Weight regain after a diet-induced loss is predicted by higher baseline leptin and lower ghrelin plasma levels

CONTEXT: Appetite-related hormones may play an important role in weight regain after obesity therapy. OBJECTIVE: Our objective was to investigate the potential involvement of ghrelin, leptin, and insulin plasma levels in weight regain after a therapeutic hypocaloric diet. DESIGN: A group of obese/overweight volunteers (49 women and 55 men; 35 ± 7 yr; 30.7 ± 2.4 kg/m(2)) followed an 8-wk hypocaloric diet (-30% energy expenditure) and were evaluated again 32 wk after treatment. Body weight as well as plasma fasting ghrelin, leptin, and insulin concentrations were measured at three points (wk 0, 8, and 32). RESULTS: After the 8-wk hypocaloric diet, the average weight loss was -5.0 ± 2.2% (P < 0.001). Plasma leptin and insulin concentrations decreased significantly, whereas ghrelin levels did not markedly change. In the group regaining more than 10% of the weight loss, leptin levels were higher (P < 0.01), whereas ghrelin levels were lower (P < 0.05). No differences were observed in insulin levels. Weight regain at wk 32 was negatively correlated with ghrelin and positively associated with leptin levels at baseline (wk 0) and endpoint (wk 8). These outcomes showed a gender-specific influence, being statistically significant among men for ghrelin and between women for leptin. Moreover, a decrease in ghrelin after an 8-wk hypocaloric diet was related to an increased risk for weight regain (odds ratio = 3.109; P = 0.008) whereas a greater reduction in leptin (odds ratio = 0.141; P = 0.001) was related to weight-loss maintenance. CONCLUSIONS: Subjects with higher plasma leptin and lower ghrelin levels at baseline could be more prone to regain lost weight, and hormones levels could be proposed as biomarkers for predicting obesity-treatment outcomes

Interplay of atherogenic factors, protein intake and betatrophin levels in obese–metabolic syndrome patients treated with hypocaloric diets

The present research evaluated circulating betatrophin levels in obese patients with metabolic syndrome features under energy-restricted weight-loss programs and in normal weight in order to stablish the putative interplay between the levels of this hormone, diet and metabolic risk factors linked to obesity and associated comorbidities

Higher baseline irisin concentrations are associated with greater reductions in glycemia and insulinemia after weight loss in obese subjects

Irisin is assumed to be a relevant link between muscle and weight maintenance as well as to mediate exercise benefits on health. The aim of this study was to assess the possible associations between irisin levels and glucose homeostasis in obese subjects with metabolic syndrome (MetS) following an energy-restricted treatment. Ninety-six adults with excessive body weight and MetS features underwent a hypocaloric dietary pattern for 8 weeks, within the RESMENA randomized controlled trial (www.clinicaltrials.gov; NCT01087086). After the intervention, dietary restriction significantly reduced body weight and evidenced a dietary-induced decrease in circulating levels of irisin in parallel with improvements on glucose homeostasis markers. Interestingly, participants with higher irisin values at baseline (above the median) showed a greater reduction on glucose (P=0.022) and insulin (P=0.021) concentrations as well as on the homeostasis model assessment index (P=0.008) and triglycerides (P=0.006) after the dietary intervention, compared with those presenting low-irisin baseline values (below the median). Interestingly, a positive correlation between irisin and carbohydrate intake was found at the end of the experimental period. In conclusion, irisin appears to be involved in glucose metabolism regulation after a dietary-induced weight loss

Effect of a Very-Low-Calorie Ketogenic Diet on Circulating Myokine Levels Compared with the Effect of Bariatric Surgery or a Low-Calorie Diet in Patients with Obesity

The preservation of muscle mass and muscle function after weight loss therapy is currently a considerable challenge in the fight against obesity. Muscle mass secretes proteins called myokines that have relevant functions in the regulation of metabolism and health. This study was aimed to evaluate whether a very low-calorie ketogenic (VLCK) diet may modulate myokine levels, in addition to changes in body composition, compared to a standard, balanced low-calorie (LC) diet or bariatric surgery in patients with obesity. Body composition, ketosis, insulin sensitivity and myokines were evaluated in 79 patients with overweight/obesity after a therapy to lose weight with a VLCK diet, a LC diet or bariatric surgery. The follow-up was 6 months. The weight loss therapies induced changes in myokine levels in association with changes in body composition and biochemical parameters. The effects on circulating myokine levels compared to those at baseline were stronger after the VLCK diet than LC diet or bariatric surgery. Differences reached statistical significance for IL-8, MMP2 and irisin. In conclusion, nutritional interventions or bariatric surgery to lose weight induces changes in circulating myokine levels, being this effect potentially most notable after following a VLCK diet

Association between circulating irisin levels and the promotion of insulin resistance during the weight maintenance period after a dietary weight-lowering program in obese patients

Objective. Weight regain is associated with the promotion of insulin resistance. The newly discovered myokine irisin, which was proposed to be involved in the management of insulin sensitivity, could play a role in this process. This study aimed to investigate the association between irisin and reduced insulin sensitivity induced by weight regain. Materials/Methods. Insulin sensitivity was evaluated according to the homeostasis model assessment of insulin resistance (HOMA-IR) in 136 obese patients who followed an eight-week hypocaloric diet (30% reduced energy expenditure) to lose weight and were re-evaluated four or six months after treatment. Irisin plasma levels, as well as the levels of leptin, adiponectin, ghrelin and TNF-α, were quantified in a sub-cohort (n=73) from the initially studied patients at baseline (T0), at the diet endpoint (T1) and after the follow-up period (T2). Results. After a successful dietary intervention to lose weight, 50% of the patients who regained the lost weight during the follow-up period were categorized as insulin resistant (HOMA-IR≥2.5) compared with only 25% of patients who maintained the weight loss (p=0.018). Importantly, in addition to the well-studied hormones leptin and adiponectin, irisin plasma levels were statistically associated with several risk factors for insulin resistance. Indeed, the increased risk of insulin resistance during the follow-up period was related to high irisin levels at baseline (odds ratio=4.2; p=0.039). Conclusions. Circulating irisin predicts the insulin resistance onset in association with weight regain. Therefore, irisin could be secreted as an adaptive response to counteract the deleterious effect of excess adiposity on glucose homeostasis

DNA methylation map in circulating leukocytes mirrors subcutaneous adipose tissue methylation pattern: a genome-wide analysis from non-obese and obese patients

The characterization of the epigenetic changes within the obesity-related adipose tissue will provide new insights to understand this metabolic disorder, but adipose tissue is not easy to sample in population-based studies. We aimed to evaluate the capacity of circulating leukocytes to reflect the adipose tissue-specific DNA methylation status of obesity susceptibility. DNA samples isolated from subcutaneous adipose tissue and circulating leukocytes were hybridized in the Infinium HumanMethylation 450 BeadChip. Data were compared between samples from obese (n = 45) and non-obese (n = 8-10) patients by Wilcoxon-rank test, unadjusted for cell type distributions. A global hypomethylation of the differentially methylated CpG sites (DMCpGs) was observed in the obese subcutaneous adipose tissue and leukocytes. The overlap analysis yielded a number of genes mapped by the common DMCpGs that were identified to reflect the obesity state in the leukocytes. Specifically, the methylation levels of FGFRL1, NCAPH2, PNKD and SMAD3 exhibited excellent and statistically significant efficiencies in the discrimination of obesity from non-obesity status (AUC > 0.80; p < 0.05) and a great correlation between both tissues. Therefore, the current study provided new and valuable DNA methylation biomarkers of obesity-related adipose tissue pathogenesis through peripheral blood analysis, an easily accessible and minimally invasive biological material instead of adipose tissue

Interplay of atherogenic factors, protein intake and betatrophin levels in obese–metabolic syndrome patients treated with hypocaloric diets

The present research evaluated circulating betatrophin levels in obese patients with metabolic syndrome features under energy-restricted weight-loss programs and in normal weight in order to stablish the putative interplay between the levels of this hormone, diet and metabolic risk factors linked to obesity and associated comorbidities

Plasma irisin depletion under energy restriction is associated with improvements in lipid profile in metabolic syndrome patients

Objective A recently discovered myokine, irisin, may have an important role in energy metabolism. This study aimed to evaluate the relationship between this hormone and the lipid profile of Metabolic Syndrome (MetS) patients following a hypocaloric diet. Design Ninety-three Caucasian adults (52 men/41 women) diagnosed with MetS followed an 8-week-long energy restricted programme (-30% of the energy requirements). Anthropometric measurements, biochemical markers and plasma irisin levels were analysed before and after the nutritional intervention. Results Global plasma irisin levels were significantly reduced at the end of the study (-72•0 ± 100•9 ng/mL, p < 0•001) accompanying the weight loss (-6•9%). The depletion of irisin significantly correlated with changes in some atherogenic-related variables: total cholesterol (B = 0•106, p = 0•018), total cholesterol/high density lipoprotein-cholesterol ratio (B = 0•002, p = 0•036), low density lipoprotein-cholesterol (B = 0•085, p = 0•037) and apolipoprotein B (B = 0•052, p = 0•002), independently of changes in body weight. Conclusions An association between the reduction of plasma irisin levels and the depletion of important lipid metabolism biomarkers was observed in patients with MetS undergoing an energy restricted programme

Higher baseline irisin concentrations are associated with greater reductions in glycemia and insulinemia after weight loss in obese subjects

Irisin is assumed to be a relevant link between muscle and weight maintenance as well as to mediate exercise benefits on health. The aim of this study was to assess the possible associations between irisin levels and glucose homeostasis in obese subjects with metabolic syndrome (MetS) following an energy-restricted treatment. Ninety-six adults with excessive body weight and MetS features underwent a hypocaloric dietary pattern for 8 weeks, within the RESMENA randomized controlled trial (www.clinicaltrials.gov; NCT01087086). After the intervention, dietary restriction significantly reduced body weight and evidenced a dietary-induced decrease in circulating levels of irisin in parallel with improvements on glucose homeostasis markers. Interestingly, participants with higher irisin values at baseline (above the median) showed a greater reduction on glucose (P=0.022) and insulin (P=0.021) concentrations as well as on the homeostasis model assessment index (P=0.008) and triglycerides (P=0.006) after the dietary intervention, compared with those presenting low-irisin baseline values (below the median). Interestingly, a positive correlation between irisin and carbohydrate intake was found at the end of the experimental period. In conclusion, irisin appears to be involved in glucose metabolism regulation after a dietary-induced weight loss

Association between circulating irisin levels and the promotion of insulin resistance during the weight maintenance period after a dietary weight-lowering program in obese patients

Objective. Weight regain is associated with the promotion of insulin resistance. The newly discovered myokine irisin, which was proposed to be involved in the management of insulin sensitivity, could play a role in this process. This study aimed to investigate the association between irisin and reduced insulin sensitivity induced by weight regain. Materials/Methods. Insulin sensitivity was evaluated according to the homeostasis model assessment of insulin resistance (HOMA-IR) in 136 obese patients who followed an eight-week hypocaloric diet (30% reduced energy expenditure) to lose weight and were re-evaluated four or six months after treatment. Irisin plasma levels, as well as the levels of leptin, adiponectin, ghrelin and TNF-α, were quantified in a sub-cohort (n=73) from the initially studied patients at baseline (T0), at the diet endpoint (T1) and after the follow-up period (T2). Results. After a successful dietary intervention to lose weight, 50% of the patients who regained the lost weight during the follow-up period were categorized as insulin resistant (HOMA-IR≥2.5) compared with only 25% of patients who maintained the weight loss (p=0.018). Importantly, in addition to the well-studied hormones leptin and adiponectin, irisin plasma levels were statistically associated with several risk factors for insulin resistance. Indeed, the increased risk of insulin resistance during the follow-up period was related to high irisin levels at baseline (odds ratio=4.2; p=0.039). Conclusions. Circulating irisin predicts the insulin resistance onset in association with weight regain. Therefore, irisin could be secreted as an adaptive response to counteract the deleterious effect of excess adiposity on glucose homeostasis