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GLP-1 Receptor Activation Modulates Appetite, Rewards-Related Brain Areas

Study shows decrease in food intake and food-related brain responses…

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.

Researchers 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.

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Using functional MRI, they 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.

The findings provide novel insights into the mechanisms by which GLP-1 regulates food intake and how GLP-1 receptor agonists cause weight loss.

Practice Pearls:

  • In a randomized, crossover, placebo-controlled trial, researchers evaluated 48 patients to determine the acute effects of GLP-1 receptor antagonism using a functional MRI.
  • Patients with obesity or type 2 diabetes had increased brain responses to food pictures compared with patients who were lean.
  • Food intake and food-related brain responses were decreased in patients with obesity or type 2 diabetes receiving exenatide compared with patients receiving placebo.

L van Bloemendaal; Diabetes 2014 Dec 01;63(12)4186-4196, L van Bloemendaal, RG IJzerman, JS Ten Kulve, F Barkhof, RJ Konrad, ML Drent, DJ Veltman, M Diamant.