24. Brain Reward-System Activation in Response to Anticipation and Consumption of Palatable Food Is Altered by GLP-1 Receptor Activation in Humans (384-OR)

Abstract

It has been suggested that obese individuals have increased brain reward system activation while anticipating food intake, which may lead to cravings for food, and decreased reward system activation during actual food consumption, which may induce overeating. Gut-derived hormones, such as glucagon-like peptide-1 (GLP-1), are likely involved in the regulation of food intake. GLP-1 receptor agonists improve glycemic control and reduce food intake and body weight. We hypothesized that food intake reduction following GLP-1 receptor activation is mediated through brain areas regulating anticipatory and consummatory food reward. Using functional MRI, we determined the effects of GLP-1 receptor activation on brain responses to anticipation and receipt of chocolate milk vs. tasteless solution. Obese T2DM patients, normoglycemic obese and lean subjects (n = 48) underwent three functional MRI sessions at separate visits with intravenous infusion of A) the GLP-1 receptor agonist exenatide, B) exenatide with prior GLP-1 receptor blockade by exendin 9-39 or C) placebo; during somatostatin pituitary-pancreatic clamps. We found that BMI negatively correlated with brain responses to receipt of chocolate milk and positively correlated with anticipation of receipt of chocolate milk in brain areas regulating reward, appetite and motivation. Exenatide vs. placebo increased brain responses to receipt of chocolate milk and decreased anticipation of receipt of chocolate milk, paralleled by reductions in food intake. Exendin 9-39 largely prevented these effects. GLP-1 receptor activation decreased anticipatory food reward, which may reduce cravings for food, and increased consummatory food reward, which may prevent overeating. Our findings provide novel insights into the mechanisms by which GLP-1 regulates food intake and how GLP-1 receptor agonists induce weight loss.