Liraglutide Activates Type 2 Deiodinase and Enhances ß3-Adrenergic-Induced Thermogenesis in Mouse Adipose Tissue.

Aims: Liraglutide is a long-acting glucagon-like peptide 1 (GLP-1) receptor agonist used as an anti-hyperglycemic agent in type 2 diabetes treatment and recently approved for obesity management. Weight loss is attributed to appetite suppression, but therapy may also increase energy expenditure. To further investigate the effect of GLP-1 signaling in thermogenic fat, we assessed adipose tissue oxygen consumption and type 2 deiodinase (D2) activity in mice treated with liraglutide, both basally and after ß3-adrenergic treatment. Methods: Male C57BL/6J mice were randomly assigned to receive liraglutide (400 µg/kg, n=12) or vehicle (n=12). After 16 days, mice in each group were co-treated with the selective ß3-adrenergic agonist CL316,243 (1 mg/kg, n=6) or vehicle (n=6) for 5 days. Adipose tissue depots were assessed for gene and protein expression, oxygen consumption, and D2 activity. Results: Liraglutide increased interscapular brown adipose tissue (iBAT) oxygen consumption and enhanced ß3-adrenergic-induced oxygen consumption in iBAT and inguinal white adipose tissue (ingWAT). These effects were accompanied by upregulation of UCP-1 protein levels in iBAT and ingWAT. Notably, liraglutide increased D2 activity without significantly upregulating its mRNA levels in iBAT and exhibited additive effects to ß3-adrenergic stimulation in inducing D2 activity in ingWAT. Conclusions: Liraglutide exhibits additive effects to those of ß3-adrenergic stimulation in thermogenic fat and increases D2 activity in BAT, implying that it may activate this adipose tissue depot by increasing intracellular thyroid activation, adding to the currently known mechanisms of GLP-1A-induced weight loss.

Effects of Prebiotic and Synbiotic Supplementation on Inflammatory Markers and Anthropometric Indices After Roux-en-Y Gastric Bypass: A Randomized, Triple-blind, Placebo-controlled Pilot Study.

BACKGROUND: Studies have shown that prebiotics and synbiotics modulate the intestinal microbiota and may have beneficial effects on the immune response and anthropometric indices; however, the impact of the use of these supplements after bariatric surgery is not yet known. GOALS: This study investigated the effects of prebiotic and synbiotic supplementation on inflammatory markers and anthropometric indices in individuals undergoing open Roux-en-Y gastric bypass (RYGB). STUDY: In this randomized, controlled, and triple-blind trial conducted as a pilot study, individuals undergoing RYGB (n=9) and healthy individuals (n=9) were supplemented with 6 g/d of placebo (maltodextrin), prebiotic (fructo-oligosaccharide, FOS), or synbiotic (FOS+Lactobacillus and Bifidobacteria strains) for 15 days. RESULTS: Interleukin-1ß, interleukin-6, tumor necrosis factor-α, C-reactive protein, albumin, and the C-reactive protein/albumin ratio showed no significant changes on comparison between groups after supplementation. The reduction in the body weight of patients undergoing RYGB was 53.8% higher in the prebiotic group compared with the placebo group (-0.7 kg, P=0.001), whereas the reduction in the BMI and the increase in the percentage of excess weight loss were higher in the placebo and the prebiotic groups compared with the synbiotic group (P<0.05). CONCLUSIONS: Supplementation of FOS increased weight loss, whereas both prebiotics and synbiotics were not able to promote significant changes in inflammatory markers, although in most analyses, there was a reduction in their absolute values. The use of FOS may represent a potential adjunct in the treatment of obesity.

A systematic review and meta-analysis of the prebiotics and synbiotics effects on glycaemia, insulin concentrations and lipid parameters in adult patients with overweight or obesity.

BACKGROUND & AIMS: Several studies have reported the effects of prebiotics and synbiotics supplementation in lipid profile and glucose homeostasis, however a pooled analysis of clinical trials that assessed these parameters has not been performed in overweight or obese individuals. The aim of this study was to evaluate the effects of prebiotics and synbiotics on plasma lipid profile, fasting insulin and fasting glucose in adults with overweight or obesity. METHODS: Randomized controlled trials were systematically searched before May 2014 in electronic databases and screening reference lists. Combined and stratified (diabetics and non-diabetics trials) meta-analyzes were performed. RESULTS: Thirteen trials, representing 513 adult participants with Body Mass Index ≥25 kg/m² were included. Prebiotic supplementation reduced plasma total cholesterol (SMD -0.25; 95% CI -0.48, -0.02) and LDL-c (SMD -0.22; 95% CI -0.44, -0.00) concentrations in overall analysis, and reduced triglycerides (SMD -0.72; 95% CI -1.20, -0.23) and increased HDL-c (SMD 0.49; 95% CI 0.01, 0.97) concentrations in diabetic trials. Synbiotic supplementation reduced plasma fasting insulin (SMD -0.39; 95% CI -0.75, -0.02) and triglycerides (SMD -0.43; 95% CI -0.70, -0.15) concentrations. CONCLUSIONS: The improvement of the evaluated parameters supports prebiotics and synbiotics supplementation as an adjuvant therapy in obesity-related comorbidities, such as dyslipidemia and insulin resistance.