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    Weight reduction with very-low-caloric diet and endothelial function in overweight adults: role of plasma glucose. Raitakari Maria,Ilvonen Thomas,Ahotupa Markku,Lehtimäki Terho,Harmoinen Aimo,Suominen Pauli,Elo Juhani,Hartiala Jaakko,Raitakari Olli T Arteriosclerosis, thrombosis, and vascular biology OBJECTIVE:Obesity is associated with endothelial dysfunction that may contribute to the development of atherosclerosis. We studied whether weight reduction improves endothelial function in overweight individuals. METHODS AND RESULTS:Flow-mediated endothelium-dependent vasodilation of the brachial artery was measured in 67 adults (age: 46+/-7 years, body mass index: 35.2+/-5.4 kg/m2) before and after a 6-week weight reduction program induced by very-low-calorie diet (daily energy: 580 kcal/2.3 MJ). Caloric restriction reduced body weight from 101+/-18 to 90+/-17 kg. Flow-mediated vasodilation increased from 5.5%+/-3.7 to 8.8%+/-3.7% (P<0.0001). Nitrate-mediated vasodilation was not significantly affected. The improvement in flow-mediated dilation was associated with the reduction in plasma glucose concentration (P=0.0003). This relationship was independent of changes in weight, serum lipids, oxidized LDL, C-reactive protein, adiponectin, blood pressure, and insulin. CONCLUSIONS:Weight reduction with very-low-calorie diet improves flow-mediated vasodilation in obese individuals. This improvement is related to the reduction in plasma glucose concentration. These observations suggest that changes in glucose metabolism may determine endothelial vasodilatory function in obesity. 10.1161/01.ATV.0000109749.11042.7c
    Olive oil lessened fatty liver severity independent of cardiometabolic correction in patients with non-alcoholic fatty liver disease: A randomized clinical trial. Rezaei Shahla,Akhlaghi Masoumeh,Sasani Mohammad Reza,Barati Boldaji Reza Nutrition (Burbank, Los Angeles County, Calif.) OBJECTIVES:Olive oil has health benefits for the correction of metabolic diseases. We aimed to evaluate the effect of olive oil consumption on the severity of fatty liver and cardiometabolic markers in patients with non-alcoholic fatty liver disease. METHODS:This randomized, double-blind, clinical trial was conducted on 66 patients with non-alcoholic fatty liver disease. Patients were divided to receive either olive or sunflower oil, each 20 g/d for 12 wk. A hypocaloric diet (-500 kcal/d) was recommended to all participants. Fatty liver grade, liver enzymes, anthropometric parameters, blood pressure, serum lipid profile, glucose, insulin, malondialdehyde, total antioxidant capacity, and interleukin-6 were assessed pre- and postintervention. RESULTS:Fatty liver grade, weight, waist circumference, and blood pressure significantly decreased in both groups. Sunflower oil significantly reduced serum aspartate and alanine aminotransferases and olive oil only decreased serum aspartate aminotransferase. Fat-free mass and skeletal muscle mass significantly reduced after the consumption of sunflower oil and serum triacylglycerols and fat mass significantly declined after the ingestion of olive oil. Among these variables, only changes in fatty liver grade (-0.29 ± 0.46 in sunflower oil versus -0.75 ± 0.45 in olive oil; P < 0.001), skeletal muscle mass (-0.71 ± 1.36 in sunflower oil versus +0.45 ± 2.8 in olive oil; P = 0.04), and body fat percentage (+0.38 ± 5.2% in sunflower oil versus -3.4 ± 5.5% in olive oil; P = 0.04) were significantly different between the groups. CONCLUSIONS:Olive oil may alleviate the severity of fatty liver independent of correcting cardiometabolic risk factors. Low-calorie diets may benefit patients with non-alcoholic fatty liver disease additionally through mitigation of obesity, blood pressure, and liver enzymes. 10.1016/j.nut.2018.02.021
    Effects of weight loss and exercise on apelin serum concentrations and adipose tissue expression in human obesity. Krist Joanna,Wieder Katharina,Klöting Nora,Oberbach Andreas,Kralisch Susan,Wiesner Tobias,Schön Michael R,Gärtner Daniel,Dietrich Arne,Shang Edward,Lohmann Tobias,Dreßler Miriam,Fasshauer Mathias,Stumvoll Michael,Blüher Matthias Obesity facts OBJECTIVE:Apelin is an adipokine which plays a role in the regulation of glucose homeostasis and may contribute to the link between increased adipose tissue mass and obesity related metabolic diseases. Here we investigate the role of omental and subcutaneous (SC) adipose tissue apelin and its receptor APJ mRNA expression in human obesity and test the hypothesis that changes in circulating apelin are associated with reduced fat mass in three weight loss intervention studies. METHODS:Apelin serum concentration was measured in 740 individuals in a cross-sectional (n = 629) study including a subgroup (n = 161) for which omental and SC apelin mRNA expression has been analyzed and in three interventions: 12 weeks exercise (n = 60), 6 months calorie-restricted diet (n = 19), 12 months after bariatric surgery (n = 32). RESULTS:Apelin mRNA is significantly higher expressed in adipose tissue of patients with type 2 diabetes and correlates with circulating apelin, BMI, body fat, C-reactive protein, and insulin sensitivity. Obesity surgery-induced weight loss causes a significant reduction in omental and SC apelin expression. All interventions led to significantly reduced apelin serum concentrations which significantly correlate with improved insulin sensitivity, independently of changes in BMI. CONCLUSIONS:Reduced apelin expression and serum concentration may contribute to improved insulin sensitivity beyond significant weight loss. 10.1159/000348667
    Isocaloric Diets High in Animal or Plant Protein Reduce Liver Fat and Inflammation in Individuals With Type 2 Diabetes. Markova Mariya,Pivovarova Olga,Hornemann Silke,Sucher Stephanie,Frahnow Turid,Wegner Katrin,Machann Jürgen,Petzke Klaus Jürgen,Hierholzer Johannes,Lichtinghagen Ralf,Herder Christian,Carstensen-Kirberg Maren,Roden Michael,Rudovich Natalia,Klaus Susanne,Thomann Ralph,Schneeweiss Rosemarie,Rohn Sascha,Pfeiffer Andreas F H Gastroenterology BACKGROUND & AIMS:Nonalcoholic fatty liver disease (NAFLD) is associated with increased risk of hepatic, cardiovascular, and metabolic diseases. High-protein diets, rich in methionine and branched chain amino acids (BCAAs), apparently reduce liver fat, but can induce insulin resistance. We investigated the effects of diets high in animal protein (AP) vs plant protein (PP), which differ in levels of methionine and BCAAs, in patients with type 2 diabetes and NAFLD. We examined levels of liver fat, lipogenic indices, markers of inflammation, serum levels of fibroblast growth factor 21 (FGF21), and activation of signaling pathways in adipose tissue. METHODS:We performed a prospective study of individuals with type 2 diabetes and NAFLD at a tertiary medical center in Germany from June 2013 through March 2015. We analyzed data from 37 subjects placed on a diet high in AP (rich in meat and dairy foods; n = 18) or PP (mainly legume protein; n = 19) without calorie restriction for 6 weeks. The diets were isocaloric with the same macronutrient composition (30% protein, 40% carbohydrates, and 30% fat). Participants were examined at the start of the study and after the 6-week diet period for body mass index, body composition, hip circumference, resting energy expenditure, and respiratory quotient. Body fat and intrahepatic fat were detected by magnetic resonance imaging and spectroscopy, respectively. Levels of glucose, insulin, liver enzymes, and inflammation markers, as well as individual free fatty acids and free amino acids, were measured in collected blood samples. Hyperinsulinemic euglycemic clamps were performed to determine whole-body insulin sensitivity. Subcutaneous adipose tissue samples were collected and analyzed for gene expression patterns and phosphorylation of signaling proteins. RESULTS:Postprandial levels of BCAAs and methionine were significantly higher in subjects on the AP vs the PP diet. The AP and PP diets each reduced liver fat by 36%-48% within 6 weeks (for AP diet P = .0002; for PP diet P = .001). These reductions were unrelated to change in body weight, but correlated with down-regulation of lipolysis and lipogenic indices. Serum level of FGF21 decreased by 50% in each group (for AP diet P < .0002; for PP diet P < .0002); decrease in FGF21 correlated with loss of hepatic fat. In gene expression analyses of adipose tissue, expression of the FGF21 receptor cofactor β-klotho was associated with reduced expression of genes encoding lipolytic and lipogenic proteins. In patients on each diet, levels of hepatic enzymes and markers of inflammation decreased, insulin sensitivity increased, and serum level of keratin 18 decreased. CONCLUSIONS:In a prospective study of patients with type 2 diabetes, we found diets high in protein (either animal or plant) significantly reduced liver fat independently of body weight, and reduced markers of insulin resistance and hepatic necroinflammation. The diets appear to mediate these changes via lipolytic and lipogenic pathways in adipose tissue. Negative effects of BCAA or methionine were not detectable. FGF21 level appears to be a marker of metabolic improvement. ClinicalTrials.gov ID NCT02402985. 10.1053/j.gastro.2016.10.007
    Body fat distribution, serum glucose, lipid and insulin response to meals in Alström syndrome. Paisey R B,Hodge D,Williams K Journal of human nutrition and dietetics : the official journal of the British Dietetic Association BACKGROUND:Alström syndrome is an autosomal recessive condition characterized by obesity, insulin resistance and hypertriglyceridaemia. Responses to fat and carbohydrate ingestion are important in planning dietetic advice and may help to explain the mechanism of metabolic disorder in the syndrome. METHODS:After a 12-h fast, five Alström subjects received a 3.1 MJ (742 kcal), 75.8% fat breakfast on day 1, and a 3.3 MJ (794 kcal), 77.5% carbohydrate breakfast on day 2. Serum glucose, triglyceride and insulin levels were measured at baseline, and 2 and 3.5 h post-meal. Abdominal computerized tomography in three subjects and magnetic resonance imaging in one demonstrated distribution of abdominal fat. RESULTS:Body fat was distributed subcutaneously, as well as viscerally. There were no changes in serum glucose, insulin or triglycerides after the high fat meal. Triglycerides remained stable after the high carbohydrate meal but glucose and log insulin levels increased [8.4 +/- 4.1 to 13.4 +/- 6.9 mmol L(-1) (P < 0.05) and 2.6 +/- 0.27 to 3.15 +/- 0.42 pmol L(-1) (P < 0.05), respectively]. CONCLUSIONS:Dietetic advice in Alström syndrome must include calorie restriction to reduce obesity, which is predominantly subcutaneous. This study has shown that low carbohydrate advice may prove more effective than fat restriction in control of hyperglycaemia and hyperinsulinism. A single high energy meal does not exacerbate hypertriglyceridaemia. 10.1111/j.1365-277X.2008.00866.x
    Low advanced Glycation end product diet improves the central obesity, insulin resistance and inflammatory profiles in Iranian patients with metabolic syndrome: a randomized clinical trial. Goudarzi Razieh,Sedaghat Meghdad,Hedayati Mehdi,Hekmatdoost Azita,Sohrab Golbon Journal of diabetes and metabolic disorders The study aimed to investigate the effects of 8-weeks AGEs restricted diet on glycemic control as well as lipid profile, inflammatory and oxidative stress biomarkers and IR in overweight patients with Mets. In this randomized, controlled clinical trial 40 clients were randomly assigned to take either a low AGE (L-AGE) or a regular AGE (Reg-AGE) diet. Also, both groups were advised to follow an energy-restricted diet. At baseline and after 8-weeks of intervention, anthropometric parameters, dietary intake, plasma concentrations of malondialdehyde, carboxymethyllysine, TNF-α, hs-CRP and levels of serum glucose, lipid and insulin were assessed. AGEs restriction resulted in significant changes in mean differences levels of CML ( < 0.004), FBG ( < 0.01), HOMA-IR ( < 0.04), TNF-α (p < 0.01) and MDA ( < 0.02) in comparison to Reg-AGE. Moreover, weight ( < 0.0001) and WC ( < 0.001) significantly declined in the intervention group. Our results indicate that dAGEs restriction plus a low-calorie diet is superior to a low-calorie diet in amelioration of central obesity and IR at least partially through reduction of OS and inflammation in Mets subjects. 10.1007/s40200-020-00614-0
    Effects of lifestyle changes including specific dietary intervention and physical activity in the management of patients with chronic hepatitis C--a randomized trial. Rusu Emilia,Jinga Mariana,Enache Georgiana,Rusu Florin,Dragomir Andreea Diana,Ancuta Ioan,Draguţ Ramona,Parpala Cristina,Nan Raluca,Sima Irina,Ateia Simona,Stoica Victor,Cheţa Dan Mircea,Radulian Gabriela Nutrition journal BACKGROUND:In patients with chronic hepatitis C (CHC), obesity is involved in the pathogenesis of insulin resistance, fatty liver disease and progression of fibrosis. The objective of this study was to compare a normoglucidic low-calorie diet (NGLCD) with a low-fat diet (LFD) among participants with CHC. Aimed to measure the impact of dietary changes in reduction of insulin resistance, obesity but also in steatosis and fibrosis. METHODS:Randomized, controlled trial in three medical centers with assessments at baseline, 6 months and 12 months. Participants were patients over 35 years with chronic hepatitis C (n = 120) with BMI over 25 kg/m². We evaluated the effects of NGLCD vs. LFD in weight management and metabolic improvement. The primary endpoint was to measure the impact of dietary changes through nutritional intervention in reversibility of insulin resistance, obesity, steatosis, and fibrosis. We performed anthropometric measurements, fasting glucose profile, serum lipids, liver profile, blood count at baseline, 6 and 12 months. Steatosis was evaluated using ultrasonographic criteria. Liver fibrosis was non-invasively assessed. RESULTS:After 6 and 12 months of intervention, both groups had a significant decrease in caloric consumption. At 6 months, weight loss was greater in the NGLCD group (-5.02 ± 3.43 kg vs. -4.1 ± 2.6 kg; p = 0.002) compared to the LFD group. At 1-year, however, weight loss was similar in both groups (-3.9 ± 3.3 kg vs. -3.1 ± 2.6 kg; p = 0.139). At 12 months, fasting plasma glucose, fasting plasma insulin, and HOMA-IR had significant improvements in both groups. With both diets aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transpeptidase (GGT) decreased with significant differences; also there were significant improvements in AST/ALT ratio, Forns fibrosis index. The two diets were associated with reduction of both the prevalence and the severity of steatosis (all p < 0.001). At 12 months, total cholesterol, HDL-cholesterol, triglycerides improved in both groups (all p < 0.05). CONCLUSIONS:The present study establishes the benefits of low-calorie diet and low-fat diet in management of patients with hepatitis C regarding improvement of insulin resistance, steatosis and also fibrosis.Overweight or obese patients with CHC undergoing a lifestyle intervention (specific dietary intervention and physical activity) for 1-year had significant improvements in body weight, lipid and hepatic profile. TRIAL REGISTRATION:PNCI2-3343/41008/2007. 10.1186/1475-2891-12-119
    Relationship of adipokine to insulin sensitivity and glycemic regulation in obese women--the effect of body weight reduction by caloric restriction. Golubović Milena Velojić,Dimić Dragan,Antić Slobodan,Radenković Sasa,Djindjić Boris,Jovanović Miodrag Vojnosanitetski pregled BACKGROUND/AIM:Visceral fat is highly active metabolic and endocrine tissue which secretes many adipokines that act both on local and systemic level. It is believed that adipokines and "low-grade inflammatory state" represent a potential link between obesity, metabolic syndrome, insulin resistance and cardiovascular disease. Leptin and adiponectin are considered to be the most important adipokines with the potential metabolic and cardiovascular effects. Body weight loss improves insulin sensitivity and decreases risk for most complications associated with obesity. The aim of this study was to determine the effects of moderate loss of body weight on the level of leptin and adiponectin, insulin sensitivity and abnormalities of glycoregulation in obese women, to determine whether and to what extent the secretory products of adipose tissue, leptin and adiponectin contribute to insulin sensitivity, as well as to assess their relationship and influence on glycemia and insulinemia during the period of losing body weight using a calorie restricted diet. METHODS:The study involved 90 obese female subjects (BMI > or = 30 kg/m2) of different age with weight loss no less than 5% during a six-month period by application of restricted dietary regime. The calorie range was between 1,100-1,350 kcal. Serum levels of leptin and adiponectin, fasting glucose, fasting insulinemia, and Homeostasis Model Assessment of Insulin Resistance (HOMA-R) index were determined in all the subjects initially and after weight reduction. The presence of glycemic disorders was assessed on the basis of oral glucose tolerance test--OGTT. RESULTS:Applying a 6-month restrictive dietary regime the subjects achieved an average weight loss of 8.73 +/- 1.98 kg and 8.64 +/- 1.96%, which led to the reduction of fasting glycemia, fasting insulinemia and HOMA-R index at the maximum level of statistical significance (p < 0.001). The achieved reduction led to a statistically significant decrease of leptin level and increase of adiponectin level (p < 0.001). The correction of the established pre-diabetic disorders of glycoregulation was not statistically significant. There was a statistically significant correlation between the anthropometric parameters, leptin, adiponectin, fasting glycemia, fasting insulinemia and HOMA-R index. There was a positive correlation between leptin, fasting insulinemia and HOMA-R, as well as a statistically significant negative correlation between adiponectin, fasting insulinemia and HOMA-R index (p < 0.01). CONCLUSION:Body weight increase and central fat accumulation lead to changes in serum levels of leptin and adiponectin, reduction of insulin sensitivity and development of glycemic dysregulation. Secretory products of adipose tissue, leptin and adiponectin contribute to the genesis of these disorders. The obtained results show that the effect of adiponectin on insulin sensitivity is more significant. The analysis of the effects of weight loss on the investigated parameters shows that moderate weight reduction by restrictive dietary regime lead to changes of investigated parameters at the maximum level of statistical significance. Such results emphasize the importance of weight reduction in obese persons, as well as the need for consistent implementation of restricted dietary regime in the process of treatment of obesity.
    Changes in liver volume and body composition during 4 weeks of low calorie diet before laparoscopic gastric bypass. Edholm David,Kullberg Joel,Karlsson F Anders,Haenni Arvo,Ahlström Håkan,Sundbom Magnus Surgery for obesity and related diseases : official journal of the American Society for Bariatric Surgery BACKGROUND:Weight loss before laparoscopic Roux-en-Y gastric bypass (LRYGB) is desirable, because it can reduce liver volume and thereby facilitate the procedure. The optimal duration of a low-calorie diet (LCD) has not been established. The objective of this study was to assess changes in liver volume and body composition during 4 weeks of LCD. METHODS:Ten women (aged 43±8.9 years, 114±12.1 kg, and body mass index 42±2.6 kg/m(2)) were examined on days 0, 3, 7, 14, and 28 after commencing the LCD. At each evaluation, body composition was assessed through bioelectric impedance analysis, and liver volume and intrahepatic fat content were assessed by magnetic resonance imaging. Serum and urine samples were obtained. Questionnaires regarding quality of life and LCD-related symptoms were administered. RESULTS:In total, mean weight decreased by 7.4±1.2 kg (range 5.7-9.1 kg), and 71% of the weight loss consisted of fat mass according to bioelectric impedance analysis. From day 0 to day 3, the weight loss (2.0 kg) consisted mainly of water. Liver volume decreased by 18%±6.2%, from 2.1 to 1.7 liters (P<.01), during the first 2 weeks with no further change thereafter. A continuous 51%±16% decrease was seen in intrahepatic fat content. Systolic blood pressure, insulin, and lipids improved, while liver enzymes, glucose levels, and quality of life were unaffected. CONCLUSION:A significant decrease in liver volume (18%) occurred during the first 2 weeks of LCD treatment, and intrahepatic fat gradually decreased throughout the study period. A preoperative 2-week LCD treatment seems sufficient in similar patients. 10.1016/j.soard.2014.07.018
    Rising serum 25-hydroxy-vitamin D levels after weight loss in obese women correlate with improvement in insulin resistance. Tzotzas Themistoklis,Papadopoulou Fotini G,Tziomalos Kostantinos,Karras Spiros,Gastaris Kostantinos,Perros Petros,Krassas Gerasimos E The Journal of clinical endocrinology and metabolism OBJECTIVE:The objective of the study was to examine changes of 25-hydroxy-vitamin D (25OHD) and PTH blood levels 4 and 20 wk after low-calorie diet-induced weight loss. METHODS:Forty-four obese women [aged 40.6 +/- 11.4 yr, body mass index (BMI) 36.7 +/- 4.9 kg/m(2)] and 25 controls (BMI 22.9 +/- 1.5 kg/m(2)) were examined. Anthropometric and cardiometabolic parameters and 25OHD and PTH levels were determined at baseline and 4 and 20 wk after a low-calorie diet. RESULTS:At baseline, 25OHD levels were lower in obese compared with control subjects (17 +/- 6.0 vs. 23.8 +/- 8.7 ng/ml, P < 0.001), whereas no differences were found in PTH levels. In all women, a negative correlation was found between 25OHD levels and body weight (BW) (r -0.32, P < 0.001), BMI (r -0.37, P < 0.001), waist circumference (r -0.26, P < 0.05), and percent fat mass (r -0.38, P = 0.001) as determined by bioelectrical impedance analysis. The 4-wk low-calorie diet (n = 37) reduced BW and led to significant improvements in the homeostasis model assessment (HOMA) index and lipid levels. The 20-wk low-calorie diet (n = 26) resulted in reduction of BW and BMI by 10%, HOMA index (4.7 +/- 3.8 vs. 3.10 +/- 1.7, P < 0.01), and lipids levels (except high density lipoprotein cholesterol) and increase in 25OHD (15.4 +/- 6.0 vs. 18.3 +/- 5.1 ng/ml, P < 0.05), compared with baseline. PTH levels were unchanged. The increase of 25OHD levels was associated with the reduction of insulin levels and HOMA index (r -0.43, P < 0.05). CONCLUSIONS:Blood 25OHD levels were low in obese women and correlated inversely with severity measures of obesity. Weight loss of 10% after low-calorie diet increased 25OHD levels, and this increase was mainly associated with improvement of insulin resistance. 10.1210/jc.2010-0757
    The effect of synbiotic on glycemic profile and sex hormones in overweight and obese breast cancer survivors following a weight-loss diet: A randomized, triple-blind, controlled trial. Raji Lahiji Mahsa,Najafi Safa,Janani Leila,Yazdani Bahareh,Razmpoosh Elham,Zarrati Mitra Clinical nutrition (Edinburgh, Scotland) BACKGROUND:The investigation was designed to assess the effects of synbiotic supplementation on glycemic profile, insulin-like growth factor-1 (IGF-1) and sex hormones in overweight and obese postmenopausal breast cancer survivors (BCSs) who had hormone-receptor-positive breast cancer. METHODS:This randomized, triple-blind, placebo-controlled trial was conducted on 76 overweight and obese BCSs aged 57.43 (5.82) years. All participants were given a specified low calorie diet and were randomly assigned into two groups to intake 10 CFU/day of synbiotic supplement (n = 38) or placebo (n = 38) for 8 weeks. Body composition, physical activity, glycemic profile, IGF-1, estradiol, testosterone and dehydroepiandrosterone sulfate (DHEA-S) were measured at baseline and after 8 weeks. RESULTS:A significant reduction in serum insulin (median change (Q1, Q3) from baseline of -1.05 (-2.36, 0.32) μIU/mL; P = 0.006) and insulin resistance (HOMA-IR) (mean change (SD) from baseline of -4.0 (0.9); P = 0.007) were seen over the 8 weeks in the synbiotic group. However, no significant changes were observed in serum insulin, fasting plasma glucose, HbA1c, HOMA-IR, IGF-1, estradiol, testosterone, DHEA-S and sex hormone binding globulin between-groups at the end of the intervention. CONCLUSIONS:Overall, as the 8-week synbiotic consumption compared with placebo had insignificant-reducing effects on glycemic profile, IGF-1 and sex hormones among overweight and obese postmenopausal BCSs, synbiotics may exert considerable beneficial consequences, which need to be further assessed in future clinical trials. TRIAL REGISTRATION:IRCT, IRCT2015090223861N1. Registered 02 February 2017, http://www.irct.ir: IRCT2015090223861N1. 10.1016/j.clnu.2020.05.043
    Caloric restriction stabilizes body weight and accelerates behavioral recovery in aged rats after focal ischemia. Ciobanu Ovidiu,Elena Sandu Raluca,Tudor Balseanu Adrian,Zavaleanu Alexandra,Gresita Andrei,Petcu Eugen Bogdan,Uzoni Adriana,Popa-Wagner Aurel Aging cell Obesity and hyperinsulinemia are risk factors for stroke. We tested the hypothesis that caloric restriction, which reduces the incidence of age-related obesity and metabolic syndrome, may represent an efficient and cost-effective strategy for preventing stroke and its devastating consequences. To this end, we placed aged, obese Sprague-Dawley aged rats on a calorie-restricted diet for 8 weeks prior to the experimental infarction. Stroke in this animal model caused a progressive decrease in weight that reached a minimum at day 6 for the young rats, and at day 10 for the aged, ad libitum-fed rats. However, in aged animals that were calorie-restricted prior to stroke, body weight did not decrease after stroke, but we noted accelerated body weight gain shortly thereafter starting at day 5 poststroke. Moreover, calorie-restricted aged animals showed improved behavioral recovery in tasks requiring complex sensorimotor skills, or in tasks requiring cutaneous sensitivity and sensorimotor integration or spatial memory. Likewise, calorie-restricted aged rats showed significant poststroke increases in serum glucose, insulin, and IGF1 levels, as well as CR-specific changes in the expression of gene transcripts involved in glycogen metabolism, IGF signaling, apoptosis, arteriogenesis, and hypoxia. In conclusion, our study shows that recovery from stroke is enhanced in aged rats by a dietary regimen that reduces body weight prior to infarct. 10.1111/acel.12678
    Effects of a Low-Calorie, Low-Carbohydrate Soy Containing Diet on Systemic Inflammation Among Patients with Nonalcoholic Fatty Liver Disease: A Parallel Randomized Clinical Trial. Kani Ali Hashemi,Alavian Seyed Moayed,Esmaillzadeh Ahmad,Adibi Peyman,Haghighatdoost Fahimeh,Azadbakht Leila Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme Few studies have focused on the effects of a soy containing diet on inflammation and serum leptin level among patients with nonalcoholic fatty liver disease (NAFLD). Therefore, we aimed to determine the effects of such a diet in patients with NAFLD. Forty-five patients with NAFLD participated in this parallel randomized clinical trial for 8 weeks. Patients were randomly allocated to these 3 groups: 1) a low-calorie diet, 2) low-calorie low-carbohydrate diet, and 3) low-calorie low-carbohydrate soy containing diet. Low-calorie low-carbohydrate soy containing diet reduced fasting blood sugar (FBS) and serum insulin level significantly compared to other 2 groups (-11.6±2.8 vs. -6.3±1.7 and -3.1±1.0 mg/dl for FBS; and -5.1±1.2  vs. -1.2±0.3 and -1.7±0.5 mg/dl for serum insulin level). Serum hs-CRP level was also reduced significantly following low-calorie low-carbohydrate soy containing diet (-0.8±0.1 vs. -0.1±0.06 and -0.1±0.06 mg/dl). Both systolic and diastolic blood pressures were reduced significantly. Changes in leptin level tended to be different among 3 groups. After trial, 5 patients in each intervention group did not have NAFLD. From 6 patients in grade 2 at the beginning only 1 patient remained and others moved to grade 1. Low-calorie low-carbohydrate soy containing diet could reduce glycemic indices, hs CRP, systolic and diastolic blood pressure in a significant level in patients with NAFLD. However, these effects were dependent on baseline weight and further studies are needed to clarify the effect of such interventions in subjects with different BMI categories. 10.1055/s-0042-118707
    The influence of orlistat, metformin and diet on serum levels of insulin-like growth factor-1 in obeses women with and without insulin resistance. Kujawska-Luczak M,Szulinska M,Skrypnik D,Musialik K,Swora-Cwynar E,Kregielska-Narozna M,Markuszewski L,Grzymislawska M,Bogdanski P Journal of physiology and pharmacology : an official journal of the Polish Physiological Society A range of studies showed confusing data about the relationship between obesity, weight reduction and circulating total insulin-like growth factor -1 (IGF-1). The aim of the study was to compare the influence of orlistat (IO), metformin (IM), or calorie-restricted diet (LC) on IGF-1, with special respect to insulin-resistance status. One hundred and fourteen obese women aged from 18 to 40 years were divided into insulin sensitive (IS) and insulin resistant (IR) groups and received a low calorie diet (LC), or an isocaloric diet and 500 mg metformin twice daily (IM), or isocaloric diet with 120 mg orlistat three times daily (IO). Before and after the intervention anthropometric parameters, serum lipid profile, serum concentrations of alanine aminotransferase, aspartate aminotransferase, insulin, glucose, IGF-1, HOMA-IR (homeostatic model assessment), and visceral adiposity index (VAI), and their changes were registered. Although the reductions in weight and body fat were comparable in IS and IR groups, only women with IR showed a significant increase in IGF-1 concentration as a result of all interventions. We found significant positive correlations of ΔIGF-1 with initial and Δ values of: HOMA-IR, triglyceride/high-density cholesterol ratio, VAI. IR premenopausal women show significant increase in IGF-1 serum concentrations regardless the method of intervention. The increase in IGF-1 was parallel to the improvement of insulin resistance parameters. 10.26402/jpp.2018.5.08
    Effects of short-term mild calorie restriction diet and renutrition with ruminant milks on leptin levels and other metabolic parameters in mice. Gauffin Cano María Paola,Van Nieuwenhove Carina,Chaila Zulema,Bazán Cristina,González Silvia Nutrition (Burbank, Los Angeles County, Calif.) OBJECTIVE:The adaptation of an organism to a calorie-restricted diet is characterized by metabolic, endocrine, and immunologic changes. The objective of this study was to determine, in a mouse model, the changes in serum leptin levels in response to short-term mild calorie-restricted and renutrition diets using different ruminant milks. METHODS:Weaned Swiss albino mice were fed with a mild calorie-restricted diet for 12 d, after which they were renourished with cow, goat, sheep, or buffalo milk for 7 d. Body, thymus, and spleen weights and biochemical, hematologic, and endocrine parameters were evaluated. RESULTS:The mild calorie restriction did not significantly modify insulin and leptin levels. The renutrition diets increased insulin levels, being significant (P < 0.05) only when buffalo and sheep milks were used. Leptin concentrations increased in the control ad libitum (AD) group during the assayed period. After the administration of cow and goat milks, lower leptin levels were observed compared with the control AD group. All repletion diets significantly increased body, thymus, and spleen weights; however, spleen weight did not reach the values observed in the control AD group. Serum glucose and triacylglycerol levels increased after feeding with the renutrition diets. However, serum cholesterol did not increase after the renutrition period. We observed a significant decrease (P < 0.05) in the leukocyte counts in calorie-restricted mice in comparison with AD mice; after the renutrition period, the leukocyte count did not reach the values for the AD mice. CONCLUSION:This study suggests that a short-term change in diet with a relatively low body weight loss does not significantly affect leptin concentrations in our mouse model. However, the assayed milks could be effectively used as alternative milk sources for weight gain and for the improvement of other metabolic parameters. 10.1016/j.nut.2008.09.003
    Lemon detox diet reduced body fat, insulin resistance, and serum hs-CRP level without hematological changes in overweight Korean women. Kim Mi Joung,Hwang Jung Hyun,Ko Hyun Ji,Na Hye Bock,Kim Jung Hee Nutrition research (New York, N.Y.) The lemon detox program is a very low-calorie diet which consists of a mixture of organic maple and palm syrups, and lemon juice for abstinence period of 7 days. We hypothesized that the lemon detox program would reduce body weight, body fat mass, thus lowering insulin resistance and known risk factors of cardiovascular disease. We investigated anthropometric indices, insulin sensitivity, levels of serum adipokines, and inflammatory markers in overweight Korean women before and after clinical intervention trial. Eighty-four premenopausal women were randomly divided into 3 groups: a control group without diet restriction (Normal-C), a pair-fed placebo diet group (Positive-C), and a lemon detox diet group (Lemon-D). The intervention period was 11 days total: 7 days with the lemon detox juice or the placebo juice, and then 4 days with transitioning food. Changes in body weight, body mass index, percentage body fat, and waist-hip ratio were significantly greater in the Lemon-D and Positive-C groups compared to the Normal-C group. Serum insulin level, homeostasis model assessment insulin resistance scores, leptin, and adiponectin levels decreased in the Lemon-D and Positive-C groups. Serum high-sensitive C-reactive protein (hs-CRP) levels were also reduced only in the Lemon-D group. Hemoglobin and hematocrit levels remained stable in the Lemon-D group while they decreased in the Positive-C and Normal-C groups. Therefore, we suppose that the lemon detox program reduces body fat and insulin resistance through caloric restriction and might have a potential beneficial effect on risk factors for cardiovascular disease related to circulating hs-CRP reduction without hematological changes. 10.1016/j.nutres.2015.04.001
    [Relationship between perirenal adipose tissue neuropeptide Y and insulin resistance in nutritional transition model]. Wang Suxing,Li Fang,Wang Na,Lyu Caixia,Shao Weihua,Li Xiuqin,Li Shaobing Wei sheng yan jiu = Journal of hygiene research OBJECTIVE:To observe the changes of neuropeptide Y(NPY) expression in perirenal adipose tissue and its relationship with insulin resistance in the nutritional transition models of refeeding after calorie restriction. METHODS:SPF Male SD rats, aged 8 weeks, were randomly divided into normal chow group and refeeding with normal chow after calorie restriction for 4 weeks group. NPY gene expression in perirenal adipose tissue were detected by real-time quantitative PCR at the end of 4 and 12 weeks, along with fasting plasma glucose, fasting serum lisulin, free fatty acids and average glucose infusion rate(GIR_(60-120)) of hyperinsulinemic-euglycemic clamp test for 60-120 minutes. NPY gene mRNA expression in perirenal adipose tissue was detected by real-time quantitative PCR. And the relationship between NPY gene expression and insulin resistance was detected by Spearman correlation analysis. RESULTS:The expression level of NPY gene in perirenal adipose tissue in caloric restriction for 4 weeks group was significantly increased by calorie restriction(P&lt;0. 01). After refeeding, the expression level of NPY gene in refeeding with normal group was still slightly increased, which was significantly higher than that in normal group at the end of the experiment(P&lt;0. 01). The levels of fasting plasma glucose and fasting insulin in caloric restriction for 4 weeks group decreased slightly, GIR_(60-120) increased slightly, but there were no statistical differences compared with normal group(P&gt;0. 05), but free fatty acid levels increased significantly(P&lt;0. 01). After refeeding, the levels of fasting insulin, free fatty acid in refeeding with normal group increased significantly, GIR_(60-120) decreased evidently(P&lt;0. 01), but the changes of fasting blood glucose were not obvious. The result of stepwise regression showed that the expression level of NPY gene in perirenal adipose tissue was closely related to GIR_(60-120) and fasting insulin, with R values of-0. 816 and 0. 789 respectively(R~2=0. 892, P&lt;0. 01). The result of correlation analysis showed that in the 4-week group, the mRNA expression level of NPY gene in perirenal adipose tissue was closely related to GIR_( 60-120)、fasting insulin and free fatty acid, with R values of-0. 765, 0. 716 and 0. 657 respectively(P&lt;0. 01). In the 12 week group, the mRNA expression level of NPY gene in perirenal adipose tissue was closely related to GIR_(60-120), fasting insulin and free fatty acid, with R values of-0. 853, 0. 622 and 0. 608 respectively(P&lt;0. 01). CONCLUSION:The mRNA expression of NPY gene in perirenal adipose tissue was closely related to indicators of insulin resistance. It is an important factor affecting insulin sensitivity. 10.19813/j.cnki.weishengyanjiu.2020.04.010
    Short-term low-calorie diet remodels skeletal muscle lipid profile and metabolic gene expression in obese adults. Nylén Carolina,Lundell Leonidas S,Massart Julie,Zierath Juleen R,Näslund Erik American journal of physiology. Endocrinology and metabolism Diet intervention in obese adults is the first strategy to induce weight loss and improve insulin sensitivity. We hypothesized that improvements in insulin sensitivity after weight loss from a short-term dietary intervention tracks with alterations in expression of metabolic genes and abundance of specific lipid species. Eight obese, insulin-resistant, nondiabetic adults were recruited to participate in a 3-wk low-calorie diet intervention cohort study (1,000 kcal/day). Fasting blood samples and vastus lateralis skeletal muscle biopsies were obtained before and after the dietary intervention. Clinical chemistry and measures of insulin sensitivity were determined. Unbiased microarray gene expression and targeted lipidomic analysis of skeletal muscle was performed. Body weight was reduced, insulin sensitivity [measured by homeostatic model assessment of insulin resistance, (HOMA-IR)] was enhanced, and serum insulin concentration and blood lipid (triglyceride, cholesterol, LDL, and HDL) levels were improved after dietary intervention. Gene set enrichment analysis of skeletal muscle revealed that biosynthesis of unsaturated fatty acid was among the most enriched pathways identified after dietary intervention. mRNA expression of PDK4 and MLYCD increased, while SCD1 decreased in skeletal muscle after dietary intervention. Dietary intervention altered the intramuscular lipid profile of skeletal muscle, with changes in content of phosphatidylcholine and triglyceride species among the pronounced. Short-term diet intervention and weight loss in obese adults alters metabolic gene expression and reduces specific phosphatidylcholine and triglyceride species in skeletal muscle, concomitant with improvements in clinical outcomes and enhanced insulin sensitivity. 10.1152/ajpendo.00253.2018
    A Data Integration Multi-Omics Approach to Study Calorie Restriction-Induced Changes in Insulin Sensitivity. Dao Maria Carlota,Sokolovska Nataliya,Brazeilles Rémi,Affeldt Séverine,Pelloux Véronique,Prifti Edi,Chilloux Julien,Verger Eric O,Kayser Brandon D,Aron-Wisnewsky Judith,Ichou Farid,Pujos-Guillot Estelle,Hoyles Lesley,Juste Catherine,Doré Joël,Dumas Marc-Emmanuel,Rizkalla Salwa W,Holmes Bridget A,Zucker Jean-Daniel,Clément Karine, Frontiers in physiology The mechanisms responsible for calorie restriction (CR)-induced improvement in insulin sensitivity (IS) have not been fully elucidated. Greater insight can be achieved through deep biological phenotyping of subjects undergoing CR, and integration of big data. An integrative approach was applied to investigate associations between change in IS and factors from host, microbiota, and lifestyle after a 6-week CR period in 27 overweight or obese adults (ClinicalTrials.gov: NCT01314690). Partial least squares regression was used to determine associations of change (week 6 - baseline) between IS markers and lifestyle factors (diet and physical activity), subcutaneous adipose tissue (sAT) gene expression, metabolomics of serum, urine and feces, and gut microbiota composition. ScaleNet, a network learning approach based on spectral consensus strategy (SCS, developed by us) was used for reconstruction of biological networks. A spectrum of variables from lifestyle factors (10 nutrients), gut microbiota (10 metagenomics species), and host multi-omics (metabolic features: 84 from serum, 73 from urine, and 131 from feces; and 257 sAT gene probes) most associated with IS were identified. Biological network reconstruction using SCS, highlighted links between changes in IS, serum branched chain amino acids, sAT genes involved in endoplasmic reticulum stress and ubiquitination, and gut metagenomic species (MGS). Linear regression analysis to model how changes of select variables over the CR period contribute to changes in IS, showed greatest contributions from gut MGS and fiber intake. This work has enhanced previous knowledge on links between host glucose homeostasis, lifestyle factors and the gut microbiota, and has identified potential biomarkers that may be used in future studies to predict and improve individual response to weight-loss interventions. Furthermore, this is the first study showing integration of the wide range of data presented herein, identifying 115 variables of interest with respect to IS from the initial input, consisting of 9,986 variables. clinicaltrials.gov (NCT01314690). 10.3389/fphys.2018.01958
    Effects of timing of food intake and fat/carbohydrate ratio on insulin sensitivity and preconditioning against renal ischemia reperfusion injury by calorie restriction. Reynolds Justin S,Peng Wei,Chu Timothy,Mitchell James R Nutrition and healthy aging BACKGROUND:Dietary restriction (DR) improves lifespan, metabolic fitness and resilience in many organisms, but the role of dietary macronutrient composition and timing of food intake in specific benefits remains unclear. OBJECTIVE:We sought to compare the effects of two isocaloric DR regimes differing in the timing of food intake - every other day (EOD) fasting/feeding vs. daily calorie restriction (CR) - at two different fat/carbohydrate ratios on two well-established DR benefits, improved glucose homeostasis and protection from renal ischemia reperfusion injury in mice. We hypothesized that both EOD fasting and isocaloric CR would result in similar improvements in glucose homeostasis and stress resistance independent of macronutrient composition. METHODS:Six groups of mice were fed either semi-purified low-fat diet (LFD, 10% calories from fat) or high-fat diet (HFD, 60% calories from fat) and randomized into one of three dietary regimens: 1) (AL), 2) EOD feeding/fasting, or 3) pair-fed daily to the average daily EOD intake within LFD or HFD feeding group resulting in daily CR. After 6 weeks, the following assessments were made: fasting blood glucose, glucose and insulin tolerance, and resistance to bilateral renal ischemia reperfusion injury using serum urea as a marker of renal function. Within the EOD group, the effects of prior day feeding (EOD vs. EOD) were also assessed. RESULTS:EOD mice ate ∼20-25% less food over time than AL mice on the corresponding LFD or HFD. EOD and CR mice displayed changes in body weight, fasting blood glucose levels and glucose tolerance commensurate with total calorie intake. No significant differences were observed in circulating IGF-1 levels. Insulin sensitivity improved independent of fat/carbohydrate ratio on daily CR and EOD regimens, but not EOD. HFD increased susceptibility to renal ischemia reperfusion in AL mice, while CR and EOD regimens gave significant protection independent of dietary fat content or fed or fasted day in the EOD group. CONCLUSIONS:Reduced food intake protects mice against renal ischemia reperfusion injury within 6 weeks independent of timing of food intake (CR, EOD, EOD) or fat content of diet (10% vs. 60%). Neither circulating IGF-1 levels (unchanged) nor whole-body insulin sensitivity (improved upon daily CR and EOD but not EOD) correlated with protection, so are unlikely to be involved mechanistically. 10.3233/NHA-180044
    Subcutaneous adipose tissue cytokine production is not responsible for the restoration of systemic inflammation markers during weight loss. Salas-Salvadó J,Bulló M,García-Lorda P,Figueredo R,Del Castillo D,Bonada A,Balanzà R International journal of obesity (2005) CONTEXT:It has been suggested that weight loss can improve systemic inflammation associated with obesity by decreasing the adipose production of pro-inflammatory cytokines. This suggestion, however, remains controversial. OBJECTIVE:To analyse the effect of weight loss on peripheral inflammatory markers and subcutaneous adipocytokine production. DESIGN:Patients were studied at baseline, at the end of the weight loss period, and after 2 weeks of weight stabilisation. SUBJECTS:Nineteen morbid obese non-diabetic patients and 20 lean control subjects. INTERVENTION:During the weight loss period patients followed a 6-week low-calorie diet. MEASUREMENTS:Plasma levels of inflammatory markers, maximal in vitro whole-blood cytokine production, subcutaneous adipose tissue expression and content of several cytokines. RESULTS:Obese subjects had higher circulating levels of C reactive protein (CRP), serum amyloid A (SAA), interleukin IL-6, IL-1 and soluble tumor necrosis factor receptors (sTNFR). Weight loss was associated with a significant decrease in CRP, SAA, leucocytes and plasma IL-6. Maximal in vitro cytokine production of IL-1 and sTNFR1 increased during this period. Weight loss did not induce significant changes in the adipose concentrations of IL-6, IL-1 or sTNF-receptors. However, adipose expression of IL-6, IL-1, TNFalpha, membrane cofactor protein-1 and adiponectin increased at the end of the weight loss period. During weight maintenance, circulating inflammatory parameters increased and in some cases returned to baseline. CONCLUSIONS:A low-calorie diet is associated with an improvement in the systemic inflammatory status. This seems to be due to energy restriction rather than to adipose mass loss, since inflammatory levels return to baseline soon after weight stabilisation. Furthermore, a negative energy balance and fat mobilisation are associated with increased subcutaneous cytokine adipose expression. 10.1038/sj.ijo.0803348
    Effect of 6-month calorie restriction and exercise on serum and liver lipids and markers of liver function. Larson-Meyer D Enette,Newcomer Bradley R,Heilbronn Leonie K,Volaufova Julia,Smith Steven R,Alfonso Anthony J,Lefevre Michael,Rood Jennifer C,Williamson Donald A,Ravussin Eric, Obesity (Silver Spring, Md.) OBJECTIVE:Nonalcoholic fatty liver disease (NAFLD) and its association with insulin resistance are increasingly recognized as major health burdens. The main objectives of this study were to assess the relation between liver lipid content and serum lipids, markers of liver function and inflammation in healthy overweight subjects, and to determine whether caloric restriction (CR) (which improves insulin resistance) reduces liver lipids in association with these same measures. METHODS AND PROCEDURES:Forty-six white and black overweight men and women (BMI = 24.7-31.3 kg/m(2)) were randomized to "control (CO)" = 100% energy requirements; "CR" = 25%; "caloric restriction and increased structured exercise (CR+EX)"= 12.5% CR + 12.5% increase in energy expenditure through exercise; or "low-calorie diet (LCD)" = 15% weight loss by liquid diet followed by weight-maintenance, for 6 months. Liver lipid content was assessed by magnetic resonance spectroscopy (MRS) and computed tomography (CT). Lipid concentrations, markers of liver function (alanine aminotransferase (ALT), alkaline phosphatase (ALK)), and whole-body inflammation (tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), high-sensitivity C-reactive protein (hsCRP)) were measured in fasting blood. RESULTS:At baseline, increased liver lipid content (by MRS) correlated (P < 0.05) with elevated fasting triglyceride (r = 0.52), ALT (r = 0.42), and hsCRP (r = 0.33) concentrations after adjusting for sex, race, and alcohol consumption. With CR, liver lipid content was significantly lowered by CR, CR+EX, and LCD (detected by MRS only). The reduction in liver lipid content, however, was not significantly correlated with the reduction in triglycerides (r = 0.26; P = 0.11) or with the changes in ALT, high-density lipoprotein (HDL)-cholesterol, or markers of whole-body inflammation. DISCUSSION:CR may be beneficial for reducing liver lipid and lowering triglycerides in overweight subjects without known NAFLD. 10.1038/oby.2008.201
    Weight loss-dependent and -independent effects of moderate calorie restriction on endothelial cell markers in obesity. Korybalska K,Luczak J,Swora-Cwynar E,Kanikowska A,Czepulis N,Kanikowska D,Skalisz H,Breborowicz A,Grzymislawski M,Witowski J Journal of physiology and pharmacology : an official journal of the Polish Physiological Society Endothelial cell dysfunction in obesity can be reduced by calorie restriction (CR), however it is unclear whether this benefit requires a concomitant weight loss or is it simply related to the reduced calorie intake per se. In our study serum was drawn from 41 obese women who were undergoing an 8-week dietary intervention with 15 - 30% energy deficit, and from 48 age- and sex-matched controls of normal weight. Serum was analysed for biomarkers of endothelial cell function, oxidative stress and inflammation. Compared with non-obese individuals, the obese patients had lower serum levels of nitric oxide (NO), adiponectin, and decreased serum antioxidant status. They also had significantly higher levels of adhesive molecules, thrombomodulin (TM), von Wilebrand factor (vWF), asymmetric dimethylarginine (ADMA), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and leptin. To further characterize the effect of moderate CR, the patients were ranked into two comparable groups according to the extent of weight loss - below and above the median (-5.8 kg). A moderate dietary intervention did not correct adiponectin, antioxidant status, vWF, TM, and plasminogen activator inhibitor-1 (PAI-1) but ameliorated changes in other parameters. Only changes in NO and - to a lesser degree - in sE-selectin showed a clear relationship with the magnitude of weight reduction. By contrast, a beneficial reduction in TNF-α occurred equally in patients who lost more or less weight after caloric restriction. We concluded that moderate calorie restriction could still improve several parameters of endothelial cell function irrespective of whether it was accompanied by changes in body mass. However, a significant improvement in nitric oxide, a key mediator of endothelial well-being, requires a substantial reduction in body weight.
    Pigmented rice bran and plant sterol combination reduces serum lipids in overweight and obese adults. Hongu Nobuko,Kitts David D,Zawistowski Jerzy,Dossett Cynthia M,Kopeć Aneta,Pope Benjamin T,Buchowski Maciej S Journal of the American College of Nutrition OBJECTIVE:This study investigated the dietary effect of including pigmented rice bran with or without plant sterols on lipid profiles during energy restriction-induced weight loss in overweight and obese adults not taking cholesterol-lowering medication. In addition, the study examined the effect of intervention on biomarkers of oxidative stress and inflammation. METHODS:A group of 24 overweight and obese adults (age: 43 ± 6 years, body mass index 32 ± 1 kg/m(2), 18 females) were randomized to a 25% calorie-restricted diet containing either pigmented rice bran (RB) or the RB with addition of plant sterols (RB+PS) snack bars for 8 weeks. The individualized nutrient-balanced diet contained ∼70% of daily energy needs assessed from indirect calorimetry measured resting energy expenditure (EE) and physical activity-related EE assessed using accelerometry. Anthropometrics, blood pressure, blood lipids, glucose, urinary F2-isoprostanes, C-reactive protein, insulin, and leptin were measured at baseline and after 8 weeks of intervention. RESULTS:Participants lost approximately 4.7 ± 2.2 kg (p < 0.001). Weight loss was not significant between the RB+PS and RB group (p = 0.056). Changes in body fat corresponded to changes in body weight. Average decrease in total cholesterol was significantly higher in the RB+PS group than in the RB group (difference 36 ± 25 g/dL vs 7 ± 16 g/dL; p = 0.044). A similar pattern was observed for the decrease in low-density lipoprotein (LDL) cholesterol (difference 22.3 ± 25.2 g/dL vs 4.4 ± 18.9 g/dL; p = 0.062). Changes in systolic blood pressure, serum levels of leptin, and F2-isoprostanes were significant between baseline values and after 8 weeks on the diet in both groups (p < 0.05) but did not differ between the 2 groups. CONCLUSIONS:A nutrient-balanced and energy-restricted diet supplemented with rice bran and plant sterols resulted in a significant decrease in total and LDL cholesterol in overweight and obese adults. 10.1080/07315724.2013.869772
    Markers of adipose tissue inflammation are transiently elevated during intermittent fasting in women who are overweight or obese. Liu Bo,Hutchison Amy T,Thompson Campbell H,Lange Kylie,Heilbronn Leonie K Obesity research & clinical practice OBJECTIVE:This study compared the effects of daily calorie restriction (DR) versus intermittent fasting (IF) on markers of inflammation and extracellular matrix deposition in adipose tissue and skeletal muscle in a controlled feeding trial in women with overweight or obesity. METHODS:Women (N = 76) were randomised to one of three diets and provided with all foods at 100% (IF100) or 70% (IF70 and DR70) of calculated energy requirements for 8 weeks. IF groups ate breakfast prior to fasting for 24-h on 3 non-consecutive days/week. Weight, body composition, serum non-esterified fatty acids (NEFA), tumour necrosis factor-alpha (TNFα), interleukin-6 (IL-6), interleukin-10 (IL-10), M1- and M2-macrophage markers by qPCR and immunohistochemistry in adipose tissue and skeletal muscle were measured following a 12-h overnight fast (fed day, all groups) and a 24-h fast (IF groups only). RESULTS:IF70 resulted in greater weight and fat losses and reductions in serum NEFA versus DR70 and IF100 (P < 0.05) after fed days. Markers of inflammation in serum (TNFα, IL6 and IL10), subcutaneous adipose tissue and skeletal muscle (CD68, CD40 and CD163) were unchanged by DR or IF after fed days. After fasting, NEFA, M1-macrophages (CD40) in adipose tissue, and M2-macrophages (CD163) in muscle were increased in IF70 and IF100 (all P < 0.05) and the changes in NEFA and mRNA of pan-macrophage marker CD68 in adipose tissue were positively correlated (r = 0.56, P = 0.002). CONCLUSIONS:Unlike caloric restriction, IF transiently elevated markers of macrophage infiltration in adipose tissue and skeletal muscle, possibly in response to marked increases in adipose tissue lipolysis. 10.1016/j.orcp.2019.07.001
    Genetic variation at the perilipin locus is associated with changes in serum free fatty acids and abdominal fat following mild weight loss. Jang Y,Kim O Y,Lee J H,Koh S J,Chae J S,Kim J Y,Park S,Cho H,Lee J E,Ordovas J M International journal of obesity (2005) OBJECTIVE:Perilipin (PLIN) is a class of protein-coating lipid droplets in adipocytes. We aimed to examine the association between common single-nucleotide polymorphisms (SNPs) at PLIN locus with circulating free fatty acid (FFA) and abdominal fat distribution in response to weight loss. METHODS:Non-diabetic/overweight-obese Koreans (n=177) participated in a 12-week calorie restriction (-300kcal/day) program. Seven SNPs (6209T>C, 10076C>G, 10171A>T, 11482G>A, 13042A>G, 13048C>T and 14995A>T), abdominal fat areas (visceral/subcutaneous fat areas at 1st lumbar and 4th lumbar levels), serum lipids, glucose, insulin, FFA, oxidized low-density lipoprotein (LDL) and urinary 8-epi-prostaglandin F(2alpha) (PGF(2alpha)) were examined. RESULTS:Single-nucleotide polymorphisms 10076C>G/10171A>T showed the strongest positive linkage disequilibrium (LD) (D'=0.923, R (2)=0.839, P<0.001) and SNPs11482G>A/14995A>T showed moderate positive LD (D'=0.824, R (2)=0.578, P<0.001). Calorie restriction induced 4.6% weight loss with significant abdominal fat reduction. In response to weight loss, subjects with nCA/nCA haplotypes at SNPs 10076C>G/10171A>T showed greater reduction in FFA levels than those with CA/CA haplotype (CA/CA: C/C at SNP 10076 and A/A at SNP 10171, nCA: non-CA haplotype carrier). On the other hand, subjects with nGA/nGA haplotype at SNPs 11482G>A/14995A>T had increased FFA levels with a rapid loss in abdominal fat, whereas GA/GA haplotype carriers had reduction in FFA levels. These results still remained significant after adjusting for age, gender and BMI. Prostaglandin F(2alpha) and oxidized LDL were also more reduced in GA/GA haplotype carriers than in nGA haplotype carriers. This effect remained significant after adjusting for baseline level, age, gender and BMI. Paradoxically, nGA haplotype carriers had increased levels of urinary PGF(2alpha) after weight reduction. CONCLUSION:Fasting plasma FFA changes following a modest weight loss in overweight-obese subjects are influenced by the genetic variability at the PLIN locus. Furthermore, circulating FFA changes rather than body fat itself may determine changes in lipid peroxides such as urinary PGF(2alpha) and oxidized LDL. 10.1038/sj.ijo.0803312
    [Changes in serum and adipose tissue fatty acid composition after low calorie diet with respect to dietary fat content in obese]. Vecka M,Richterová B,Zák A,Tvrzická E,Srámková P,Stanková B,Klimcáková E,Stich V Casopis lekaru ceskych BACKGROUND:Recently, a new attention has been paid to beneficial effects of high-fat diet on the body weight reduction and metabolic profile in obese subjects. In this study we compared the effects of two hypocaloric diets with different proportion of fat on fatty acid composition (FA) in blood and adipose tissue (AT). METHODS AND RESULTS:Forty-four obese subjects were submitted to 10 weeks' low-calorie diet. Subjects were randomized into low-fat diet (LFD) (20-25% of energy content) and high-fat diet groups (HFD) (40-45%). Before and at the end of the intervention, samples of blood and subcutaneous AT were taken for the analysis of fatty acid composition. The diet-induced body weight and fat mass reduction were not different between the two diets. Plasma triacylglycerols (TAG) were reduced during HFD only. Both diets reduced proportion of n-3 polyunsaturated fatty acids in AT and of saturated fatty acid in blood TAG, with no difference between the diets. HFD induced a higher increase of monounsaturated fatty acids in blood TAG. No other diet-induced changes were found in proportion of major classes of fatty acids. In respect to individual fatty acids, the diets induced a number of changes in AT and blood, the changes, however, not being different between the diets. CONCLUSION:Hypocaloric diets induce a number of changes in fatty acid composition in blood and adipose tissue, with little differences in respect to the proportion of fat in the diet. The results suggest the diet-induced changes in fatty acid composition are controlled by the calorie deficit of the diet and the proportion of dietary fat plays a minor role.
    Effect of weight loss on circulating fatty acid profiles in overweight subjects with high visceral fat area: a 12-week randomized controlled trial. Lee Young Ju,Lee Ayoung,Yoo Hye Jin,Kim Minjoo,Kim Minkyung,Jee Sun Ha,Shin Dong Yeob,Lee Jong Ho Nutrition journal BACKGROUND:Significant associations between visceral fat and alterations in plasma fatty acids have been identified in overweight individuals. However, there are scant data regarding the relationships of the visceral fat area (VFA) with the plasma fatty acid profiles and desaturase activities following weight loss. We investigated the effect of weight loss with mild calorie restriction on the circulating fatty acid profiles and desaturase activities in nondiabetic overweight subjects with high VFA. METHODS:Eighty overweight subjects with high VFA (L4 VFA ≥100 cm) were randomized into the 12-week mild-calorie-restriction (300 kcal/day) or control groups. RESULTS:Comparison of the percent of body weight changes between groups revealed that the weight-loss group had greater reductions in body weight. The VFA decreased by 17.7 cm from baseline in the weight-loss group (P < 0.001). At follow-up, the weight-loss group showed greater reductions in serum triglycerides, insulin, and HOMA-IR than the control group. Significantly greater reductions in total saturated fatty acids, palmitic acid, stearic acid, total monounsaturated fatty acids, palmitoleic acid, oleic acid, eicosadienoic acid, and dihomo-γ-linolenic acid levels were detected in the weight-loss group compared with the control group after adjusting for baseline values. Following weight loss, C16 Δ9-desaturase activity was significantly decreased and Δ5-desaturase activity was significantly increased, and the changes were greater in the weight-loss group than in the control group. CONCLUSIONS:The results suggest that mild weight loss improves abdominal obesity, overall fatty acid profiles, and desaturase activities; therefore, mild calorie restriction has potential health benefits related to obesity-related diseases in overweight subjects with high VFA. TRIAL REGISTRATION:NCT02992639. Retrospectively registered 11 December 2016. 10.1186/s12937-018-0323-4
    The effect of royal jelly and tocotrienol-rich fraction along with calorie restriction on hypothalamic endoplasmic reticulum stress and adipose tissue inflammation in diet-induced obese rats. Irandoost Pardis,Mesri Alamdari Naimeh,Saidpour Atoosa,Shidfar Farzad,Farsi Farnaz,Asghari Jafarabadi Mohammad,Alivand Mohammad Reza,Vafa Mohammadreza BMC research notes OBJECTIVES:Endoplasmic reticulum (ER) stress causes adipose tissue dysfunction and chronic inflammation in obesity. Royal jelly (RJ) and tocotrienol-rich fraction (TRF) are reported to ameliorate inflammation. However, the improving effects of RJ and TRF on inflammation from ER stress modulating view have not been assessed so far. Hence, we investigated the effect of RJ and TRF on ER stress and some adipose tissue-derived inflammatory markers in the high-fat diet (HFD)-induced obesity. Wistar obese rats randomly allocated into 5 groups: HFD, calorie restriction diet (CRD), RJ + CRD, TRF + CRD, RJ + TRF + CRD. After 8-week intervention, adipose tissues and hypothalamus were dissected and serum was collected. RESULTS:RJ reduced glucose-regulated protein-78 (GRP78) expression as ER stress indicator in WAT and hypothalamus compared to CRD. Besides, RJ diminished the expression of inflammatory markers in white adipose tissue (WAT) and also decreased the serum concentration of them. TRF reduced inflammatory markers in the serum without remarkable effects on ER stress. Overall, RJ has protective effect against adipose tissue dysfunction and inflammation then suggested as a therapeutic approach to reduce some obesity-related complications. The impact of TRF in this regard is lower than RJ and limited to systemic inflammation improvement without remarkable changes in adipose tissue inflammation. 10.1186/s13104-020-05258-0
    The effects of spinach-derived thylakoid supplementation in combination with calorie restriction on anthropometric parameters and metabolic profiles in obese women with polycystic ovary syndrome: a randomized, double-blind, placebo-controlled clinical trial. Tabrizi Fatemeh Pourteymour Fard,Farhangi Mahdieh Abbasalizad,Vaezi Maryam,Hemmati Salar Nutrition journal BACKGROUND:There is a promising outlook regarding the potential effect of spinach-derived thylakoids in the management of obesity and its associated metabolic disturbances. This research aimed to evaluate the effects of spinach-derived thylakoids supplementation combined with a calorie-restricted diet on anthropometric and metabolic profiles in obese women with the polycystic ovary syndrome (PCOS). METHODS:In a 12-week double-blind placebo-controlled randomized clinical trial, 48 females with obesity and PCOS were randomly allocated into either intervention (5 g/day thylakoid) or placebo (5 g/day cornstarch) groups along with calorie-restricted diets. Anthropometric measures, physical activity levels, dietary intakes, insulin resistance markers, as well as serum levels of insulin, fasting blood glucose (FBG), non-esterified fatty acids (NEFA), and sex hormones including dehydroepiandrosterone sulfate (DHEAS), follicle-stimulating hormone (FSH), luteinizing hormone (LH), sex hormone-binding globulin (SHBG), and free androgen index (FAI) were evaluated pre-and post-intervention. RESULTS:After the 12-week intervention, there were significant decreases in weight (- 6.97 ± 0.52 vs. -3.19 ± 0.72 kg; P < 0.001), waist circumference (- 7.78 ± 2.50 vs. -3.73 ± 1.40 cm; P < 0.001), fat mass (- 5.19 ± 0.53 vs. -1.36 ± 0.39 kg; P < 0.001), and insulin levels (- 5.40 ± 1.86 vs. -1.19 ± 0.85 μU/mL; P < 0.001) in the spinach-derived thylakoid group compared to the placebo group. Furthermore, insulin resistance markers and serum levels of testosterone decreased significantly in the thylakoid group compared to the placebo group (P < 0.05). The changes in other parameters did not show significant differences between the two groups. CONCLUSIONS:Spinach-derived thylakoid supplementation resulted in more favorable improvements in anthropometric indices and insulin sensitivity compared to the calorie restriction alone. TRIAL REGISTRATION:The study was approved by the Ethics Committee of Research Vice-chancellor of Tabriz University of Medical Sciences, Tabriz, Iran, and was registered in the Iranian Registry of Clinical Trials (registration ID: IRCT20140907019082N9 ). 10.1186/s12937-020-00601-4
    Obesity-induced taste dysfunction, and its implications for dietary intake. Harnischfeger Fiona,Dando Robin International journal of obesity (2005) The incidence of obesity has dramatically increased in recent years, and poses a public health challenge for which an effective and scalable intervention strategy is yet to be found. Our food choices are one of the primary drivers of obesity, where the overconsumption of energy from foods high in fat and sugar can be particularly problematic. Unfortunately, these same foods also tend to be highly palatable. We select foods more on their sensory properties than on any other factor, such as price, convenience, or healthfulness. Previous evidence from human sensory studies has suggested a depressed sense of taste in panelists with obesity. Evidence from animal models also demonstrates a clear deficiency in taste buds occurring with obesity, suggesting that damage to the taste system may result from an obese state. In this review only taste, as opposed to smell, will be examined. Here we seek to bring together evidence from a diverse array of human and animal studies into taste response, dietary intake, and physiology, to better understand changes in taste with obesity, with the goal of understanding whether taste may provide a novel target for intervention in the treatment of obesity. 10.1038/s41366-021-00855-w
    Effect of Synbiotic Supplementation in a Very-Low-Calorie Ketogenic Diet on Weight Loss Achievement and Gut Microbiota: A Randomized Controlled Pilot Study. Gutiérrez-Repiso Carolina,Hernández-García Carmen,García-Almeida José Manuel,Bellido Diego,Martín-Núñez Gracia María,Sánchez-Alcoholado Lidia,Alcaide-Torres Juan,Sajoux Ignacio,Tinahones Francisco J,Moreno-Indias Isabel Molecular nutrition & food research SCOPE:Little is known about the changes that a very-low-calorie ketogenic diet (VLCKD) produces in gut microbiota or the effect of synbiotics during the diet. The aim of this study is to evaluate changes in gut microbiota produced by a VLCKD and synbiotic supplementation. METHODS AND RESULTS:A randomized, single-blind, parallel-design trial is conducted in 33 obese patients who follow a weight-loss program (PnK-Method) that include a VLCKD followed by a low-calorie diet (LCD). Subjects are randomly allocated to three groups: one supplemented with synbiotics, a second group supplemented with a placebo during the VLCKD and synbiotics during the LCD phase, and a control group given a placebo. Although symbiotic administration do not produce an effect on microbial diversity, an increase in short-chain fatty aciding producing bacteria and anti-inflammatory mediator signals such as Odoribacter and Lachnospira is shown. The administration of Bifidobacterium animalis subsp. lactis and prebiotics fiber during the LCD is significantly associated with the percentage of weight loss and change in glucose, C-reactive protein and lipopolysaccharide-binding protein. CONCLUSIONS:VLCKD produces important changes in gut microbiota. The administration of synbiotics during VLCKD can improve weight loss through the amelioration of inflammation, which may be mediated by the gut microbiota. 10.1002/mnfr.201900167
    The Low-Carbohydrate Diet: Short-Term Metabolic Efficacy Versus Longer-Term Limitations. Barber Thomas M,Hanson Petra,Kabisch Stefan,Pfeiffer Andreas F H,Weickert Martin O Nutrients BACKGROUND:Diets have been a central component of lifestyle modification for decades. The Low-Carbohydrate Diet (LCD), originally conceived as a treatment strategy for intractable epilepsy (due to its association with ketogenesis), became popular in the 1970s and since then has risen to prominence as a weight loss strategy. OBJECTIVE:To explore the efficacy, limitations and potential safety concerns of the LCD. DATA SOURCES:We performed a narrative review, based on relevant articles written in English from a Pubmed search, using the terms 'low carbohydrate diet and metabolic health'. RESULTS:Evidence supports the efficacy of the LCD in the short-term (up to 6-months) for reduction in fat mass and remission of Type 2 Diabetes Mellitus (T2D). However, the longer-term efficacy of the LCD is disappointing, with diminishment of weight loss potential and metabolic benefits of the LCD beyond 6-months of its adoption. Furthermore, practical limitations of the LCD include the associated restriction of food choices that restrict the acceptability of the LCD for the individual, particularly over the longer term. There are also safety concerns of the LCD that stem from nutritional imbalances (with a relative excess of dietary fat and protein intake with associated dyslipidaemia and increased risk of insulin resistance and T2D development) and ketotic effects. Finally, the LCD often results in a reduction in dietary fibre intake, with potentially serious adverse consequences for overall health and the gut microbiota. CONCLUSIONS:Although widely adopted, the LCD usually has short-lived metabolic benefits, with limited efficacy and practicality over the longer term. Dietary modification needs tailoring to the individual, with careful a priori assessments of food preferences to ensure acceptability and adherence over the longer term, with avoidance of dietary imbalances and optimization of dietary fibre intake (primarily from plant-based fruit and vegetables), and with a posteriori assessments of the highly individual responses to the LCD. Finally, we need to change our view of diets from simply an excipient for weight loss to an essential component of a healthy lifestyle. 10.3390/nu13041187