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Randomized Controlled Trial
. 2014 Dec;63(12):4186-96.
doi: 10.2337/db14-0849. Epub 2014 Jul 28.

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

Liselotte van Bloemendaal  1 , Richard G IJzerman  2 , Jennifer S Ten Kulve  2 , Frederik Barkhof  3 , Robert J Konrad  4 , Madeleine L Drent  5 , Dick J Veltman  6 , Michaela Diamant  2
Affiliations
Randomized Controlled Trial

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

Liselotte van Bloemendaal et al. Diabetes. 2014 Dec.

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.

Trial registration: ClinicalTrials.gov NCT01281228.

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Comment in

  • Wired for obesity?
    Selvarajah D, Choudhary P, Farooqi IS. Selvarajah D, et al. Diabetes. 2014 Dec;63(12):4016-7. doi: 10.2337/db14-1311. Diabetes. 2014. PMID: 25414020 No abstract available.

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