GLP-1 receptor activation modulates appetite- and reward-related brain areas in humans.

Abstract

Gut-derived hormones, such as GLP-1, have been proposed to relay information to the brain to regulate appetite. GLP-1 receptor agonists, currently used for the treatment of type 2 diabetes (T2DM), improve glycemic control and stimulate satiety, leading to decreases in food intake and body weight. We hypothesized that food intake reduction after GLP-1 receptor activation is mediated through appetite- and reward-related brain areas. Obese T2DM patients and normoglycemic obese and lean individuals (n = 48) were studied in a randomized, crossover, placebo-controlled trial. Using functional MRI, we determined the acute effects of intravenous administration of the GLP-1 receptor agonist exenatide, with or without prior GLP-1 receptor blockade using exendin 9-39, on brain responses to food pictures during a somatostatin pancreatic-pituitary clamp. Obese T2DM patients and normoglycemic obese versus lean subjects showed increased brain responses to food pictures in appetite- and reward-related brain regions (insula and amygdala). Exenatide versus placebo decreased food intake and food-related brain responses in T2DM patients and obese subjects (in insula, amygdala, putamen, and orbitofrontal cortex). These effects were largely blocked by prior GLP-1 receptor blockade using exendin 9-39. Our findings provide novel insights into the mechanisms by which GLP-1 regulates food intake and how GLP-1 receptor agonists cause weight loss.

• Authors: Liselotte van Bloemendaal, Richard G IJzerman, Jennifer S Ten Kulve, Frederik Barkhof, Robert J Konrad, Madeleine L Drent, Dick J Veltman, Michaela Diamant
• Journal: Diabetes (Diabetes) Vol. 63 Issue 12 Pg. 4186-96 (Dec 2014) ISSN: 1939-327X [Electronic] United States
• PMID: 25071023 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Chemical References

• GLP1R protein, human
• Glucagon-Like Peptide-1 Receptor
• Hypoglycemic Agents
• Peptide Fragments
• Peptides
• Receptors, Glucagon
• Venoms
• exendin (9-39)
• Exenatide

Topics

• Adult
• Aged
• Amygdala (drug effects, metabolism, physiology)
• Appetite (drug effects, physiology)
• Brain (drug effects, metabolism, physiology)
• Case-Control Studies
• Cerebral Cortex (drug effects, metabolism, physiology)
• Cross-Over Studies
• Diabetes Mellitus, Type 2 (metabolism)
• Exenatide
• Feeding Behavior (drug effects, physiology)
• Female
• Functional Neuroimaging
• Glucagon-Like Peptide-1 Receptor
• Humans
• Hypoglycemic Agents (pharmacology)
• Magnetic Resonance Imaging
• Male
• Middle Aged
• Obesity (metabolism)
• Peptide Fragments (pharmacology)
• Peptides (pharmacology)
• Photic Stimulation
• Prefrontal Cortex (drug effects, metabolism, physiology)
• Putamen (drug effects, metabolism, physiology)
• Receptors, Glucagon (agonists, antagonists & inhibitors, physiology)
• Reward
• Venoms (pharmacology)