GLP-1 Agonists May Change How Brain Responds to Food

Glucagon-like peptide (GLP)-1 receptor agonists may help patients with type 2 diabetes lose weight by altering the way their brains respond to food, according to the results of a study presented recently at the American Diabetes Association's 75th Scientific Sessions.

According to the study, obese individuals may have an increased brain reward system that is activated during the anticipation of food intake, increasing cravings, but decreased during actual food consumption, increasing overeating.

“When you eat, there are several hormones released. GLP-1 is one of them,” Liselotte van Bloemendaal, MD, a PhD student at the Diabetes Center, VU University Medical Center in Amsterdam, said. “We found that GLP-1 receptor activation decreased anticipatory food reward, which may reduce cravings, and increased the feeling of food reward during consumption, which may reduce overeating."

The study included 48 subjects who were either obese patients with type 2 diabetes, or normoglycemic obese and lean patients. Patients underwent three functional MRI sessions with intravenous infusions of either exenatide, exenatide with prior GLP-1 receptor blockage by exendin 9-39, or placebo. The researchers used MRI to observe the reward centers in the patients’ brains and to measure their responses of anticipation and receipt of either chocolate milk or a tasteless solution.

Van Bloemendaal and colleagues found that BMI was negatively associated with the brain’s response to receipt of chocolate milk, but was positively associated with anticipation of receipt of chocolate milk in the areas of the brain that regulate reward, appetite, and motivation.

Receipt of the GLP-1 receptor agonist exenatide was found to increase brain response to receipt of chocolate milk, and decrease the anticipation of the receipt of the chocolate milk. This paralleled reductions in food intake.

"Given the dramatic, global rise in the prevalence of obesity, further insights into the mechanisms by which these reward centers are activated are needed," van Bloemendaal said, adding that one avenue that merits further investigation would be to study whether adding a second hormone, such as glucagon, to GLP-1 receptor agonist treatment could further increase weight loss.

References:

Van Bloemendaal L, et al. Abstract #384-OR. Brain reward-system activation in response to anticipation and consumption of palatable food if altered by GLP-1 receptor activation in humans. Presented at: American Diabetes Association's 75th Scientific Sessions. http://diabetes.diabetesjournals.org/content/63/12/4186.short?rss=1

American Diabetes Association. GLP-1 alters how the brain responds to food. 9 June 2015. http://www.diabetes.org/newsroom/press-releases/2015/glp-1-alters-how-the-brain-responds-to-food.html