical investigation Obesity is currently the most important contributor to ill health and expenditure worldwide. More alarming is the fact that the pediatric population parallels adults, with obesity closely associated to type 2 diabetes mellitus (T2D), cardiovascular disease, hypertension, non-alcoholic fatty liver disease, vitamin D deficiency (VDD) and certain types of cancer. The observation in the early 1950s that android or truncal adipose tissue (AT) distribution compared to gynoid had a greater association with metabolic dysfunction, in particular T2D and cardiovascular disease risk, led to the hypothesis that obesity-associated complications are not associated with fat mass per se, but the pattern of fat distribution. This concept was further supported by groups of individuals with metabolic dysfunction despite a lean phenotype, and healthy obese people protected from metabolic dysfunction. It is now well recognized that an increase in visceral AT is an independent risk factor for the development of obesity-associated comorbidities with AT depot distribution, their anatomic, cellular and molecular features defining their role. The differences and the plasticity of subcutaneous, visceral and ectopic ATs to store and release fatty acids and to synthesize and secrete adipokines, defines the metabolic outcomes. The present review will examine the phenotypic and pathophysiological differences between the different AT depots, with a particular focus on the abdominal depots and their link to metabolic complications. 10.1515/hmbci-2014-0023
    Adipose tissue heterogeneity: implication of depot differences in adipose tissue for obesity complications. Lee Mi-Jeong,Wu Yuanyuan,Fried Susan K Molecular aspects of medicine Obesity, defined as excess fat mass, increases risks for multiple metabolic diseases, such as type 2 diabetes, cardiovascular disease and several types of cancer. Over and above fat mass per se, the pattern of fat distribution, android or truncal as compared to gynoid or peripheral, has a profound influence on systemic metabolism and hence risk for metabolic diseases. Increases in upper body adipose tissue (visceral and abdominal subcutaneous) confer an independent risk, while the quantity of gluteofemoral adipose tissue is protective. Variations in the capacity of different depots to store and release fatty acids and to produce adipokines are important determinants of fat distribution and its metabolic consequences. Depot differences in cellular composition and physiology, including innervation and blood flow, likely influence their phenotypic properties. A number of lines of evidence also support the idea that adipocytes from different anatomical depots are intrinsically different as a result of genetic or developmental events. In this chapter, we will review the phenotypic characteristics of different adipose depots and mechanisms that link their depot-specific biology to metabolic complications in men and women. 10.1016/j.mam.2012.10.001
    Obesity phenotypes: depot-differences in adipose tissue and their clinical implications. Guglielmi Valeria,Sbraccia Paolo Eating and weight disorders : EWD Obesity, defined as excess fat mass, increases risks for multiple chronic diseases, such as type 2 diabetes, cardiovascular disease, and several types of cancer. Beyond adiposity per se, the pattern of fat distribution, android or truncal as compared to gynoid or peripheral, has a profound influence on systemic metabolism and hence risk for obesity complications. Not only factors as genetics, environment, gender, and age account for the apparent compartmentalization of white adipose tissue (WAT) in the body. Indeed, the heterogeneity among different anatomical depots also appears to stem from their intrinsic diversity, including cellular developmental origin, proliferative capacity, glucose and lipid metabolism, insulin sensitivity, cytokine pattern, thermogenic ability, and vascularization. Under the obese condition, these depot-specific differences translate into specific WAT distribution patterns, giving rise to different cardiometabolic consequences. This review summarizes the clinical and mechanistic evidence for the depot-specific differences and the phenotypic characteristics of different WAT depots that link their depot-specific biology to obesity-specific complications. 10.1007/s40519-017-0467-9
    Molecular mechanism of obesity-induced 'metabolic' tissue remodeling. Tanaka Miyako,Itoh Michiko,Ogawa Yoshihiro,Suganami Takayoshi Journal of diabetes investigation Chronic inflammation is a common molecular basis underlying a variety of chronic diseases. Accumulating evidence has also suggested that chronic inflammation contributes to the pathogenesis of obesity and diabetes, which have been considered as metabolic diseases. For the past several decades, there has been dramatic progress in understanding the underlying mechanism of adipose tissue dysfunction induced by obesity. Tissue remodeling is one of the histological features of chronic inflammation, in which stromal cells dramatically change in number and cell type. Indeed, adipose tissue remodeling is induced by various stromal cells, and results in the impairment of adipose tissue function, such as adipocytokine production and lipid storage, which leads to systemic metabolic disorder. In addition to adipose tissue, the liver is another example of obesity-induced tissue remodeling. In the present review, we discuss how obesity induces interstitial fibrosis in adipose tissue and the liver, particularly focusing on the role of macrophages. 10.1111/jdi.12769
    Challenges to Safe and Effective Pain Management in Patients With Super Obesity: Case Report and Literature Review. Kramer Neha M,Gazelka Halena M,Thompson Virginia H,Batsis John A,Swetz Keith M Journal of pain and symptom management 10.1016/j.jpainsymman.2017.11.005
    Cellular mechanisms underlying obesity-induced arterial stiffness. Aroor Annayya R,Jia Guanghong,Sowers James R American journal of physiology. Regulatory, integrative and comparative physiology Obesity is an emerging pandemic driven by consumption of a diet rich in fat and highly refined carbohydrates (a Western diet) and a sedentary lifestyle in both children and adults. There is mounting evidence that arterial stiffness in obesity is an independent and strong predictor of cardiovascular disease (CVD), cognitive functional decline, and chronic kidney disease. Cardiovascular stiffness is a precursor to atherosclerosis, systolic hypertension, cardiac diastolic dysfunction, and impairment of coronary and cerebral flow. Moreover, premenopausal women lose the CVD protection normally afforded to them in the setting of obesity, insulin resistance, and diabetes, and this loss of CVD protection is inextricably linked to an increased propensity for arterial stiffness. Stiffness of endothelial and vascular smooth muscle cells, extracellular matrix remodeling, perivascular adipose tissue inflammation, and immune cell dysfunction contribute to the development of arterial stiffness in obesity. Enhanced endothelial cortical stiffness decreases endothelial generation of nitric oxide, and increased oxidative stress promotes destruction of nitric oxide. Our research over the past 5 years has underscored an important role of increased aldosterone and vascular mineralocorticoid receptor activation in driving development of cardiovascular stiffness, especially in females consuming a Western diet. In this review the cellular mechanisms of obesity-associated arterial stiffness are highlighted. 10.1152/ajpregu.00235.2016
    Relations of Metabolically Healthy and Unhealthy Obesity to Digital Vascular Function in Three Community-Based Cohorts: A Meta-Analysis. Brant Luisa C C,Wang Na,Ojeda Francisco M,LaValley Michael,Barreto Sandhi M,Benjamin Emelia J,Mitchell Gary F,Vasan Ramachandran S,Palmisano Joseph N,Münzel Thomas,Blankenberg Stefan,Wild Philipp S,Zeller Tanja,Ribeiro Antonio L P,Schnabel Renate B,Hamburg Naomi M Journal of the American Heart Association BACKGROUND:Microvascular dysfunction is a marker of early vascular disease that predicts cardiovascular events. Whether metabolically healthy obese individuals have impaired microvascular function remains unclear. The aim of this study was to evaluate the relation of obesity phenotypes stratified by metabolic status to microvascular function. METHODS AND RESULTS:We meta-analyzed aggregate data from 3 large cohorts (Brazilian Longitudinal Study of Adult Health, the Framingham Heart Study, and the Gutenberg Heart Study; n=16 830 participants, age range 19-90, 51.3% men). Regression slopes between cardiovascular risk factors and microvascular function, measured by peripheral arterial tonometry (PAT), were calculated. Individuals were classified as normal-weight, overweight, or obese by body mass index (BMI) and stratified by healthy or unhealthy metabolic status based on metabolic syndrome using the ATP-III criteria. Male sex, BMI, and metabolic risk factors were associated with higher baseline pulse amplitude and lower PAT ratio. There was stepwise impairment of vascular measures from normal weight to obesity in both metabolic status strata. Metabolically healthy obese individuals had more impaired vascular function than metabolically healthy normal-weight individuals (baseline pulse amplitude 6.12±0.02 versus 5.61±0.01; PAT ratio 0.58±0.01 versus 0.76±0.01, all <0.0001). Metabolically unhealthy obese individuals had more impaired vascular function than metabolically healthy obese individuals (baseline pulse amplitude 6.28±0.01 versus 6.12±0.02; PAT ratio 0.49±0.01 versus 0.58±0.01, all <0.0001). CONCLUSIONS:Metabolically healthy obese individuals have impaired microvascular function, though the degree of impairment is less marked than in metabolically unhealthy obese individuals. Our findings suggest that obesity is detrimental to vascular health irrespective of metabolic status. 10.1161/JAHA.116.004199
    Metabolically healthy obesity and health-related quality of life: A prospective cohort study. Lopez-Garcia E,Guallar-Castillón P,Garcia-Esquinas E,Rodríguez-Artalejo F Clinical nutrition (Edinburgh, Scotland) BACKGROUND:Metabolically healthy obesity (MHO) has been associated with lower risk of diabetes than obesity with cardiometabolic abnormalities (CA). However, the effect of MHO on other health outcomes is unknown. OBJECTIVE:To examine the association of metabolic status across categories of body mass index (BMI) with health-related quality of life (HRQL). METHODS:Prospective cohort with 4397 individuals aged ≥18 years, recruited in 2008-2010 and followed-up to 2012 in Spain. Normal weight was defined as BMI <25, overweight as BMI 25-29.9, and obesity as BMI ≥30 kg/m. Two metabolic statuses were defined: healthy (0-1 CA) and unhealthy (≥2 CA). HRQL was measured with the physical component summary (PCS) and the mental component summary (MCS) of the SF-12 questionnaire. The association of joint categories of BMI and metabolic status at baseline with HRQL at 2012 was examined using linear regression, and adjusted for the main confounders. RESULTS:Compared to healthy normal-weight subjects, the unhealthy normal-weight and the healthy overweight individuals had a similar PCS score; however, the PCS was lower (worse) among those with unhealthy overweight (-1.79; 95% confidence interval [CI]: -2.66 to -0.94), with MHO (-1.45; 95% CI: -2.67 to -0.24) and unhealthy obesity (-1.97; 95% CI: -2.88 to -1.05). Being overweight or obese was not associated with the MCS score regardless of metabolic status. CONCLUSION:Metabolically unhealthy overweight, as well as obesity regardless of metabolic status, showed a worse physical HRQL. These results suggest that both obesity and CA should be addressed to improve HRQL. 10.1016/j.clnu.2016.04.028
    Metabolically healthy and unhealthy weight statuses, health issues and related costs: Findings from the 2013-2015 European Health Examination Survey in Luxembourg. Samouda H,Ruiz-Castell M,Karimi M,Bocquet V,Kuemmerle A,Chioti A,Dadoun F,Stranges S Diabetes & metabolism AIM:To investigate the relationship between metabolically healthy and unhealthy weight statuses and a wide range of related health issues, and healthcare and loss-of-productivity costs. METHODS:A total of 693 men and 729 women, aged 25-64 years, took part in the European Health Examination Survey conducted in Luxembourg between 2013 and 2015. Metabolically unhealthy normal-weight profiles were defined as having two or more cardiometabolic abnormalities (high blood pressure, high fasting glucose or triglycerides, low HDL cholesterol and/or previously diagnosed hypertension or diabetes) in people with normal weight. Metabolically healthy overweight/obesity was defined as having fewer than two of the above-mentioned abnormalities in people with overweight or obesity. For the present report, the participants' anthropometric, clinical, biological, sociodemographic, lifestyle and health-related data were analyzed. RESULTS:Of the participants with normal weight, 20% had a metabolically unhealthy profile, whereas 60% with overweight and 30% with obesity had a metabolically healthy profile. Comparisons between metabolically healthy and unhealthy normal weight, overweight and/or obesity status revealed that participants presented with a metabolically unhealthy profile independently of weight status (P<0.0001). People with a metabolically healthy profile were more likely to perceive their health as good (66%; P<0.0001), and to report no physical pain (64%; P=0.03), no limitations in daily activities (66%; P=0.0008), no difficulties getting in or out of a bed or chair (63%; P=0.02) or dressing and undressing (63%; P=0.003), going shopping (63%; P=0.053) or doing occasional heavy housework (64%; P=0.007); they also displayed fewer gastrointestinal (63%; P=0.02), arthrosis (64%; P=0.001) and sleep apnoea issues (63%; P=0.002) compared with those with a metabolically unhealthy profile. Healthcare- and loss-of-productivity-related costs were higher with a metabolically unhealthy profile, with differences of up to € 3000 (P=0.02). CONCLUSION:The present work has highlighted that, independently of weight status, people may develop a metabolically unhealthy profile associated with several health issues as well as higher healthcare and loss-of-productivity costs. 10.1016/j.diabet.2017.11.007
    Metabolically healthy obesity: the low-hanging fruit in obesity treatment? Stefan Norbert,Häring Hans-Ulrich,Schulze Matthias B The lancet. Diabetes & endocrinology Obesity increases the risk of several other chronic diseases and, because of its epidemic proportions, has become a major public health problem worldwide. Alarmingly, a lower proportion of adults have tried to lose weight during the past decade than during the mid-1980s to 1990s. The first-line treatment option for obesity is lifestyle intervention. Although this approach can decrease fat mass in the short term, these beneficial effects typically do not persist. If a large amount of weight loss is not an easily achievable goal, other goals that might motivate people with obesity to adopt a healthy lifestyle should be considered. In this setting, the concept of metabolically healthy obesity is useful. Accumulating evidence suggests that, although the risk of all-cause mortality and cardiovascular events might be higher in people with metabolically healthy obesity compared with metabolically healthy people of a normal weight, the risk is substantially lower than in individuals with metabolically unhealthy obesity. Therefore, every person with obesity should be motivated to achieve a normal weight in the long term, but more moderate weight loss sufficient for the transition from metabolically unhealthy obesity to metabolically healthy obesity might also lower the risk of adverse outcomes. However, how much weight needs to be lost for this transition to occur is under debate. This transition might be supported by lifestyle factors-such as the Mediterranean diet-that affect cardiovascular risk, independent of body fat. In this Series paper, we summarise available information about the concept of metabolically healthy obesity, highlight gaps in research, and discuss how this concept can be implemented in clinical care. 10.1016/S2213-8587(17)30292-9
    The obesity supine death syndrome (OSDS). Lemyze M,Guiot A,Mallat J,Thevenin D Obesity reviews : an official journal of the International Association for the Study of Obesity The obesity supine death syndrome refers to a catastrophic cascade of cardiorespiratory complications resulting from the supine positioning of a morbidly obese subject which can ultimately lead to death. It was first described in 1977 in two massively obese patients who were forced to lie down for medical procedures. But surprisingly, despite the current worldwide epidemic of obesity, very few cases have been reported yet. It can be assumed that the syndrome is poorly recognized in clinical practice and may participate in the high rate of unexplained death in morbidly obese patients. Based on the previously published cases and on those we met, this review aims at helping clinicians to early detect at-risk patients, to correctly diagnose this dramatic syndrome and to understand the underlying pathophysiology. More importantly, the main objective is to convince the attending clinicians that they have to do everything in their power to prevent obesity supine death syndrome occurrence by maintaining morbidly obese patients in the sitting or upright position whenever possible. When the syndrome unfortunately occurs, the best therapeutic approach is based on the immediate return to sitting position. 10.1111/obr.12655
    Impact of Obesity on Remission and Disease Activity in Rheumatoid Arthritis: A Systematic Review and Meta-Analysis. Liu Yang,Hazlewood Glen S,Kaplan Gilaad G,Eksteen Bertus,Barnabe Cheryl Arthritis care & research OBJECTIVE:To summarize the relationship between obesity and remission in rheumatoid arthritis (RA); secondary objectives were to summarize other measures of treatment response and mortality in RA. METHODS:Medline and Embase searches were performed in March 2016 using relevant MeSH and keyword terms for obesity and RA. Articles were selected if they reported estimates for achieving remission in obese subjects relative to other body mass index (BMI) categories, or changes in composite or individual disease activity measures or patient-reported outcomes during therapy, or mortality rates, in relation to BMI category or on a continuous scale. Remission outcomes were conducive to meta-analysis, and all other outcomes were summarized. RESULTS:A total of 3,368 records were screened; we included 8 reporting remission rates, 9 reporting disease activity measures or patient-reported outcomes, and 3 examining mortality by obesity status or BMI. Obese patients attain remission less frequently than nonobese and/or normal-weight patients. In adjusted models, obese patients demonstrated lower odds of achieving remission (pooled odds ratio [OR] 0.57 [95% confidence interval (95% CI) 0.45, 0.72]) and sustained remission (pooled OR 0.49 [95% CI 0.32, 0.74]) relative to nonobese subjects. Most studies found obese patients to have worse Disease Activity Scores or Disease Activity Scores in 28 joints, tender joint counts, inflammatory markers, patient global evaluation scores, pain scores, and physical function scores during followup, but not worse swollen joint counts. Obesity was not associated with increased mortality. CONCLUSION:Obesity decreases the odds of achieving remission in RA and negatively impacts disease activity and patient-reported outcomes during therapy. Interventions to reduce BMI should be investigated for their ability to improve disease outcomes. 10.1002/acr.22932
    Nutrient excess and autophagic deficiency: explaining metabolic diseases in obesity. van Niekerk Gustav,du Toit André,Loos Ben,Engelbrecht Anna-Mart Metabolism: clinical and experimental Over-nutrition and a sedentary lifestyle are the driving forces behind the development of metabolic diseases. Conversely, caloric restriction and exercise have proven to be the most effective strategies in combating metabolic diseases. Interestingly, exercise and caloric restriction share a common feature: both represent a potent mechanism for upregulating autophagy. Autophagy is rapidly induced by nutrient deprivation, and conversely, inactivated by amino acids as well as growth factors (e.g. insulin). Here, we review evidence demonstrating that autophagy may indeed be attenuated in metabolic tissue such as liver, muscle, and adipose, in the context of obesity. We also highlight the mechanistic basis by which defective autophagy may contribute to the manifestation of metabolic diseases. This includes a compromised ability of the cell to perform quality control on the mitochondrial matrix, since autophagy plays a pivotal role in the degradation of defective mitochondria. Similarly, autophagy also plays an indispensable role in the clearance of protein aggregates and redundant large protein platforms such as inflammasomes. Autophagy might also play a key role in the metabolism of endotoxins, implicating the importance of autophagy in the pathogenesis of metabolic endotoxemia. These observations underpin an unprecedented role of autophagy in the manifestation of obesity-induced metabolic derangement. 10.1016/j.metabol.2017.12.007
    Overweightness, obesity and arterial stiffness in healthy subjects: a systematic review and meta-analysis of literature studies. Li Ping,Wang Lei,Liu Chao Postgraduate medicine OBJECTIVE:The relationship between overweightness, obesity and arterial stiffness remains unclear. We performed a meta-analysis evaluating the impact of obesity/overweightness on arterial stiffness in healthy subjects. METHODS:Literature searches were conducted using databases (eg, MEDLINE, EMBASE) and citations cross-referenced. Studies evaluating the relationship between obesity/overweightness and cfPWV, baPWV, and AIx were systematically searched. A total of 10 studies (1,124 obese/overweight subjects, 1,884 controls) were included. RESULTS:Compared to controls, obese/overweight subjects showed a significantly higher cfPWV (SMD 0.50 m/s; 95%CI 0.15, 0.86; P = 0.005), baPWV (SMD 0.41 m/s; 95% CI 0.08, 0.74; P = 0.014), and AIx (SMD 1.02;95%CI 0.16, 1.87; P < 0.0001). When analyzing 'high quality' studies, the difference in arterial stiffness among obese/overweight subjects and controls remain (SMD 0.73 m/s; 95%CI 0.16, 1.30; P = 0.013). CONCLUSION:Arterial stiffness, a recognized marker of cardio vascular risk, is increased in obese/overweight subjects without overt cardiovascular diseases. 10.1080/00325481.2017.1268903
    Key factors involved in obesity development. Wang Zhiyou,Yuan Daixiu,Duan Yehui,Li Shujuan,Hou Shengzhen Eating and weight disorders : EWD Obesity has been considered to be a chronic disease that requires medical prevention and treatment. Intriguingly, many factors, including adipose tissue dysfunction, mitochondrial dysfunction, alterations in the muscle fiber phenotype and in the gut microbiota composition, have been identified to be involved in the development of obesity and its associated metabolic disorders (in particular type 2 diabetes mellitus). In this narrative review, we will discuss our current understanding of the relationships of these factors and obesity development, and provide a summary of potential treatments to manage obesity. Level of Evidence Level V, narrative review. 10.1007/s40519-017-0428-3
    Early Life Origins of Obesity and Related Complications. Singhal Atul Indian journal of pediatrics The idea that nutrition in early life (such as before conception, during pregnancy and in infancy) can influence, or programme, long-term health, known as the 'Developmental Origins of Health and Disease Hypothesis', has generated great scientific interest. This concept is particularly relevant for the development of obesity and its complications, arguably the most important public health issue of the twenty-first century worldwide. The concept is strongly supported by evidence from animal studies, both observational and experimental (randomised) studies in humans, and is highly relevant for population health in both low-income and high-incomes countries. For instance, optimising nutrition in pregnancy (both in terms of under-nutrition and over-nutrition) and preventing too fast infant weight gain have been shown to reduce the risk of future obesity. Proposed mechanisms have included effects of early nutrition on the epigenome, hormones such as insulin, and regulation of appetite, that effect long-term risk of obesity. Although further data from experimental studies is required to support a causal link between early nutrition and future adiposity, the developmental origins hypothesis is already changing health policy and practice globally. The present review considers the evidence for the developmental origins of obesity, the mechanisms involved, and the implications for public health. 10.1007/s12098-017-2554-3
    Evidence Supporting the Existence of a Distinct Obese Phenotype of Heart Failure With Preserved Ejection Fraction. Obokata Masaru,Reddy Yogesh N V,Pislaru Sorin V,Melenovsky Vojtech,Borlaug Barry A Circulation BACKGROUND:Heart failure (HF) with preserved ejection fraction (HFpEF) is a heterogeneous syndrome. Phenotyping patients into pathophysiologically homogeneous groups may enable better targeting of treatment. Obesity is common in HFpEF and has many cardiovascular effects, suggesting that it may be a viable candidate for phenotyping. We compared cardiovascular structure, function, and reserve capacity in subjects with obese HFpEF, those with nonobese HFpEF, and control subjects. METHODS:Subjects with obese HFpEF (body mass index ≥35 kg/m; n=99), nonobese HFpEF (body mass index <30 kg/m; n=96), and nonobese control subjects free of HF (n=71) underwent detailed clinical assessment, echocardiography, and invasive hemodynamic exercise testing. RESULTS:Compared with both subjects with nonobese HFpEF and control subjects, subjects with obese HFpEF displayed increased plasma volume (3907 mL [3563-4333 mL] versus 2772 mL [2555-3133 mL], and 2680 mL [2380-3006 mL]; <0.0001), more concentric left ventricular remodeling, greater right ventricular dilatation (base, 34±7 versus 31±6 and 30±6 mm, =0.0005; length, 66±7 versus 61±7 and 61±7 mm, <0.0001), more right ventricular dysfunction, increased epicardial fat thickness (10±2 versus 7±2 and 6±2 mm; <0.0001), and greater total epicardial heart volume (945 mL [831-1105 mL] versus 797 mL [643-979 mL] and 632 mL [517-768 mL]; <0.0001), despite lower N-terminal pro-B-type natriuretic peptide levels. Pulmonary capillary wedge pressure was correlated with body mass and plasma volume in obese HFpEF (=0.22 and 0.27, both <0.05) but not in nonobese HFpEF (≥0.3). The increase in heart volumes in obese HFpEF was associated with greater pericardial restraint and heightened ventricular interdependence, reflected by increased ratio of right- to left-sided heart filling pressures (0.64±0.17 versus 0.56±0.19 and 0.53±0.20; =0.0004), higher pulmonary venous pressure relative to left ventricular transmural pressure, and greater left ventricular eccentricity index (1.10±0.19 versus 0.99±0.06 and 0.97±0.12; <0.0001). Interdependence was enhanced as pulmonary artery pressure load increased ( for interaction <0.05). Compared with those with nonobese HFpEF and control subjects, obese patients with HFpEF displayed worse exercise capacity (peak oxygen consumption, 7.7±2.3 versus 10.0±3.4 and12.9±4.0 mL/min·kg; <0.0001), higher biventricular filling pressures with exercise, and depressed pulmonary artery vasodilator reserve. CONCLUSIONS:Obesity-related HFpEF is a genuine form of cardiac failure and a clinically relevant phenotype that may require specific treatments. 10.1161/CIRCULATIONAHA.116.026807
    Obesity and heart failure with preserved ejection fraction: A growing problem. Prenner Stuart B,Mather Paul J Trends in cardiovascular medicine Heart Failure with Preserved Ejection Fraction (HFpEF) is increasing in prevalence due to the aging of the United States population as well as the current obesity epidemic. While obesity is very common in patients with HFpEF, obesity may represent a specific phenotype of HFpEF characterized by unique hemodynamics and structural abnormalities. Obesity induces a systemic inflammatory response that may contribute to myocardial fibrosis and endothelial dysfunction. The most obese patients continue to be excluded from HFpEF clinical trials, and thus ongoing research is needed to determine the role of pharmacologic and interventional approaches in this growing population. 10.1016/j.tcm.2017.12.003
    From the BMI paradox to the obesity paradox: the obesity-mortality association in coronary heart disease. Antonopoulos A S,Oikonomou E K,Antoniades C,Tousoulis D Obesity reviews : an official journal of the International Association for the Study of Obesity Despite a strong association between body weight and mortality in the general population, clinical evidence suggests better clinical outcome of overweight or obese individuals with established coronary heart disease. This finding has been termed the 'obesity paradox', but its existence remains a point of debate, because it is mostly observed when body mass index (BMI) is used to define obesity. Inherent limitations of BMI as an index of adiposity, as well as methodological biases and the presence of confounding factors, may account for the observed findings of clinical studies. In this review, our aim is to present the data that support the presence of a BMI paradox in coronary heart disease and then explore whether next to a BMI paradox a true obesity paradox exists as well. We conclude by attempting to link the obesity paradox notion to available translational research data supporting a 'healthy', protective adipose tissue phenotype. © 2016 World Obesity. 10.1111/obr.12440
    Time to redefine body mass index categories in chronic diseases? Spotlight on obesity paradox. Egom Emmanuel E,Pharithi Rebabonye B,Shiwani Haaris A,Khan Barkat,Kruzliak Peter,El-Hiani Yassine,Maher Vincent International journal of food sciences and nutrition Obesity is a complex condition classically characterised by excessive body fat accumulation and represents one of the most important public health problems worldwide. Although several epidemiological studies have shown that elevated BMI is associated with higher morbidity, and with increased rate of death from all causes and from cardiovascular disease, accumulating evidence suggests that being overweight or obese may be protective (the so-called obesity paradox), at least in chronic diseases. These observations, not only question the validity of the BMI system, but also raise the intriguing question of whether we should redefine what the normal range of BMI is in individuals suffering from a chronic disease. In the present article, we review the available information on the association between elevated BMI and increased morbidity and mortality including obesity-related paradoxes, explore key aspects of the role and limitations of BMI as a measure of increased adiposity and outline potential solutions to address the current controversies regarding the impact of obesity on human health. 10.1080/09637486.2017.1389859
    Inverse relationship between body mass index and mortality in older nursing home residents: a meta-analysis of 19,538 elderly subjects. Veronese N,Cereda E,Solmi M,Fowler S A,Manzato E,Maggi S,Manu P,Abe E,Hayashi K,Allard J P,Arendt B M,Beck A,Chan M,Audrey Y J P,Lin W-Y,Hsu H-S,Lin C-C,Diekmann R,Kimyagarov S,Miller M,Cameron I D,Pitkälä K H,Lee J,Woo J,Nakamura K,Smiley D,Umpierrez G,Rondanelli M,Sund-Levander M,Valentini L,Schindler K,Törmä J,Volpato S,Zuliani G,Wong M,Lok K,Kane J M,Sergi G,Correll C U Obesity reviews : an official journal of the International Association for the Study of Obesity Body mass index (BMI) and mortality in old adults from the general population have been related in a U-shaped or J-shaped curve. However, limited information is available for elderly nursing home populations, particularly about specific cause of death. A systematic PubMed/EMBASE/CINAHL/SCOPUS search until 31 May 2014 without language restrictions was conducted. As no published study reported mortality in standard BMI groups (<18.5, 18.5-24.9, 25-29.9, ≥30 kg/m(2)), the most adjusted hazard ratios (HRs) according to a pre-defined list of covariates were obtained from authors and pooled by random-effect model across each BMI category. Out of 342 hits, 20 studies including 19,538 older nursing home residents with 5,223 deaths during a median of 2 years of follow-up were meta-analysed. Compared with normal weight, all-cause mortality HRs were 1.41 (95% CI = 1.26-1.58) for underweight, 0.85 (95% CI = 0.73-0.99) for overweight and 0.74 (95% CI = 0.57-0.96) for obesity. Underweight was a risk factor for higher mortality caused by infections (HR = 1.65 [95% CI = 1.13-2.40]). RR results corroborated primary HR results, with additionally lower infection-related mortality in overweight and obese than in normal-weight individuals. Like in the general population, underweight is a risk factor for mortality in old nursing home residents. However, uniquely, not only overweight but also obesity is protective, which has relevant nutritional goal implications in this population/setting. 10.1111/obr.12309
    Association of all-cause mortality with overweight and obesity using standard body mass index categories: a systematic review and meta-analysis. Flegal Katherine M,Kit Brian K,Orpana Heather,Graubard Barry I JAMA IMPORTANCE:Estimates of the relative mortality risks associated with normal weight, overweight, and obesity may help to inform decision making in the clinical setting. OBJECTIVE:To perform a systematic review of reported hazard ratios (HRs) of all-cause mortality for overweight and obesity relative to normal weight in the general population. DATA SOURCES:PubMed and EMBASE electronic databases were searched through September 30, 2012, without language restrictions. STUDY SELECTION:Articles that reported HRs for all-cause mortality using standard body mass index (BMI) categories from prospective studies of general populations of adults were selected by consensus among multiple reviewers. Studies were excluded that used nonstandard categories or that were limited to adolescents or to those with specific medical conditions or to those undergoing specific procedures. PubMed searches yielded 7034 articles, of which 141 (2.0%) were eligible. An EMBASE search yielded 2 additional articles. After eliminating overlap, 97 studies were retained for analysis, providing a combined sample size of more than 2.88 million individuals and more than 270,000 deaths. DATA EXTRACTION:Data were extracted by 1 reviewer and then reviewed by 3 independent reviewers. We selected the most complex model available for the full sample and used a variety of sensitivity analyses to address issues of possible overadjustment (adjusted for factors in causal pathway) or underadjustment (not adjusted for at least age, sex, and smoking). RESULTS:Random-effects summary all-cause mortality HRs for overweight (BMI of 25-<30), obesity (BMI of ≥30), grade 1 obesity (BMI of 30-<35), and grades 2 and 3 obesity (BMI of ≥35) were calculated relative to normal weight (BMI of 18.5-<25). The summary HRs were 0.94 (95% CI, 0.91-0.96) for overweight, 1.18 (95% CI, 1.12-1.25) for obesity (all grades combined), 0.95 (95% CI, 0.88-1.01) for grade 1 obesity, and 1.29 (95% CI, 1.18-1.41) for grades 2 and 3 obesity. These findings persisted when limited to studies with measured weight and height that were considered to be adequately adjusted. The HRs tended to be higher when weight and height were self-reported rather than measured. CONCLUSIONS AND RELEVANCE:Relative to normal weight, both obesity (all grades) and grades 2 and 3 obesity were associated with significantly higher all-cause mortality. Grade 1 obesity overall was not associated with higher mortality, and overweight was associated with significantly lower all-cause mortality. The use of predefined standard BMI groupings can facilitate between-study comparisons. 10.1001/jama.2012.113905
    Impact of obesity on mortality in patients with diabetes: Meta-analysis of 20 studies including 250,016 patients. Gao Fei,Wang Zhi Jian,Shen Hua,Yang Shi Wei,Nie Bin,Zhou Yu Jie Journal of diabetes investigation AIMS/INTRODUCTION:The impact of body mass index on mortality among patients with diabetes remains controversial. Therefore, we carried out a meta-analysis of pertinent studies. MATERIALS AND METHODS:We searched OVID/MEDLINE, EMBASE and Cochrane databases for all reported studies, which investigated the relationship between body mass index and mortality in patients with diabetes. Summary estimates of hazard ratios (HRs) were obtained with a random effects model. Univariate meta-regressions were carried out. RESULTS:A total of 20 studies including 250,016 patients with diabetes were identified. The results of the present study showed a significantly reduced risk of all-cause mortality in overweight patients (HR 0.82, 95% CI: 0.74-0.91, P < 0.0001, and I = 91.6%) as compared with normal weight patients. The survival benefits of obesity were only observed in the elderly patients (HR 0.69, 95% CI: 0.63-0.75, P < 0.0001, and I = 50.4%), but not in the younger patients (HR 1.01, 95% CI: 0.84-1.20, P = 0.96, I = 80.1%). Furthermore, the beneficial prognostic impacts on overweight (coefficient = 0.030, P = 0.041) and obesity (coefficient = 0.032, P = 0.010) were attenuated with clinical follow-up duration. CONCLUSIONS:The present meta-analysis showed a significantly lower risk of all-cause mortality in overweight patients with diabetes compared with normal weight patients. However, the survival benefits of obesity were only observed among the elderly patients. 10.1111/jdi.12677
    Adipocyte dedifferentiation in health and diseases. Song Tongxing,Kuang Shihuan Clinical science (London, England : 1979) Adipose tissues collectively as an endocrine organ and energy storage are crucial for systemic metabolic homeostasis. The major cell type in the adipose tissue, the adipocytes or fat cells, are remarkably plastic and can increase or decrease their size and number to adapt to changes in systemic or local metabolism. Changes in adipocyte size occur through hypertrophy or atrophy, and changes in cell numbers mainly involve de novo generation of new cells or death of existing cells. Recently, dedifferentiation, whereby a mature adipocyte is reverted to an undifferentiated progenitor-like status, has been reported as a mechanism underlying adipocyte plasticity. Dedifferentiation of mature adipocytes has been observed under both physiological and pathological conditions. This review covers several aspects of adipocyte dedifferentiation, its relevance to adipose tissue function, molecular pathways that drive dedifferentiation, and the potential of therapeutic targeting adipocyte dedifferentiation in human health and metabolic diseases. 10.1042/CS20190128
    Metabolically healthy obesity and risk of incident type 2 diabetes: a meta-analysis of prospective cohort studies. Bell J A,Kivimaki M,Hamer M Obesity reviews : an official journal of the International Association for the Study of Obesity The risk of type 2 diabetes among obese adults who are metabolically healthy has not been established. We systematically searched Medline (1946-August 2013) and Embase (1947-August 2013) for prospective studies of type 2 diabetes incidence (defined by blood glucose levels or self-report) among metabolically healthy obese adults (defined by body mass index [BMI] and normal cardiometabolic clustering, insulin profile or risk score) aged ≥18 years at baseline. We supplemented the analysis with an original effect estimate from the English Longitudinal Study of Ageing (ELSA), with metabolically healthy obesity defined as BMI ≥ 30 kg m(-2) and <2 of hypertension, impaired glycaemic control, systemic inflammation, adverse high-density lipoprotein cholesterol and adverse triglycerides. Estimates from seven published studies and ELSA were pooled using random effects meta-analyses (1,770 healthy obese participants; 98 type 2 diabetes cases). The pooled adjusted relative risk (RR) for incident type 2 diabetes was 4.03 (95% confidence interval = 2.66-6.09) in healthy obese adults and 8.93 (6.86-11.62) in unhealthy obese compared with healthy normal-weight adults. Although there was between-study heterogeneity in the size of effects (I(2)  = 49.8%; P = 0.03), RR for healthy obesity exceeded one in every study, indicating a consistently increased risk across study populations. Metabolically healthy obese adults show a substantially increased risk of developing type 2 diabetes compared with metabolically healthy normal-weight adults. Prospective evidence does not indicate that healthy obesity is a harmless condition. 10.1111/obr.12157
    Transition from metabolic healthy to unhealthy phenotypes and association with cardiovascular disease risk across BMI categories in 90 257 women (the Nurses' Health Study): 30 year follow-up from a prospective cohort study. Eckel Nathalie,Li Yanping,Kuxhaus Olga,Stefan Norbert,Hu Frank B,Schulze Matthias B The lancet. Diabetes & endocrinology BACKGROUND:Cardiovascular disease risk among individuals across different categories of BMI might depend on their metabolic health. It remains unclear to what extent metabolic health status changes over time and whether this affects cardiovascular disease risk. In this study, we aimed to examine the association between metabolic health and its change over time and cardiovascular disease risk across BMI categories. METHODS:Between June and December, 1976, 121 701 female nurses were recruited to the Nurses' Health Study (NHS) of whom 103 298 returned a questionnaire in 1980 used as baseline in this study. After excluding women with a history of cardiovascular disease or cancer, with missing body weight and with underweight. 90 257 women were followed-up from 1980 to 2010 for incident cardiovascular disease. Participants were cross-classified by BMI categories, metabolic health (defined by absence of diabetes, hypertension and hypercholesterolaemia), and change in metabolic health status during follow-up. The cardiovascular component of the NHS is registered with ClinicalTrials.gov, number NCT00005152. FINDINGS:During 2 127  391 person-years of follow-up with a median follow-up of 24 years, we documented 6306 cases of cardiovascular disease including 3304 myocardial infarction cases and 3080 strokes. Cardiovascular disease risk of women with metabolically healthy obesity was increased compared with women with metabolically healthy normal weight (HR 1·39, 95% CI 1·15-1·68), but risk was considerably higher in women with metabolically unhealthy normal weight (2·43, 2·19-2·68), overweight (2·61, 2·36-2·89) and obesity (3·15, 2·83-3·50). The majority of metabolically healthy women converted to unhealthy phenotypes (2555 [84%] of 3027 women with obesity, 22 215 [68%] of 32 882 women with normal-weight after 20 years). Women who maintained metabolically healthy obesity during follow-up were still at a higher cardiovascular disease risk compared with women with stable healthy normal weight (HR 1·57, 1·03-2·38), yet this risk was lower than for initially metabolically healthy women who converted to an unhealthy phenotype (normal-weight 1·90, 1·66-2·17 vs obesity 2·74, 2·30-3·27). Particularly incident diabetes and hypertension increased the risk among women with initial metabolic health. INTERPRETATION:Even when metabolic health is maintained during long periods of time, obesity remains a risk factor for cardiovascular disease. However, risks are highest for metabolically unhealthy women across all BMI categories. A large proportion of metabolically healthy women converted to an unhealthy phenotype over time across all BMI categories, which is associated with an increased cardiovascular disease risk. FUNDING:US National Institutes of Health, German Federal Ministry of Education and Research. 10.1016/S2213-8587(18)30137-2
    Metabolically healthy general and abdominal obesity are associated with increased risk of hypertension. Zhao Yang,Qin Pei,Sun Haohang,Liu Yu,Liu Dechen,Zhou Qionggui,Guo Chunmei,Li Quanman,Tian Gang,Wu Xiaoyan,Hu Dongsheng,Sun Xizhuo,Zhang Ming The British journal of nutrition Metabolically healthy obesity refers to a subset of obese people with a normal metabolic profile. We aimed to explore the association between metabolically healthy and obesity status and risk of hypertension among Chinese adults from The Rural Chinese Cohort Study. This prospective cohort study enrolled 9137 Chinese adults without hypertension, type 2 diabetes or treatment for lipid abnormality at baseline (2007-2008) and followed up during 2013-2014. Modified Poisson regression models were used to examine the risk of hypertension by different metabolically healthy and obesity status, estimating relative risks (RR) and 95 % CI. During 6 years of follow-up, we identified 1734 new hypertension cases (721 men). After adjusting for age, sex, smoking and other confounding factors, risk of hypertension was increased with metabolically healthy general obesity (MHGO) defined by BMI (RR 1·75, 95 % CI 1·02, 3·00) and metabolically healthy abdominal obesity (MHAO) defined by waist circumference (RR 1·51, 95 % CI 1·12, 2·04) as compared with metabolically healthy non-obesity. The associations between metabolically healthy and obesity status and hypertension outcome were consistent after stratifying by sex, age, smoking, alcohol drinking and physical activity. Both MHGO and MHAO were associated with increased risk of hypertension. Obesity control programmes should be implemented to prevent or delay the development of hypertension in rural China. 10.1017/S0007114519003143
    When to Eat: The Importance of Eating Patterns in Health and Disease. Manoogian Emily N C,Chaix Amandine,Panda Satchidananda Journal of biological rhythms 10.1177/0748730419892105
    Strong association between metabolically-abnormal obesity and gallstone disease in adults under 50 years. Su Pei-Yuan,Hsu Yu-Chun,Cheng Yu-Fang,Kor Chew-Teng,Su Wei-Wen BMC gastroenterology BACKGROUND:Age, obesity, and metabolic syndrome are known risk factors for gallstones; however, the combined impact of these different risk factors on gallstone formation has not yet been examined. METHODS:This retrospective, cross-sectional study involved 3190 participants, including 207 participants (6.5%) with gallstones and 986 (30.9%) with metabolic syndrome. Participants were divided into four phenotypes according to metabolic syndrome and obesity status: 1378 participants were metabolically healthy and non-obese (MHNO); 826 were metabolically healthy but obese (MHO); 185 were metabolically abnormal but not obese (MANO); and 801 participants were metabolically abnormal and obese (MAO). RESULTS:The MAO and MANO phenotypes had more gallstones than the MHO and MHNO phenotypes, regardless of age (< 50 or ≥ 50 years old). Multivariate analyses showed that phenotype was an independent risk factor for gallstones in participants < 50 years old (odds ratio (OR) = 1.73, 95% confidence interval (CI) = 1.32-2.28). Younger participants also had a higher risk of gallstones in the MAO (OR = 5.41, 95% CI = 2.31-12.66), MANO (OR = 3.18, 95% CI = 0.86-11.75), and MHO (OR = 2.17, 95% CI = 0.90-5.22) phenotypes than the MHNO phenotype. CONCLUSIONS:Our retrospective results demonstrate an increased association of gallstones in younger people (< 50 years old) with metabolic syndrome and obesity. 10.1186/s12876-019-1032-y
    Waist-to-height ratio is a better screening tool than waist circumference and BMI for adult cardiometabolic risk factors: systematic review and meta-analysis. Ashwell M,Gunn P,Gibson S Obesity reviews : an official journal of the International Association for the Study of Obesity Our aim was to differentiate the screening potential of waist-to-height ratio (WHtR) and waist circumference (WC) for adult cardiometabolic risk in people of different nationalities and to compare both with body mass index (BMI). We undertook a systematic review and meta-analysis of studies that used receiver operating characteristics (ROC) curves for assessing the discriminatory power of anthropometric indices in distinguishing adults with hypertension, type-2 diabetes, dyslipidaemia, metabolic syndrome and general cardiovascular outcomes (CVD). Thirty one papers met the inclusion criteria. Using data on all outcomes, averaged within study group, WHtR had significantly greater discriminatory power compared with BMI. Compared with BMI, WC improved discrimination of adverse outcomes by 3% (P < 0.05) and WHtR improved discrimination by 4-5% over BMI (P < 0.01). Most importantly, statistical analysis of the within-study difference in AUC showed WHtR to be significantly better than WC for diabetes, hypertension, CVD and all outcomes (P < 0.005) in men and women. For the first time, robust statistical evidence from studies involving more than 300 000 adults in several ethnic groups, shows the superiority of WHtR over WC and BMI for detecting cardiometabolic risk factors in both sexes. Waist-to-height ratio should therefore be considered as a screening tool. 10.1111/j.1467-789X.2011.00952.x
    Association between anthropometric indicators of obesity and cardiovascular risk factors among adults in Shanghai, China. Zhang Yue,Gu Yi'an,Wang Na,Zhao Qi,Ng Nawi,Wang Ruiping,Zhou Xiaoyan,Jiang Yonggen,Wang Weibing,Zhao Genming BMC public health BACKGROUND:To determine the optimal cut-off values and evaluate the associations of body mass index (BMI), waist circumference (WC) and waist-height ratio (WHtR) with cardiovascular disease (CVD) risk factors. METHODS:A large-scale cross-sectional survey was conducted among 35,256 adults aged 20-74 years in Shanghai between June 2016 and December 2017. Receiver operating characteristic (ROC) analyses were conducted to assess the optimal cut-off anthropometric indices of CVD risk factors including hypertension, diabetes, dyslipidemia and hyperuricemia. Multivariate Logistic regression models were preformed to evaluate the odds ratio of CVD risk factors. RESULTS:The area under the curve (AUC) of WHtR was significantly greater than that of BMI or WC in the prediction of hypertension and diabetes, and AUCs were higher in women than men. The optimal cut-off values of WHtR were approximately 0.51 in both sexes, while the cut-off values of BMI and WC were higher for men compared with women. The optimal cutoff values of BMI and WC varied greatly across different age groups, but the difference in WHtR was relatively slight. Among women, the optimal threshold of anthropometric indices appeared to increase with age for hypertension and diabetes. The odds ratio between anthropometric indices and CVD risk factors were attenuated with age. WHtR had the greatest odds ratio for CVD risk factors among adults under 60 years old except for women with hypertension, while among 60-74 years, BMI yielded the greatest odds ratio in terms of all CVD outcomes except for women with diabetes. CONCLUSIONS:WHtR had the best performance for discriminating hypertension and diabetes and potentially be served as a standard screening tool in public health. The associations between three anthropometric indices and CVD risk factors differed by sex and decreased with age. These findings indicated a need to develop age- and gender-specific difference and make effective strategies for primary prevention of CVDs. 10.1186/s12889-019-7366-0
    Anthropometric variables as cardiovascular risk predictors in a cohort of adult subjects with Turner syndrome. Álvarez-Nava Francisco,Racines Marcia,Witt Julia,Guarderas Jéssica,Estévez María,Lanes Roberto Diabetes, metabolic syndrome and obesity : targets and therapy Background and purpose:Excessive adiposity is associated with cardiometabolic complications in Turner syndrome (TS) subjects. Reference data for predictive anthropometric indices of overweight/obesity and metabolic syndrome (MetS) are lacking for subjects with TS. The purpose of this study was to identify the best anthropometric predictor of cardiometabolic risk in a Latin-American cohort of TS subjects. Patients and methods:This was a cross-sectional correlational study conducted in adult TS subjects (n=88) over the past seven years. Anthropometric parameters, body composition and biochemical variables were evaluated in a study and in a reference (n=57) group. Overweight/obesity and MetS were diagnosed using international consensus. The area under the ROC curve (AUC-ROC) was then used to determine the value of each anthropometric variable in predicting MetS or overweight/obesity. Results:The prevalence of MetS and overweight/obesity in TS subjects was 40% and 48%, respectively. All anthropometric and cardiometabolic variables were significantly increased in TS subjects when compared to the reference group, except for body mass index (BMI) and HDL-c. To detect MetS and overweight/obesity, waist to height ratio (WHtR) was found to have a higher correlation with cardiometabolic variables (TC, LDL-c, HDL-c levels and the LDL-c/HDL-c ratio), and to have a higher AUC-ROC and odds ratio than BMI, waist circumference (WC) and the waist to hip ratio (WHR). Conclusion:The prevalence of MetS and overweight/obesity is elevated in TS subjects. WHtR was the most useful variable in predicting the presence of MetS and overweight and obesity in this TS cohort. A combination of WHtR with BMI or with WC could have the best clinical utility in identifying adult TS subjects with overweight/obesity and MetS, respectively. 10.2147/DMSO.S214787
    New obesity classification criteria as a tool for bariatric surgery indication. De Lorenzo Antonino,Soldati Laura,Sarlo Francesca,Calvani Menotti,Di Lorenzo Nicola,Di Renzo Laura World journal of gastroenterology Obesity plays relevant pathophysiological role in the development of health problems, arising as result of complex interaction of genetic, nutritional, and metabolic factors. Due to the role of adipose tissue in lipid and glucose metabolism, and low grade inflammation, it is necessary to classify obesity on the basis of body fat composition and distribution, rather than the simply increase of body weight, and the Body Mass Index. The new term of adiposopathy (''sick fat'') clearly defines the pathogenic role of adipose tissue. Four phenotypes of obese individuals have been described: (1) normal weight obese (NWO); (2) metabolically obese normal weight; (3) metabolically healthy obese; and (4) metabolically unhealthy obese or "at risk" obese. Moreover, sarcopenic obesity has been related to all the phenotypes. The category of normal weight lean, represented by metabolically healthy normal weight has been classified to distinguish from NWO. It is crucial to recommend a bariatric surgery taking into account adiposopathy and sick fat that occurs with the expansion of fat mass, changing the inflammatory and metabolic profile of the patient. Body fat percentage and genetic polymorphism have to be evaluated to personalize the best bariatric surgery intervention. 10.3748/wjg.v22.i2.681
    Obesity: A preventable, treatable, but relapsing disease. De Lorenzo Antonio,Romano Lorenzo,Di Renzo Laura,Di Lorenzo Nicola,Cenname Giuseppe,Gualtieri Paola Nutrition (Burbank, Los Angeles County, Calif.) In 2013, the American Medical Association recognized obesity as a disease, of growing scientific, social, and political interest. In 2016 in the United States, prevalence rates of preobesity and obesity exceeded 60%. In Italy, these rates exceeded 40%. Total costs related to excess weight reached 9.3% of the U.S. gross domestic product, whereas in Italy the total annual cost of diabetes alone was estimated at 20.3 billion euros/y. The expansion of adipose tissue and visceral fat causes compression, joint stress, metabolic disorders, organ dysfunction, and increased mortality. The increase in peripheral and central fat mass is a chronic and potentially reversible process with appropriate diagnosis and treatment. Conversely, fattening can turn into a chronic relapsing form, complicated by comorbidities and cardiovascular events. The increased risk for mortality and morbidity also can affect metabolically healthy obese individuals, if the condition is underestimated, with disease progression. Due to its inaccuracy, body mass index must be replaced with body composition for the diagnosis of obesity. The chances of obesity reversibility are closely linked to improving the diagnosis and to timely nutritional interventions. Generalization and stigma hinder the treatment of obese individuals. The recognition of obesity as a disease and institutional interest can shift the focus onto obesity and not on the obese, with improvements in adherence to prevention plans. Anthropogenic factors and gut microbiota can influence human behavior and food choice, such as food addiction. Obesity has all the criteria to be recognized as a disease. Proper clinical management will lead to cost and complications savings, such as in diabetes. The aim of this review was to discuss in detail the criteria for defining primary obesity as a disease in a step-by-step manner. 10.1016/j.nut.2019.110615
    Sarcopenic Obesity: Time to Meet the Challenge. Barazzoni Rocco,Bischoff Stephan,Boirie Yves,Busetto Luca,Cederholm Tommy,Dicker Dror,Toplak Hermann,Van Gossum Andre,Yumuk Volkan,Vettor Roberto Obesity facts The prevalence of overweight and obesity has reached epidemic proportions worldwide due to increasingly pervasive obesogenic lifestyle changes. Obesity poses unprecedented individual, social, and multidisciplinary medical challenges by increasing the risk for metabolic diseases, chronic organ failures, and cancer as well as complication rates in the presence of acute disease conditions. Whereas reducing excess adiposity remains the fundamental pathogenic treatment for obese individuals, complex metabolic and lifestyle abnormalities as well as weight reduction therapies per se may also compromise the ability to preserve muscle function and mass, especially when chronic disease co-exists with obesity. Emerging evidence indicates that low muscle mass and quality have a strong negative prognostic impact in obese individuals and may lead to frailty, disability, and increased morbidity and mortality. Awareness of the importance of skeletal muscle maintenance in obesity is however low among clinicians and scientists. The term 'sarcopenic obesity' has been proposed to identify obesity with low skeletal muscle function and mass, but its utilization is largely limited to the aging patient population, and consensus on its definition and diagnostic criteria remains insufficient. Knowledge on prevalence of sarcopenic obesity in various clinical conditions and patient subgroups, on its clinical impacts in patient risk stratification, and on effective prevention and treatment strategies remain therefore dramatically inadequate. In particular, optimal dietary options and medical nutritional support strategies to preserve muscle mass in obese individuals remain largely undefined. The European Society for Clinical Nutrition and Metabolism (ESPEN) and the European Association for the Study of Obesity (EASO) recognize and indicate obesity with altered body composition due to low skeletal muscle function and mass (sarcopenic obesity) as a scientific and clinical priority for researchers and clinicians. ESPEN and EASO therefore call for coordinated action aimed at reaching consensus on its definition, diagnostic criteria, and optimal treatment with particular regard to nutritional therapy. We are convinced that achievement of these goals has a strong potential to reduce the burden of morbidity and mortality in the rapidly increasing obese patient population. 10.1159/000490361
    Sarcopenic obesity: Time to meet the challenge. Barazzoni Rocco,Bischoff Stephan C,Boirie Yves,Busetto Luca,Cederholm Tommy,Dicker Dror,Toplak Hermann,Van Gossum Andre,Yumuk Volkan,Vettor Roberto Clinical nutrition (Edinburgh, Scotland) The prevalence of overweight and obesity has reached epidemic proportions worldwide due to increasingly pervasive obesogenic lifestyle changes. Obesity poses unprecedented individual, social and multi-disciplinary medical challenges by increasing the risk for metabolic diseases, chronic organ failures and cancer, as well as complication rates in the presence of acute disease conditions. Whereas reducing excess adiposity remains the fundamental pathogenetic treatment for obese individuals, complex metabolic and lifestyle abnormalities as well as weight-reduction therapies per se may also compromise the ability to preserve muscle function and mass, especially when chronic disease co-exists with obesity. Emerging evidence indicates that low muscle mass and quality have a strong negative prognostic impact in obese individuals and may lead to frailty, disability and increased morbidity and mortality. Awareness of the importance of skeletal muscle maintenance in obesity is however low among clinicians and scientists. The term "sarcopenic obesity" has been proposed to identify obesity with low skeletal muscle function and mass, but its utilization is largely limited to the aging patient population, and consensus on its definition and diagnostic criteria remains insufficient. Knowledge on prevalence of sarcopenic obesity in various clinical conditions and patient subgroups, on its clinical impacts in patient risk stratification and on effective prevention and treatment strategies remain therefore dramatically inadequate. In particular, optimal dietary options and medical nutritional support strategies to preserve muscle mass in obese individuals remain largely undefined. The European Society for Clinical Nutrition and Metabolism (ESPEN) and the European Association for the Study of Obesity (EASO) recognize and indicate obesity with altered body composition due to low skeletal muscle function and mass (sarcopenic obesity) as a scientific and clinical priority for researchers and clinicians. ESPEN and EASO therefore call for coordinated action aimed at reaching consensus on its definition, diagnostic criteria and optimal treatment with particular regard to nutritional therapy. We are convinced that achievement of these goals has strong potential to reduce the burden of morbidity and mortality in the rapidly increasing obese patient population. 10.1016/j.clnu.2018.04.018
    Sarcopenic Obesity: Epidemiologic Evidence, Pathophysiology, and Therapeutic Perspectives. Koliaki Chrysi,Liatis Stavros,Dalamaga Maria,Kokkinos Alexander Current obesity reports PURPOSE OF REVIEW:This review provides a comprehensive update on the definition, assessment, epidemiology, pathophysiology, clinical implications, and therapeutic approach of sarcopenic obesity (SO) and highlights the challenges, limitations, and knowledge gaps in SO research. RECENT FINDINGS:The confluence of a rapidly aging population with rising obesity rates has led to the phenotype of SO, defined as the concurrent presence of sarcopenia and obesity. Despite efforts, a standardized definition of SO is still lacking. Its prevalence varies widely between studies, depending on population characteristics and different definitions. The major pathogenetic mechanisms include age-related changes in body composition and hormonal milieu, positive energy balance, pro-inflammatory pathways, and insulin resistance. Lifestyle interventions, including caloric restriction and physical activity, are the cornerstones of SO treatment. SO is a multifaceted syndrome with serious clinical implications. The development and implementation of effective prevention and treatment strategies is a top priority based on its dramatically increasing health impact. 10.1007/s13679-019-00359-9
    Adipokines mediate inflammation and insulin resistance. Kwon Hyokjoon,Pessin Jeffrey E Frontiers in endocrinology For many years, adipose tissue was considered as an inert energy storage organ that accumulates and stores triacylglycerols during energy excess and releases fatty acids in times of systemic energy need. However, over the last two decades adipose tissue depots have been established as highly active endocrine and metabolically important organs that modulate energy expenditure and glucose homeostasis. In rodents, brown adipose tissue plays an essential role in non-shivering thermogenesis and in energy dissipation that can serve to protect against diet-induced obesity. White adipose tissue collectively referred too as either subcutaneous or visceral adipose tissue is responsible for the secretion of an array of signaling molecules, termed adipokines. These adipokines function as classic circulating hormones to communicate with other organs including brain, liver, muscle, the immune system, and adipose tissue itself. The dysregulation of adipokines has been implicated in obesity, type 2 diabetes, and cardiovascular disease. Recently, inflammatory responses in adipose tissue have been shown as a major mechanism to induce peripheral tissue insulin resistance. Although leptin and adiponectin regulate feeding behavior and energy expenditure, these adipokines are also involved in the regulation of inflammatory responses. Adipose tissue secretes various pro- and anti-inflammatory adipokines to modulate inflammation and insulin resistance. In obese humans and rodent models, the expression of pro-inflammatory adipokines is enhanced to induce insulin resistance. Collectively, these findings have suggested that obesity-induced insulin resistance may result, at least in part, from an imbalance in the expression of pro- and anti-inflammatory adipokines. Thus we will review the recent progress regarding the physiological and molecular functions of adipokines in the obesity-induced inflammation and insulin resistance with perspectives on future directions. 10.3389/fendo.2013.00071
    Brown adipose tissue as a secretory organ. Villarroya Francesc,Cereijo Rubén,Villarroya Joan,Giralt Marta Nature reviews. Endocrinology Brown adipose tissue (BAT) is the main site of adaptive thermogenesis and experimental studies have associated BAT activity with protection against obesity and metabolic diseases, such as type 2 diabetes mellitus and dyslipidaemia. Active BAT is present in adult humans and its activity is impaired in patients with obesity. The ability of BAT to protect against chronic metabolic disease has traditionally been attributed to its capacity to utilize glucose and lipids for thermogenesis. However, BAT might also have a secretory role, which could contribute to the systemic consequences of BAT activity. Several BAT-derived molecules that act in a paracrine or autocrine manner have been identified. Most of these factors promote hypertrophy and hyperplasia of BAT, vascularization, innervation and blood flow, processes that are all associated with BAT recruitment when thermogenic activity is enhanced. Additionally, BAT can release regulatory molecules that act on other tissues and organs. This secretory capacity of BAT is thought to be involved in the beneficial effects of BAT transplantation in rodents. Fibroblast growth factor 21, IL-6 and neuregulin 4 are among the first BAT-derived endocrine factors to be identified. In this Review, we discuss the current understanding of the regulatory molecules (the so-called brown adipokines or batokines) that are released by BAT that influence systemic metabolism and convey the beneficial metabolic effects of BAT activation. The identification of such adipokines might also direct drug discovery approaches for managing obesity and its associated chronic metabolic diseases. 10.1038/nrendo.2016.136
    The Role of Brown Adipose Tissue in Cardiovascular Disease Protection: Current Evidence and Future Directions. Pereira Renata O,McFarlane Samy I International journal of clinical research & trials 10.15344/2456-8007/2019/136
    The Impact of Obesity on the Association between Vitamin D Deficiency and Cardiovascular Disease. Paschou Stavroula A,Kosmopoulos Marinos,Nikas Ilias P,Spartalis Michael,Kassi Evanthia,Goulis Dimitrios G,Lambrinoudaki Irene,Siasos Gerasimos Nutrients The aim of this article is to review the literature regarding the relationship between vitamin D deficiency and cardiovascular disease (CVD) and its modification in the presence of obesity. Despite the strong association between vitamin D status and cardiovascular outcomes, vitamin D supplementation trials in the general population have failed to decrease the incidence of cardiovascular events and mortality. A comprehensive study of the published literature and a comparison with experimental data lead to the conclusion that obesity, due to its high prevalence and strong association with both vitamin D deficiency and CVD, may act as a critical confounder, which is responsible for the different results on this association. Adoption of a vitamin D preventive supplementation strategy for CVD is unlikely to yield any benefit to the general population. However, it might be particularly useful in obese adults with increased risk for CVD. 10.3390/nu11102458
    The long-term prognosis of cardiovascular disease and all-cause mortality for metabolically healthy obesity: a systematic review and meta-analysis. Zheng Ruizhi,Zhou Dan,Zhu Yimin Journal of epidemiology and community health BACKGROUND:Metabolically healthy obese phenotype (MHO) refers to obese individuals with absence of metabolic abnormalities such as dyslipidaemia, insulin resistance and hypertension. Many studies reported the long-term prognosis of MHO on diseases and mortality with inconsistent results. METHODS:We performed a meta-analysis to assess the risks of cardiovascular (CV) events and all-cause mortality for MHO individuals. Original prospective observational studies were searched in Medline, EMBASE, Web of Science and Cochrane library up to 30 September 2015. In this meta-analysis, the relative risk (RR) calculated on the basis of the incident number of disease events and deaths in participants and the corresponding multivariable-adjusted HR were both extracted to calculate pooled risk estimates. A random-effects model was used if there was heterogeneity among studies; otherwise, the fixed-effects model was used. RESULTS:22 prospective studies, involving 584 799 participants, were archived in the analyses. With metabolically healthy normal weight as the reference, the MHO phenotype was associated with a higher risk of CV events (RR 1.50, 95% CI 1.27 to 1.77; HR 1.60, 95% CI 1.38 to 1.84). However, MHO individuals were not associated with increased risk of all-cause mortality (RR 1.18, 95% CI 0.83 to 1.66; HR 1.07, 95% CI 0.92 to 1.25). CONCLUSIONS:The meta-analysis confirms a positive association between a metabolically healthy obese phenotype and the risk of CV events. However, higher risk for all-cause mortality is not evident in metabolically healthy obese individuals. 10.1136/jech-2015-206948
    Metabolically healthy obesity and risk of cardiovascular disease, cancer, and all-cause and cause-specific mortality: a protocol for a systematic review and meta-analysis of prospective studies. Tian Simiao,Liu Yazhuo,Feng Ao,Lou Keli,Dong Huimin BMJ open INTRODUCTION:Metabolically healthy obese phenotype (MHO) refers to obese individuals with an adequate metabolic profile and absence of metabolic syndrome. Many prospective studies have reported the benign condition relating the MHO phenotype and its potential role in reducing risk of cardiovascular disease, total cancer, and all-cause and cause-specific mortality. However, inconsistent results were found and the question remains controversial. We aim to conduct a systematic review and meta-analysis to clarify the associations these associations from relevant prospective studies. METHODS AND ANALYSIS:The Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Protocols 2015 statement was used to prepare this protocol. MEDLINE, Web of Science databases, EMBASE and Cochrane Database will be used for literature search from their inception up to December 2019 with restriction of published studies in English. Published prospective studies reporting adjusted relative risk (RR) estimates for the association between MHO phenotype and cardiovascular disease, total cancer, all-cause or cause-specific mortality will be included. The process of study screening, selection and data extraction will be performed independently by two reviewers, and the risk of bias for the studies included will be assessed using the Newcastle-Ottawa Quality Assessment Scale. HRs or RRs for disease events and mortality with 95% CIs will be considered as primary outcomes, and summary HRs/RRs will be pooled using random-effects models. The Cochrane's Q and the I statistics will be used to assess and quantify heterogeneity, respectively. Subgroup analysis will also be carried out according to study characteristics to investigate potential sources of heterogeneity. ETHICS AND DISSEMINATION:As this meta-analysis is performed based on the published studies, no ethical approval and patient safety considerations are required. The findings of the study will be reported and submitted to a peer-reviewed journals for publication. PROSPERO REGISTRATION NUMBER:CRD42019121766. 10.1136/bmjopen-2019-032742
    Risk of metabolic syndrome and early vascular markers for atherosclerosis in obese Indonesian adolescents. Murni Indah K,Sulistyoningrum Dian C,Susilowati Rina,Julia Madarina Paediatrics and international child health : The prevalence of childhood obesity has increased in low- and middle-income countries, including Indonesia. It is important to identify risk factors for cardiovascular disease in obese adolescents in this region.: To assess the risk of metabolic syndrome and early vascular markers for atherosclerosis in obese Indonesian adolescents: A cross-sectional study was undertaken in obese high school students aged 15-<18 years in Yogyakarta, Indonesia. All eligible adolescents were interviewed about their medical history, were physically examined and had a fasting blood sample taken. Arterial stiffness was measured during systole and diastole blood pressure, endothelial dysfunction was estimated using flow-mediated dilation (FMD) and arterial wall thickness using carotid artery intima-media thickness (CIMT).: A total of 4268 students were screened, 298 (7%) of whom were classified as obese. Of those, 229 had blood samples taken, 173 had FMD performed and 156 had CIMT examination. Adolescents with a higher body mass index or BMI score (>3.0) had a significantly poorer lipid profile, insulin level and homeostasis model assessment of insulin resistance (HOMA-IR) than those with a lower BMI score. There were no significant differences for early vasculature markers for atherosclerosis between these two groups.: The prevalence of risks of cardiovascular disease in obese adolescents was significant. The higher the BMI score, the higher the risks of cardiovascular disease. Interventions to reduce obesity and its cardiovascular disease morbidities are urgently needed in low- and middle-income countries.: BMI; body mass index; CIMT, carotid artery intima-media thickness; CDC, Centers for Disease Control and Prevention; FMD flow-mediated dilation; HDL high-density lipoprotein cholesterol; HbA1c haemoglobin A1c; HOMA-IR, homeostasis model assessment of insulin resistance; IOTF, International Obesity Task Force; LDL, low-density lipoprotein cholesterol; WHO, World Health Organization. 10.1080/20469047.2019.1697568
    Adipose Tissue Function and Expandability as Determinants of Lipotoxicity and the Metabolic Syndrome. Carobbio Stefania,Pellegrinelli Vanessa,Vidal-Puig Antonio Advances in experimental medicine and biology The adipose tissue organ is organised as distinct anatomical depots located all along the body axis and it is constituted of three different types of adipocytes : white, beige and brown which are integrated with vascular, immune, neural and extracellular stroma cells. These distinct adipocytes serve different specialised functions. The main function of white adipocytes is to ensure healthy storage of excess nutrients/energy and its rapid mobilisation to supply the demand of energy imposed by physiological cues in other organs, whereas brown and beige adipocytes are designed for heat production through uncoupling lipid oxidation from energy production. The concert action of the three type of adipocytes/tissues has been reported to ensure an optimal metabolic status in rodents. However, when one or multiple of these adipose depots become dysfunctional as a consequence of sustained lipid/nutrient overload, then insulin resistance and associated metabolic complications ensue. These metabolic alterations negatively affects the adipose tissue functionality and compromises global metabolic homeostasis. Optimising white adipose tissue expandability and its functional metabolic flexibility and/or promoting brown/beige mediated thermogenic activity counteracts obesity and its associated lipotoxic metabolic effects. The development of these therapeutic approaches requires a deep understanding of adipose tissue in all broad aspects. In this chapter we will discuss the characteristics of the different adipose tissue depots with respect to origins and precursors recruitment, plasticity, cellular composition and expandability capacity as well as molecular and metabolic signatures in both physiological and pathophysiological conditions. 10.1007/978-3-319-48382-5_7
    A Clinical Perspective: Contribution of Dysfunctional Perivascular Adipose Tissue (PVAT) to Cardiovascular Risk. Lian Xiaoming,Gollasch Maik Current hypertension reports Perivascular adipose tissue (PVAT) is now recognized as an important paracrine organ influencing the homeostasis of the vessel wall, regional blood flow and peripheral arterial resistance. There is remarkable phenotypic variability and plasticity of PVAT among various vascular beds, exhibiting phenotypes from white to brown and beige adipocytes. PVAT dysfunction is characterized by disturbed secretion of various adipokines, which, together with endothelial dysfunction, contribute to hypertension and cardiovascular disease (CVD). This brief review describes our current knowledge on PVAT in health and cardiovascular disease, with a special focus on different phenotypes and signaling pathways in adipocytes of PVAT associated with hypertension, obesity and cardiovascular disorders. 10.1007/s11906-016-0692-z
    Mechanisms linking adipose tissue inflammation to cardiac hypertrophy and fibrosis. Anthony Sarah R,Guarnieri Adrienne R,Gozdiff Anamarie,Helsley Robert N,Phillip Owens Albert,Tranter Michael Clinical science (London, England : 1979) Adipose tissue is classically recognized as the primary site of lipid storage, but in recent years has garnered appreciation for its broad role as an endocrine organ comprising multiple cell types whose collective secretome, termed as adipokines, is highly interdependent on metabolic homeostasis and inflammatory state. Anatomical location (e.g. visceral, subcutaneous, epicardial etc) and cellular composition of adipose tissue (e.g. white, beige, and brown adipocytes, macrophages etc.) also plays a critical role in determining its response to metabolic state, the resulting secretome, and its potential impact on remote tissues. Compared with other tissues, the heart has an extremely high and constant demand for energy generation, of which most is derived from oxidation of fatty acids. Availability of this fatty acid fuel source is dependent on adipose tissue, but evidence is mounting that adipose tissue plays a much broader role in cardiovascular physiology. In this review, we discuss the impact of the brown, subcutaneous, and visceral white, perivascular (PVAT), and epicardial adipose tissue (EAT) secretome on the development and progression of cardiovascular disease (CVD), with a particular focus on cardiac hypertrophy and fibrosis. 10.1042/CS20190578
    Mineralocorticoid Receptors in Metabolic Syndrome: From Physiology to Disease. Feraco Alessandra,Marzolla Vincenzo,Scuteri Angelo,Armani Andrea,Caprio Massimiliano Trends in endocrinology and metabolism: TEM Over the past decade, several studies have shown that activity of extra-renal mineralocorticoid receptors (MR) regulates vascular tone, adipogenesis, adipose tissue function, and cardiomyocyte contraction. In mice, abnormal activation of MR in the vasculature and in adipose tissue favors the occurrence of several components of the metabolic syndrome (MetS), such as hypertension, obesity, and glucose intolerance. Accordingly, high levels of aldosterone are associated with obesity and MetS in humans, suggesting that altered activation of aldosterone-MR system in extra-renal tissues leads to profound metabolic dysfunctions. In this context, in addition to the classical indications for heart failure and hypertension, MR antagonists (MRAs) nowadays represent a promising approach to tackle cardiovascular and metabolic disorders occurring in the MetS. 10.1016/j.tem.2019.11.006
    Obesity and atherogenic dyslipidemia. Bamba Vaneeta,Rader Daniel J Gastroenterology Obesity is associated with an increased risk of coronary heart disease, in part due to its strong association with atherogenic dyslipidemia, characterized by high triglycerides and low high-density lipoprotein (HDL) cholesterol. There has been substantial research effort focused on the mechanisms of the link between obesity and atherogenic dyslipidemia, both in the absence and presence of insulin resistance. After a brief overview of the epidemiology of atherogenic dyslipidemia, this article details the known molecular mechanisms of adipocyte function and its relationship to apoB-containing lipoprotein assembly and metabolism, both in the healthy as well as in the obese states. We also discuss the pathophysiology of low HDL cholesterol in obesity and the implications for cardiovascular disease risk. 10.1053/j.gastro.2007.03.056
    High-Density Lipoprotein Functionality as a New Pharmacological Target on Cardiovascular Disease: Unifying Mechanism That Explains High-Density Lipoprotein Protection Toward the Progression of Atherosclerosis. Favari Elda,Thomas Michael J,Sorci-Thomas Mary G Journal of cardiovascular pharmacology The formation of the atherosclerotic plaque that is characterized by the accumulation of abnormal amounts of cholesterol-loaded macrophages in the artery wall is mediated by both inflammatory events and alterations of lipid/lipoprotein metabolism. Reverse transport of cholesterol opposes the formation and development of atherosclerotic plaque by promoting high density lipoprotein (HDL)-mediated removal of cholesterol from peripheral macrophages and its delivery back to the liver for excretion into the bile. Although an inverse association between HDL plasma levels and the risk of cardiovascular disease (CVD) has been demonstrated over the years, several studies have recently shown that the antiatherogenic functions of HDL seem to be mediated by their functionality, not always associated with their plasma concentrations. Therefore, assessment of HDL function, evaluated as the capacity to promote cell cholesterol efflux, may offer a better prediction of CVD than HDL levels alone. In agreement with this idea, it has recently been shown that the assessment of serum cholesterol efflux capacity (CEC), as a metric of HDL functionality, may represent a predictor of atherosclerosis extent in humans. The purpose of this narrative review is to summarize the current evidence concerning the role of cholesterol efflux capacity that is important for evaluating CVD risk, focusing on pharmacological evidences and its relationship with inflammation. We conclude that HDL therapeutics are a promising area of investigation but strategies for identifying efficacy must move beyond the idea of simply raising static HDL-cholesterol levels and toward methods of measuring the dynamics of HDL particle remodeling and the generation of lipid-free apolipoprotein A-I (apoA-I). In this way, apoA-I, unlike mature HDL, can promote the greatest extent of cholesterol efflux relieving cellular cholesterol toxicity and the inflammation it causes. 10.1097/FJC.0000000000000573
    The exchangeable apolipoproteins in lipid metabolism and obesity. Su Xin,Peng Daoquan Clinica chimica acta; international journal of clinical chemistry Dyslipidemia, characterized by increased plasma levels of low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C), triglyceride (TG), and reduced plasma levels of high-density lipoprotein cholesterol (HDL-C), is confirmed as a hallmark of obesity and cardiovascular diseases (CVD), posing serious risks to the future health of humans. Thus, it is important to understand the molecular metabolism of dyslipidemia, which could help reduce the morbidity and mortality of obesity and CVD. Currently, several exchangeable apolipoproteins, such as apolipoprotein A1 (ApoA1), apolipoprotein A5 (ApoA5), apolipoprotein E (ApoE), and apolipoprotein C3 (ApoC3), have been verified to exert vital effects on modulating lipid metabolism and homeostasis both in plasma and in cells, which consequently affect dyslipidemia. In the present review, we summarize the findings of the effect of exchangeable apolipoproteins on affecting lipid metabolism in adipocytes and hepatocytes. Furthermore, we also provide new insights into the mechanisms by which the exchangeable apolipoproteins influence the pathogenesis of dyslipidemia and its related cardio-metabolic disorders. 10.1016/j.cca.2020.01.015
    Interaction between adipocytes and high-density lipoprotein:new insights into the mechanism of obesity-induced dyslipidemia and atherosclerosis. Zhang Tianhua,Chen Jin,Tang Xiaoyu,Luo Qin,Xu Danyan,Yu Bilian Lipids in health and disease Obesity is the most common nutritional disorder worldwide and is associated with dyslipidemia and atherosclerotic cardiovascular disease. The hallmark of dyslipidemia in obesity is low high density lipoprotein (HDL) cholesterol (HDL-C) levels. Moreover, the quality of HDL is also changed in the obese setting. However, there are still some disputes on the explanations for this phenomenon. There is increasing evidence that adipose tissue, as an energy storage tissue, participates in several metabolism activities, such as hormone secretion and cholesterol efflux. It can influence overall reverse cholesterol transport and plasma HDL-C level. In obesity individuals, the changes in morphology and function of adipose tissue affect plasma HDL-C levels and HDL function, thus, adipose tissue should be the main target for the treatment of HDL metabolism in obesity. In this review, we will summarize the cross-talk between adipocytes and HDL related to cardiovascular disease and focus on the new insights of the potential mechanism underlying obesity and HDL dysfunction. 10.1186/s12944-019-1170-9
    Prevalence of metabolic syndrome and its associated factors in overweight and obese adolescents. Dejavitte Rosemeire A S,Enes Carla C,Nucci Luciana B Journal of pediatric endocrinology & metabolism : JPEM Background Metabolic syndrome (MetS) is not only a problem of adulthood but is already present in children and adolescents. The aim of this study was to estimate the prevalence of MetS in adolescents and to identify the associated factors. Methods This was a cross-sectional study with 354 overweight and obese school-aged adolescents (10-19 years). Sociodemographic, anthropometric, clinical, biochemical and lifestyle variables were collected. MetS was identified according to the criteria proposed by the International Diabetes Federation (IDF). Multivariate logistic regression models were used to examine the associations between risk variables and MetS. Results The prevalence of MetS was 9.6%. Among adolescents with MetS, all of them had low high-density lipoprotein cholesterol (HDL-c), while 76.5% had hyperglycemia and 38.2% had hypertriglyceridemia. Only 12.1% did not present any component of MetS, while 40% had at least two components. Multivariate analysis showed that being a girl was a protective factor (odds ratio [OR] = 0.29, confidence interval [CI] = 0.13-0.65) for the presence of MetS, while obesity (OR = 3.63, CI = 1.62-8.17) and being insufficiently active (OR = 4.60, CI = 1.01-20.96) were the risk factors for MetS. Conclusions Obese and insufficiently active male adolescents are more likely to have MetS. Early identification of MetS components, especially among obese adolescents, is an important tool for the prevention of cardiovascular complications in adult life. 10.1515/jpem-2019-0369
    The impact of weight misperception on health-related quality of life in Korean adults (KNHANES 2007-2014): a community-based cross-sectional study. Park Susan,Lee Sejin,Hwang Jinseub,Kwon Jin-Won BMJ open BACKGROUND/OBJECTIVES:Weight perception, especially misperception, might affect health-related quality of life (HRQoL); however, related research is scarce and results remain equivocal. We examined the association between HRQoL and weight misperception by comparing obesity level as measured by body mass index (BMI) and weight perception in Korean adults. METHODS:Study subjects were 43 883 adults aged 19 years or older from cycles IV (2007-2009), V (2010-2012) and VI (2013-2014) of the Korean National Health and Nutrition Examination Survey. Multiple regression analyses comprising both logit and tobit models were conducted to evaluate the independent effect of obesity level as measured by BMI, weight perception and weight misperception on HRQoL after adjusting for demographics, socioeconomic status and number of chronic diseases. We also performed multiple regressions to explore the association between weight misperception and HRQoL stratified by BMI status. RESULTS:Obesity level as measured by BMI and weight perception were independently associated with low HRQoL in both separate and combined analyses. Weight misperception, including underestimation and overestimation, had a significantly negative impact on HRQoL. In subgroup analysis, subjects with BMI ranges from normal to overweight who misperceived their weight also had a high risk of low HRQoL. Overestimation of weight among obese subjects associated with low HRQoL, whereas underestimation of weight showed no significant association. CONCLUSIONS:Both obesity level as measured by BMI and perceiving weight as fat were significant risk factors for low HRQoL. Subjects who incorrectly perceived their weight relative to their BMI status were more likely to report impaired HRQoL, particularly subjects with BMI in the normal to overweight range. Based on these findings, we recommend political and clinical efforts to better inform individuals about healthy weight status and promote accurate weight perception. 10.1136/bmjopen-2017-016098
    Misperception of Healthy Weight: Associations Among Weight, Body Size Satisfaction and Body Appreciation in Older Adults. Brandão Maria Piedade,Fonseca Cardoso Margarida The journal of primary prevention Misperceived body weight in older people can affect their health and quality of life. We analysed the body image of older adults in Primary Health Care services in central Portugal, by considering participants' weight, body size satisfaction and body appreciation. This epidemiological and cross-sectional study involved 150 participants (56% women) with an average age of 74.9 years who completed questionnaires on body size and body appreciation. Forty-nine percent of participants were affected by overweight and 29% by obesity. The majority was not satisfied with their body size (71.2%), but had very high scores related to body appreciation. Around 40% of the participants with normal weight or overweight were satisfied with their body size. Multiple regression analysis revealed that both body size satisfaction and appreciation were negatively associated with obesity, but not with overweight. Older Portuguese adults are not able to assess if their weight is a risk to their health, but regardless of their perceived physical appearance, the elderly respect their body and are receptive to improving their health. 10.1007/s10935-019-00573-0
    Body mass index is associated with epigenetic age acceleration in the visceral adipose tissue of subjects with severe obesity. de Toro-Martín Juan,Guénard Frédéric,Tchernof André,Hould Frédéric-Simon,Lebel Stéfane,Julien François,Marceau Simon,Vohl Marie-Claude Clinical epigenetics BACKGROUND:There is solid evidence that obesity induces the acceleration of liver epigenetic aging. However, unlike easily accessible blood or subcutaneous adipose tissue, little is known about the impact of obesity on epigenetic aging of metabolically active visceral adipose tissue (VAT). Herein, we aimed to test whether obesity accelerates VAT epigenetic aging in subjects with severe obesity. RESULTS:A significant and positive correlation between chronological age and epigenetic age, estimated with a reduced version of the Horvath's epigenetic clock, was found in both blood (r = 0.78, p = 9.4 × 10) and VAT (r = 0.80, p = 1.1 × 10). Epigenetic age acceleration, defined as the residual resulting from regressing epigenetic age on chronological age, was significantly correlated with body mass index (BMI) in VAT (r = 0.29, p = 0.037). Multivariate linear regression analysis showed that, after adjusting for chronological age, sex and metabolic syndrome status, BMI remained significantly associated with epigenetic age acceleration in VAT (beta = 0.15, p = 0.035), equivalent to 2.3 years for each 10 BMI units. Binomial logistic regression showed that BMI-adjusted epigenetic age acceleration in VAT was significantly associated with a higher loss of excess body weight following biliopancreatic diversion with duodenal switch surgery (odds ratio = 1.21; 95% CI = 1.04-1.48; p = 0.03). CONCLUSIONS:Epigenetic age acceleration increases with BMI in VAT, but not in blood, as previously reported in liver. These results suggest that obesity is associated with epigenetic age acceleration of metabolically active tissues. Further studies that deepen the physiological relevance of VAT epigenetic aging will help to better understand the onset of metabolic syndrome and weight loss dynamics following bariatric surgery. 10.1186/s13148-019-0754-6
    SOCS2 modulates adipose tissue inflammation and expansion in mice. Val Cynthia Honorato,de Oliveira Marina Chaves,Lacerda Débora Romualdo,Barroso Andreia,Batista Nathalia Vieira,Menezes-Garcia Zélia,de Assis Diego Rodney Rodrigues,Cramer Allysson Thiago,Brant Fátima,Teixeira Mauro Martins,Glória Souza Danielle,Ferreira AdalieneVersiani M,Machado Fabiana Simão The Journal of nutritional biochemistry INTRODUCTION:Obesity is usually triggered by a nutrient overload that favors adipocyte hypertrophy and increases the number of pro-inflammatory cells and mediators into adipose tissue. These mediators may be regulated by suppressors of cytokine signaling (SOCS), such as SOCS2, which is involved in the regulation of the inflammatory response of many diseases, but its role in obesity is not yet known. We aimed to investigate the role of SOCS2 in metabolic and inflammatory dysfunction induced by a high-refined carbohydrate-containing diet (HC). MATERIAL AND METHODS:Male C57BL/6 wild type (WT) and SOCS2 deficient (SOCS2) mice were fed chow or an HC diet for 8 weeks. RESULTS:In general, SOCS2 deficient mice, independent of the diet, showed higher adipose tissue mass compared with their WT counterparts that were associated with decreased lipogenesis rate in adipose tissue, lipolysis in adipocyte culture and energy expenditure. An anti-inflammatory profile was observed in adipose tissue of SOCS2 by reduced secretion of cytokines, such as TNF and IL-6, and increased M2-like macrophages and regulatory T cells compared with WT mice. Also, SOCS2 deficiency reduced the differentiation/expansion of pro-inflammatory cells in the spleen but increased Th2 and Treg cells compared with their WT counterparts. CONCLUSION:The SOCS2 protein is an important modulator of obesity that regulates the metabolic pathways related to adipocyte size. Additionally, SOCS2 is an inflammatory regulator that appears to be essential for controlling the release of cytokines and the differentiation/recruitment of cells into adipose tissue during the development of obesity. 10.1016/j.jnutbio.2019.108304
    Crosstalk between intestinal microbiota, adipose tissue and skeletal muscle as an early event in systemic low-grade inflammation and the development of obesity and diabetes. Bleau Christian,Karelis Antony D,St-Pierre David H,Lamontagne Lucie Diabetes/metabolism research and reviews Obesity is associated with a systemic chronic low-grade inflammation that contributes to the development of metabolic disorders such as cardiovascular diseases and type 2 diabetes. However, the etiology of this obesity-related pro-inflammatory process remains unclear. Most studies have focused on adipose tissue dysfunctions and/or insulin resistance in skeletal muscle cells as well as changes in adipokine profile and macrophage recruitment as potential sources of inflammation. However, low-grade systemic inflammation probably involves a complex network of signals interconnecting several organs. Recent evidences have suggested that disturbances in the composition of the gut microbial flora and alterations in levels of gut peptides following the ingestion of a high-fat diet may be a cause of low-grade systemic inflammation that may even precede and predispose to obesity, metabolic disorders or type 2 diabetes. This hypothesis is appealing because the gastrointestinal system is first exposed to nutrients and may thereby represent the first link in the chain of events leading to the development of obesity-associated systemic inflammation. Therefore, the present review will summarize the latest advances interconnecting intestinal mucosal bacteria-mediated inflammation, adipose tissue and skeletal muscle in a coordinated circuitry favouring the onset of a high-fat diet-related systemic low-grade inflammation preceding obesity and predisposing to metabolic disorders and/or type 2 diabetes. A particular emphasis will be given to high-fat diet-induced alterations of gut homeostasis as an early initiator event of mucosal inflammation and adverse consequences contributing to the promotion of extended systemic inflammation, especially in adipose and muscular tissues. 10.1002/dmrr.2617
    Nutritional Models of Type 2 Diabetes Mellitus. Mühlhäusler Beverly Sara,Toop Carla,Gentili Sheridan Methods in molecular biology (Clifton, N.J.) In order to better understand the events that precede and precipitate the onset of type 2 diabetes (T2DM), several nutritional animal models have been developed. These models are generated by manipulating the diet of either the animal itself, or its mother during her pregnancy, and in comparison to traditional genetic and knock out models, have the advantage that they more accurately reflect the etiology of human T2DM. This chapter will discuss some of the most widely used nutritional models of T2DM: Diet-induced obesity (DIO) in adult rodents, and studies of offspring of mothers fed a low-protein, high-fat and/or high-sugar diet during pregnancy and/or lactation. Several common mechanisms have been identified through which these nutritional manipulations can lead to metabolic disease, including pancreatic beta-cell dysfunction, impaired insulin signaling in skeletal muscle, and the excess accumulation of visceral adipose tissue and consequent deposition of nonesterified fatty acids in peripheral tissues. In addition, there is an emerging concept that obesity/poor quality diets result in increased production and release of pro-inflammatory cytokines from adipose tissue leading to a state of chronic low-grade inflammation, and that this is likely to represent an important link between obesity/diet and metabolic dysfunction. The following chapter will discuss the most common nutritional models of T2DM in experimental animals, their application, and relationship to human etiology, and will highlight the important insights these models have provided into the pathogenesis of T2DM. 10.1007/978-1-4939-9882-1_3
    High-fat diet triggers obesity-related early infiltration of macrophages into adipose tissue and transient reduction of blood monocyte count. Liu Yanxia,Lu Xinping,Li Xialian,Du Peijie,Qin Guijun Molecular immunology Infiltration of adipose tissue macrophages (ATMs) is a typical feature of obesity, and circulating immune cells may indicate immune cell accumulation. However, it remains unclear whether this is true in the early stages of obesity. This study aimed to define the role of blood monocytes in obesity and the relationship between blood monocytes and ATMs in early-stage obesity. Two groups of male C57BL/6 J mice were fed on a 60 % high-fat diet (HFD) or a 10 % fat normal diet (ND), respectively, and monitored at 1, 2, 3, 7, and 12 weeks. Populations of circulating blood monocytes (CD11b + CD115+), ATMs (F4/80+CD11b+), and their subtypes were collected and analyzed using flow cytometry and immunofluorescence. Some cytokines (TNF-a, IL-1β) and chemokines (CCL2, CCL7) were also analyzed by real-time PCR. HFD induced obesity, dramatic fat expansion, and accumulation of ATMs in mice after 12 weeks. However, an acute and transient reduction of circulating monocyte count, elevated expression of CD11c in ly6c monocytes, and concurrent infiltration of ATMs into visceral adipose tissues (VAT) were observed as early as 1 week after initiating HFD. Further, HFD-induced changes in VAT, but not blood monocyte count, were partially reversed upon reverting to ND for 6 weeks. An acute but transient reduction of blood monocyte count was observed at the early stages of HFD feeding, which might be related to early infiltration of macrophages into adipose tissues. We believe that blood monocytes could be targeted as a new obesity treatment following additional studies. 10.1016/j.molimm.2019.11.002
    The association between obesity and lower working memory is mediated by inflammation: Findings from a nationally representative dataset of U.S. adults. Yang Yingkai,Shields Grant S,Wu Qian,Liu Yanling,Chen Hong,Guo Cheng Brain, behavior, and immunity Obesity is often accompanied by lower working memory (e.g., a lower ability to keep goal-relevant information in mind) relative to healthy weight individuals. Understanding this relative working memory impairment has important clinical implications, as working memory is thought to facilitate adherence to weight management programs. Theoretical models of obesity, self-regulation, and inflammation suggest that inflammation plays a role in obesity-related working memory impairments, but to date no study has tested this prediction. Therefore, the current study examined whether inflammation statistically mediated the relationship between obesity and working memory in a nationally representative dataset of U.S. adults from Wave IV of The National Longitudinal Study of Adolescent to Adult Health (N = 11,546, age range 25-34). Inflammation was quantified via C-reactive protein (CRP) level, and working memory was assessed using a modified digit span backward task. As expected, cross-sectional analyses showed that a body mass index (BMI) indicative of obesity-as well as greater BMI when BMI was analyzed continuously-and greater CRP were each related to lower working memory. Critically, we found that CRP levels statistically mediated the relationships between obesity/greater BMI and working memory, with CRP accounting for 44.1% of the variance explained in working memory by BMI. Moreover, these findings held both with and without controlling for relevant covariates, including demographic characteristics (e.g., age), socioeconomic status, and behavioral factors (e.g., smoking). Our results therefore point to inflammation as playing an important role in the relationship between obesity and working memory, and suggest that interventions aimed at reducing inflammation may help lessen the cognitive burden of obesity. 10.1016/j.bbi.2019.11.022
    Metabolic Syndrome Patients Have Lower Levels of Adropin When Compared With Healthy Overweight/Obese and Lean Subjects. Yosaee Somaye,Khodadost Mahmoud,Esteghamati Alireza,Speakman John R,Shidfar Farzad,Nazari Mahdiyeh Nasab,Bitarafan Vida,Djafarian Kurosh American journal of men's health Metabolic syndrome (MetS), a cluster of cardiometabolic risk factors, is a challenging public health issue. The aim of current study was to test the hypothesis that concentrations of plasma adropin and leptin differ between patients with MetS and comparable age- and sex-matched control groups. This case-control study involved 153 subjects (51 per group). The study group included obese subjects with MetS and the two control groups included weight-matched subjects without MetS ("healthy": obese) and normal weight subjects without MetS. Body composition parameters were measured using bioelectrical impedance analysis. Plasma levels of adropin, leptin, and their ratio were measured. Leptin was significantly different between obese patients with/without MetS groups and normal weight subjects. Patients with MetS had higher levels of leptin (14 ± 12.4) compared with those without MetS (11.2 ± 9.3 vs. 7 ± 7.1 obese and normal weight without MetS, respectively; p = .002). Compared with healthy obese and normal weight subjects, MetS subjects had lower levels of plasma adropin ( p < .001) and a lower plasma adropin to leptin ratio ( p < .001), which remained significant when adjusted for body fat mass by analysis of covariance ( p < .001). This study demonstrates low levels of adropin are correlated with MetS and hence identify it as a potentially protective agent against MetS development. Variation in adropin levels may partly explain the "healthy obese" phenomenon. 10.1177/1557988316664074
    Prospective Relation of Circulating Adipokines to Incident Metabolic Syndrome: The Framingham Heart Study. Zachariah Justin P,Quiroz Rene,Nelson Kerrie P,Teng Zhaoyang,Keaney John F,Sullivan Lisa M,Vasan Ramachandran S Journal of the American Heart Association BACKGROUND:Adipokines are elaborated by adipose tissue and are associated with glycemic, lipid, and vascular traits. We hypothesized that in a cross-sectional analysis circulating adipokines are altered among subsets of obesity stratified by presence versus absence of metabolic syndrome (MetS) and prospectively predict the incidence of MetS. METHODS AND RESULTS:Participants in the community-based Framingham Third Generation Cohort who attended examination cycle 1 were included in the study (2002-2005; N=3777, mean age, 40 years; 59% women). Circulating adiponectin, leptin, leptin receptor, fetuin-A, fatty acid-binding protein 4, and retinol binding protein 4 were assayed and related to incident MetS in follow-up (mean 6 years). The adipokines were compared among individuals with excess body weight (body mass index ≥25 kg/m) and prevalent MetS, excess body weight without MetS (metabolically healthy obese), and normal-weight with MetS (metabolically obese, normal-weight) with normal-weight participants without MetS as a referent. Metabolically healthy obese individuals (n=1467) had higher circulating levels of fetuin-A and fatty acid-binding protein 4 but lower levels of leptin, leptin receptor, and adiponectin (<0.001 for all). The adipokine panel was associated with incident MetS (263 new-onset cases; =0.002). Higher circulating concentrations of retinol-binding protein 4 and fetuin-A were associated with incidence of MetS (odds ratio per 1-SD increment log marker, 1.21; 95% CI, 1.03-1.41 [=0.02] and 1.17; 95% CI, 1.01-1.34 [=0.03], respectively). CONCLUSIONS:In our community-based sample of young to middle-aged adults, metabolically healthy obese individuals demonstrated an adverse adipokine profile. Higher circulating levels of retinol-binding protein 4 and fetuin-A marked future cardiometabolic risk. 10.1161/JAHA.116.004974
    Targeted High Performance Liquid Chromatography Tandem Mass Spectrometry-based Metabolomics differentiates metabolic syndrome from obesity. Zhong Fanyi,Xu Mengyang,Bruno Richard S,Ballard Kevin D,Zhu Jiangjiang Experimental biology and medicine (Maywood, N.J.) Both obesity and the metabolic syndrome are risk factors for type 2 diabetes and cardiovascular disease. Identification of novel biomarkers are needed to distinguish metabolic syndrome from equally obese individuals in order to direct them to early interventions that reduce their risk of developing further health problems. We utilized mass spectrometry-based targeted metabolic profiling of 221 metabolites to evaluate the associations between metabolite profiles and established metabolic syndrome criteria (i.e. elevated waist circumference, hypertension, elevated fasting glucose, elevated triglycerides, and low high-density lipoprotein cholesterol) in plasma samples from obese men ( n = 29; BMI = 35.5 ± 5.2 kg/m) and women ( n = 40; 34.9 ± 6.7 kg/m), of which 26 met the criteria for metabolic syndrome (17 men and 9 women). Compared to obese individuals without metabolic syndrome, univariate statistical analysis and partial least squares discriminant analysis showed that a specific group of metabolites from multiple metabolic pathways (i.e. purine metabolism, valine, leucine and isoleucine degradation, and tryptophan metabolism) were associated with the presence of metabolic syndrome. Receiver operating characteristic curves generated based on the PLS-DA models showed excellent areas under the curve (0.85 and 0.96, for metabolites only model and enhanced metabolites model, respectively), high specificities (0.86 and 0.93), and good sensitivities (0.71 and 0.91). Moreover, principal component analysis revealed that metabolic profiles can be used to further differentiate metabolic syndrome with 3 versus 4-5 metabolic syndrome criteria. Collectively, these findings support targeted metabolomics approaches to distinguish metabolic syndrome from obesity alone, and to stratify metabolic syndrome status based on the number of criteria met. Impact statement We utilized mass spectrometry-based targeted metabolic profiling of 221 metabolites to evaluate the associations between metabolite profiles and established MetS criteria. To our best knowledge, the findings of this study provide the first evidence that metabolic profiles can be used to differentiate participants with MetS from similarly obese individuals who do not meet established criteria of MetS. Furthermore, the study demonstrated that within MetS participants, their unique metabolic profiles correlated to the number of criteria used for MetS determination. Taken together, this metabolic profiling approach can potentially serve as a novel tool for MetS detection and monitoring, and provide useful metabolic information for future interventions targeting obesity and MetS. 10.1177/1535370217694098
    A correlation-based network for biomarker discovery in obesity with metabolic syndrome. Chen Pin-Yen,Cripps Allan W,West Nicholas P,Cox Amanda J,Zhang Ping BMC bioinformatics BACKGROUND:Obesity is associated with chronic activation of the immune system and an altered gut microbiome, leading to increased risk of chronic disease development. As yet, no biomarker profile has been found to distinguish individuals at greater risk of obesity-related disease. The aim of this study was to explore a correlation-based network approach to identify existing patterns of immune-microbiome interactions in obesity. RESULTS:The current study performed correlation-based network analysis on five different datasets obtained from 11 obese with metabolic syndrome (MetS) and 12 healthy weight men. These datasets included: anthropometric measures, metabolic measures, immune cell abundance, serum cytokine concentration, and gut microbial composition. The obese with MetS group had a denser network (total number of edges, n = 369) compared to the healthy network (n = 299). Within the obese with MetS network, biomarkers from the immune cell abundance group was found to be correlated to biomarkers from all four other datasets. Conversely in the healthy network, immune cell abundance was only correlated with serum cytokine concentration and gut microbial composition. These observations suggest high involvement of immune cells in obese with MetS individuals. There were also three key hubs found among immune cells in the obese with MetS networks involving regulatory T cells, neutrophil and cytotoxic cell abundance. No hubs were present in the healthy network. CONCLUSION:These results suggest a more complex interaction of inflammatory markers in obesity, with high connectivity of immune cells in the obese with MetS network compared to the healthy network. Three key hubs were identified in the obese with MetS network, involving Treg, neutrophils and cytotoxic cell abundance. Compared to a t-test, the network approach offered more meaningful results when comparing obese with MetS and healthy weight individuals, demonstrating its superiority in exploratory analysis. 10.1186/s12859-019-3064-2
    Highlighting inflammation and lipid metabolism. Ntambi James M Biochemical and biophysical research communications 10.1016/j.bbrc.2019.10.014
    Obesity, Inflammation, Toll-Like Receptor 4 and Fatty Acids. Rogero Marcelo Macedo,Calder Philip C Nutrients Obesity leads to an inflammatory condition that is directly involved in the etiology of cardiovascular diseases, type 2 diabetes mellitus, and certain types of cancer. The classic inflammatory response is an acute reaction to infections or to tissue injuries, and it tends to move towards resolution and homeostasis. However, the inflammatory process that was observed in individuals affected by obesity and metabolic syndrome differs from the classical inflammatory response in certain respects. This inflammatory process manifests itself systemically and it is characterized by a chronic low-intensity reaction. The toll-like receptor 4 (TLR4) signaling pathway is acknowledged as one of the main triggers of the obesity-induced inflammatory response. The aim of the present review is to describe the role that is played by the TLR4 signaling pathway in the inflammatory response and its modulation by saturated and omega-3 polyunsaturated fatty acids. Studies indicate that saturated fatty acids can induce inflammation by activating the TLR4 signaling pathway. Conversely, omega-3 polyunsaturated fatty acids, such as eicosapentaenoic acid and docosahexaenoic acid, exert anti-inflammatory actions through the attenuation of the activation of the TLR4 signaling pathway by either lipopolysaccharides or saturated fatty acids. 10.3390/nu10040432
    A global perspective on the crosstalk between saturated fatty acids and Toll-like receptor 4 in the etiology of inflammation and insulin resistance. Li Bin,Leung Joseph C K,Chan Loretta Y Y,Yiu Wai Han,Tang Sydney C W Progress in lipid research Obesity is featured by chronic systemic low-grade inflammation that eventually contributes to the development of insulin resistance. Toll-like receptor 4 (TLR4) is an important mediator that triggers the innate immune response by activating inflammatory signaling cascades. Human, animal and cell culture studies identified saturated fatty acids (SFAs), the dominant non-esterified fatty acid (NEFA) in the circulation of obese subjects, as non-microbial agonists that trigger the inflammatory response via activating TLR4 signaling, which acts as an important causative link between fatty acid overload, chronic low-grade inflammation and the related metabolic aberrations. The interaction between SFAs and TLR4 may be modulated through the myeloid differentiation primary response gene 88-dependent and independent signaling pathway. Greater understanding of the crosstalk between dietary SFAs and TLR4 signaling in the pathogenesis of metabolic imbalance may facilitate the design of a more efficient pharmacological strategy to alleviate the risk of developing chronic diseases elicited in part by fatty acid overload. The current review discusses recent advances in the impact of crosstalk between SFAs and TLR4 on inflammation and insulin resistance in multiple cell types, tissues and organs in the context of metabolic dysregulation. 10.1016/j.plipres.2019.101020
    Effect of whole foods and dietary patterns on markers of subclinical inflammation in weight-stable overweight and obese adults: a systematic review. Cowan Stephanie F,Leeming Emily R,Sinclair Andrew,Dordevic Aimee L,Truby Helen,Gibson Simone J Nutrition reviews CONTEXT:Reduction of subclinical inflammation is a potential target for chronic disease management. Adiposity is a known modifier of meta-inflammation; however, the influence of dietary factors is less clear. OBJECTIVE:This review examines evidence from human trials evaluating effects of whole foods or dietary patterns on circulating inflammatory markers in weight-stable overweight and obese adults. It is the first review to investigate effects of diet on inflammation, independent of changes in adiposity. DATA SOURCES:The Ovid MEDLINE, EMBASE, CINAHL, and Cochrane databases were searched. DATA EXTRACTION:Data extraction was conducted using the Cochrane Collaboration Handbook for Systematic Reviews of Interventions. DATA ANALYSIS:Study quality was evaluated using the Cochrane Collaboration Risk of Bias Assessment tool. Thirty-three studies were included assessing effects of 17 foods and dietary patterns on 39 inflammatory markers. CONCLUSIONS:Overall, foods and dietary patterns were not found to have significant effects on inflammatory markers in weight-stable individuals. Inconsistencies among studies were largely due to methodological limitations. Future research should invest in longer intervention periods and standardization of inflammatory marker panels paired with novel technologies, while ensuring anthropometric measures are monitored and adequately controls are used. SYSTEMATIC REVIEW REGISTRATION:Prospero registration number CRD42017067765. 10.1093/nutrit/nuz030
    Health consequences of obesity in the elderly: a review of four unresolved questions. Zamboni M,Mazzali G,Zoico E,Harris T B,Meigs J B,Di Francesco V,Fantin F,Bissoli L,Bosello O International journal of obesity (2005) Obesity prevalence is growing progressively even among older age groups. Controversy exists about the potential harms of obesity in the elderly. Debate persists about the relation between obesity in old age and total or disease-specific mortality, the definition of obesity in the elderly, its clinical relevance, and about the need for its treatment. Knowledge of age-related body composition and fat distribution changes will help us to better understand the relationships between obesity, morbidity and mortality in the elderly. Review of the literature supports that central fat and relative loss of fat-free mass may become relatively more important than BMI in determining the health risk associated with obesity in older ages. Weight gain or fat redistribution in older age may still confer adverse health risks (for earlier mortality, comorbidities conferring independent adverse health risks, or for functional decline). Evaluation of comorbidity and weight history should be performed in the elderly in order to generate a comprehensive assessment of the potential adverse health effects of overweight or obesity. The risks of obesity in the elderly have been underestimated by a number of confounders such as survival effect, competing mortalities, relatively shortened life expectancy in older persons, smoking, weight change and unintentional weight loss. Identification of elderly subjects with sarcopenic obesity is probably clinically relevant, but the definition of sarcopenic obesity, the benefits of its clinical identification, as well as its relation to clinical consequences require further study. Studies on the effect of voluntary weight loss in the elderly are scarce, but they suggest that even small amounts of weight loss (between 5-10% of initial body weight) may be beneficial. In older as well as in younger adults, voluntary weight loss may help to prevent the adverse health consequences of obesity. 10.1038/sj.ijo.0803005
    Obesity paradox and aging. Bosello Ottavio,Vanzo Angiola Eating and weight disorders : EWD BACKGROUND:In association with the rapid lengthening of life expectancy and the ever-rising prevalence of obesity, many studies explored in the elderly the phenomenon usually defined as the obesity paradox. OBJECTIVE AND METHODS:This article is a narrative overview of seventy-two papers (1999-2019) that investigated the obesity paradox during the aging process. Twenty-nine documents are examined more in detail. RESULTS:The majority of studies suggesting the existence of an obesity paradox have evaluated just BMI as an index of obesity. Some aspects are often not assessed or are underestimated, in particular body composition and visceral adiposity, sarcopenic obesity, and cardio fitness. Many studies support that central fat and relative loss of fat-free mass may become relatively more important than BMI in determining the health risk associated with obesity in older ages. CONCLUSION:Inaccurate assessments may lead to a systematic underestimation of the impact of obesity on morbidity and premature mortality and, consequently, to clinical behaviors that are not respectful of the health of elderly patients. Knowledge of the changes in body composition and fat distribution will help to better understand the relationship between obesity, morbidity, and mortality in the elderly. LEVEL OF EVIDENCE:Level V, narrative overview. 10.1007/s40519-019-00815-4
    Obesity and cardiovascular diseases: implications regarding fitness, fatness, and severity in the obesity paradox. Lavie Carl J,McAuley Paul A,Church Timothy S,Milani Richard V,Blair Steven N Journal of the American College of Cardiology Obesity has been increasing in epidemic proportions, with a disproportionately higher increase in morbid or class III obesity, and obesity adversely affects cardiovascular (CV) hemodynamics, structure, and function, as well as increases the prevalence of most CV diseases. Progressive declines in physical activity over 5 decades have occurred and have primarily caused the obesity epidemic. Despite the potential adverse impact of overweight and obesity, recent epidemiological data have demonstrated an association of mild obesity and, particularly, overweight on improved survival. We review in detail the obesity paradox in CV diseases where overweight and at least mildly obese patients with most CV diseases seem to have a better prognosis than do their leaner counterparts. The implications of cardiorespiratory fitness with prognosis are discussed, along with the joint impact of fitness and adiposity on the obesity paradox. Finally, in light of the obesity paradox, the potential value of purposeful weight loss and increased physical activity to affect levels of fitness is reviewed. 10.1016/j.jacc.2014.01.022
    An Overview and Update on Obesity and the Obesity Paradox in Cardiovascular Diseases. Elagizi Andrew,Kachur Sergey,Lavie Carl J,Carbone Salvatore,Pandey Ambarish,Ortega Francisco B,Milani Richard V Progress in cardiovascular diseases Obesity increases a number of cardiovascular disease (CVD) risk factors, but patients with many types of CVD may have a better prognosis if classified as overweight or obese, a phenomenon known as the "obesity paradox". This paradoxical benefit of a medically unfavorable phenotype is particularly strong in the overweight and class I obesity, and less pronounced in the more severe or morbidly obese populations (class II-III and greater). Rather than an obesity paradox, it is possible that this phenomenon may represent a "lean paradox", in which individuals classified as normal weight or underweight may have a poorer prognosis with respect to CVD, as a result of a progressive catabolic state and lean mass loss. Cardiorespiratory fitness (CRF) is a fundamental part of this discussion. A greater CRF is associated with lower CVD risk, regardless of body mass index (BMI). Also, the assessment of body composition compartments (i.e., fat mass, fat-free mass, lean mass) and the presence of metabolic derangements may be better indicators of CVD risk than BMI alone. The focus of this review is to summarize the current evidence of the obesity paradox. Moreover, we discuss the utility and limitations of BMI for cardiometabolic risk stratification, in addition to concepts such as "metabolically healthy obesity" (MHO) and the "fat but fit" phenomenon, which describe patients who are diagnosed with obesity using BMI, but without major metabolic derangements and with greater CRF, respectively. Finally, we propose that obese patients presenting with an excess body fat, yet without metabolic abnormalities, should still be viewed as an "at risk" population, and as such should receive advice to change their lifestyle to improve their CRF and to prevent the development of impaired fasting glucose, diabetes mellitus and other CVD risk factors as a form of primary prevention. 10.1016/j.pcad.2018.07.003