title: 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: Diabetes Center, Department of Internal Medicine, VU University Medical Center, Amsterdam, the Netherlands l.vanbloemendaal@vumc.nl.
authors: Liselotte
authors: L
authors: van Bloemendaal
authors: Diabetes Center, Department of Internal Medicine, VU University Medical Center, Amsterdam, the Netherlands.
authors: Richard G
authors: RG
authors: IJzerman
authors: Diabetes Center, Department of Internal Medicine, VU University Medical Center, Amsterdam, the Netherlands.
authors: Jennifer S
authors: JS
authors: Ten Kulve
authors: Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, the Netherlands.
authors: Frederik
authors: F
authors: Barkhof
authors: Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN.
authors: Robert J
authors: RJ
authors: Konrad
authors: Endocrine Section, Department of Internal Medicine, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, the Netherlands.
authors: Madeleine L
authors: ML
authors: Drent
authors: Department of Psychiatry, VU University Medical Center, Amsterdam, the Netherlands.
authors: Dick J
authors: DJ
authors: Veltman
authors: Diabetes Center, Department of Internal Medicine, VU University Medical Center, Amsterdam, the Netherlands.
authors: Michaela
authors: M
authors: Diamant
mesh_terms: D000328:Adult; D000368:Aged; D000679:Amygdala / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D001066:Appetite / Q000187:drug effects / Q000502:physiology*; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D016022:Case-Control Studies; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D000077270:Exenatide; D005247:Feeding Behavior / Q000187:drug effects / Q000502:physiology*; D005260:Female; D059907:Functional Neuroimaging; D000067757:Glucagon-Like Peptide-1 Receptor; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D010775:Photic Stimulation; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D011699:Putamen / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D018027:Receptors, Glucagon / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D012201:Reward; D014688:Venoms / Q000494:pharmacology
chemical_list: C000593833:GLP1R protein, human; D000067757:Glucagon-Like Peptide-1 Receptor; D007004:Hypoglycemic Agents; D010446:Peptide Fragments; D010455:Peptides; D018027:Receptors, Glucagon; D014688:Venoms; C083773:exendin (9-39); D000077270:Exenatide