Effects of glucagon-like peptide 1 on appetite and body weight: focus on the CNS

Bloemendaal, Liselotte van; Kulve, Jennifer S. ten; Fleur, Susanne E. la; IJzerman, Richard G.; Diamant, Michaëla

doi:10.1530/joe-13-0414

Cited by 219 publications

(199 citation statements)

References 139 publications

(135 reference statements)

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“…Another GLP-1R agonist, liraglutide, has recently been approved as an anti-obesity drug because of abundant evidence of its prominent effect on weight loss (reviewed in van Bloemendaal et al [39]). A recent paper described how liraglutide did not affect BAT thermogenesis, but significantly reduced body weight and adiposity in obese mice [40].…”

Section: Discussionmentioning

confidence: 99%

GLP-1 receptor agonist promotes brown remodelling in mouse white adipose tissue through SIRT1

et al. 2016

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Aims/hypothesis Accumulating evidence has revealed the significant role of glucagon-like peptide-1 (GLP-1) in weight loss. Sirtuin 1 (SIRT1) plays a vital role in the regulation of lipid metabolism. Here, we investigated the contribution of lipolytic and oxidative changes in white adipose tissue (WAT) to the weight-lowering effect induced by the GLP-1 receptor (GLP-1R) agonist exenatide (exendin-4) in mice. We also looked at the role of SIRT1 in this process. Methods C57BL/6J mice and Sirt1 +/− mice were treated with exenatide (24 nmol/kg) or an NaCl solution (154 mmol/l) control i.p. for 8 weeks while receiving a high-fat diet (HFD) after a 12 week HFD challenge. Systemic phenotypic evaluations were carried out during and after the intervention. A lentivirus-mediated short hairpin (sh)RNA vector of the Sirt1 gene was transfected into differentiated 3T3-L1 adipocytes. An in vitro model system used adipocytes induced from Sirt1-null mouse embryonic fibroblasts (MEFs). Results Exenatide reduced fat mass and enhanced the lipolytic and oxidative capacity of WAT in diet-induced obese C57BL/ 6J mice. However, these effects were significantly impaired in Sirt1 +/− mice compared with wild-type controls. In vitro, exendin-4 increased lipolysis and fatty acid oxidation by upregulating SIRT1 expression and activity in differentiated 3T3-L1 adipocytes. Conversely, RNA interference (i)-induced knockdown of SIRT1 attenuated the lipolytic and oxidative responses to exendin-4 in differentiated 3T3-L1 adipocytes. Again, these responses were entirely abolished in Sirt1-null MEFs after induction into adipocytes. Conclusions/interpretation These data highlight that a GLP-1R agonist promotes brown remodelling of WAT in a SIRT1-dependent manner; this might be one of the mechanisms underlying its effect on weight loss.

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Section: Discussionmentioning

confidence: 99%

GLP-1 receptor agonist promotes brown remodelling in mouse white adipose tissue through SIRT1

et al. 2016

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“…Thus, GLP‐1 is also considered as a peripheral satiety hormone in mammals (Van Bloemendaal et al . 2014). In birds, intraperitoneal administration of 3 nmol/kg body weight GLP‐1 did not affect food intake in layer chicks under 15 h fasting (Tachibana et al .…”

Section: Introductionmentioning

confidence: 99%

“…2014). For example, GLP‐1 receptors in the subfornical organ and the area postrema are accessible to circulating GLP‐1 (Orskov et al .…”

Section: Introductionmentioning

confidence: 99%

Glucagon‐related peptides and the regulation of food intake in chickens

Honda

2016

Animal Science Journal

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The regulatory mechanisms underlying food intake in chickens have been a focus of research in recent decades to improve production efficiency when raising chickens. Lines of evidence have revealed that a number of brain‐gut peptides function as a neurotransmitter or peripheral satiety hormone in the regulation of food intake both in mammals and chickens. Glucagon, a 29 amino acid peptide hormone, has long been known to play important roles in maintaining glucose homeostasis in mammals and birds. However, the glucagon gene encodes various peptides that are produced by tissue‐specific proglucagon processing: glucagon is produced in the pancreas, whereas oxyntomodulin (OXM), glucagon‐like peptide (GLP)‐1 and GLP‐2 are produced in the intestine and brain. Better understanding of the roles of these peptides in the regulation of energy homeostasis has led to various physiological roles being proposed in mammals. For example, GLP‐1 functions as an anorexigenic neurotransmitter in the brain and as a postprandial satiety hormone in the peripheral circulation. There is evidence that OXM and GLP‐2 also induce anorexia in mammals. Therefore, it is possible that the brain‐gut peptides OXM, GLP‐1 and GLP‐2 play physiological roles in the regulation of food intake in chickens. More recently, a novel GLP and its specific receptor were identified in the chicken brain. This review summarizes current knowledge about the role of glucagon‐related peptides in the regulation of food intake in chickens.

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“…Increasing experimental and clinical evidence suggests that brain glucose metabolism is altered in patients with type 2 diabetes mellitus (T2DM) and contributes to the disturbance in whole-body glucose homeostasis (1,2). The brain receives multiple inputs including 1) hormones, such as leptin, ghrelin, peptide YY (PYY), glucagon like peptide-1 (GLP-1), and insulin, 2) nutrient-related signals that regulate fat accumulation in adipose tissue and hepatic and peripheral glucose metabolism, and 3) signals from the gastrointestinal tract through sensory nerves (1,2).…”

mentioning

confidence: 99%

“…The brain receives multiple inputs including 1) hormones, such as leptin, ghrelin, peptide YY (PYY), glucagon like peptide-1 (GLP-1), and insulin, 2) nutrient-related signals that regulate fat accumulation in adipose tissue and hepatic and peripheral glucose metabolism, and 3) signals from the gastrointestinal tract through sensory nerves (1,2).…”

mentioning

confidence: 99%

Exenatide Regulates Cerebral Glucose Metabolism in Brain Areas Associated With Glucose Homeostasis and Reward System

et al. 2015

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Glucagon-like peptide 1 receptors (GLP-1Rs) have been found in the brain, but whether GLP-1R agonists (GLP1RAs) influence brain glucose metabolism is currently unknown. The study aim was to evaluate the effects of a single injection of the GLP-1RA exenatide on cerebral and peripheral glucose metabolism in response to a glucose load. In 15 male subjects with HbA 1c of 5.7 6 0.1%, fasting glucose of 114 6 3 mg/dL, and 2-h glucose of 177 6 11 mg/dL, exenatide (5 mg) or placebo was injected in double-blind, randomized fashion subcutaneously 30 min before an oral glucose tolerance test (OGTT). The cerebral glucose metabolic rate (CMR glu ) was measured by positron emission tomography after an injection of [ 18 F]2-fluoro-2-deoxy-D-glucose before the OGTT, and the rate of glucose absorption (RaO) and disposal was assessed using stable isotope tracers. Exenatide reduced RaO 0-60 min (4.6 6 1.4 vs. 13.1 6 1.7 mmol/min $ kg) and decreased the rise in mean glucose 0-60 min (107 6 6 vs. 138 6 8 mg/dL) and insulin 0-60 min (17.3 6 3.1 vs. 24.7 6 3.8 mU/L). Exenatide increased CMR glu in areas of the brain related to glucose homeostasis, appetite, and food reward, despite lower plasma insulin concentrations, but reduced glucose uptake in the hypothalamus. Decreased RaO 0-60 min after exenatide was inversely correlated to CMR glu . In conclusion, these results demonstrate, for the first time in man, a major effect of a GLP-1RA on regulation of brain glucose metabolism in the absorptive state.

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Effects of glucagon-like peptide 1 on appetite and body weight: focus on the CNS

Cited by 219 publications

References 139 publications

GLP-1 receptor agonist promotes brown remodelling in mouse white adipose tissue through SIRT1

GLP-1 receptor agonist promotes brown remodelling in mouse white adipose tissue through SIRT1

Glucagon‐related peptides and the regulation of food intake in chickens

Exenatide Regulates Cerebral Glucose Metabolism in Brain Areas Associated With Glucose Homeostasis and Reward System

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