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GLP-1 receptor agonists change how brain responds to food
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BOSTON — Gut hormone-based therapies used to treat type 2 diabetes alter the brain’s response to food, which may reduce food cravings and increase satisfaction while eating, according to study findings presented here.
In a randomized, placebo-controlled, crossover study that used functional MRI to measure the brain responses of adults with and without type 2 diabetes and obesity, researchers also found that IV infusion of the glucagon-like peptide-1 receptor agonist Byetta (exenatide, AstraZeneca) alters central nervous system reactions to both the anticipation and consumption of palatable food.
“We have previously shown that an acute infusion of GLP-1 receptor agonists reduces brain responses to watching food pictures,” Liselotte van Bloemendaal, MD, a PhD student at the Diabetes Center at VU University Medical Center in Amsterdam, said in a press conference announcing the study findings. “But the effects of GLP-1 receptor agonists on actual food consumption may be even more important.”
Liselotte van Bloemendaal
Van Bloemendaal and colleagues analyzed data from 48 participants divided into three groups. Within the cohort, 16 adults (mean age, 61 years; eight men; mean BMI, 34 kg/m2) had obesity and type 2 diabetes; 15 adults (mean age, 58 years; eight men; mean BMI, 33 kg/m2) had obesity; and 16 adults (mean age, 58 years; eight men; mean BMI, 23 kg/m2) had a lean body weight.
Researchers used functional MRI to determine the effects of GLP-1 receptor activation on brain responses to both the anticipation and receipt of chocolate milk vs. a tasteless solution. Each participant underwent three functional MRI sessions at separate visits, receiving an IV infusion of either exenatide, exenatide with exendin 9-39 (a GLP-1 receptor blockade) or matched placebo during somatostatin pituitary-pancreatic clamps.
After treatment, researchers found participants assigned exenatide showed an increased brain response to the receipt of chocolate milk in the areas of the brain regulating reward, appetite and motivation and decreased anticipation of receiving the chocolate milk vs. those assigned placebo. Exendin 9-39 largely prevented these effects, according to researchers.
In addition, researchers found BMI also was positively correlated with the anticipation of chocolate milk, and negatively correlated with the brain response to receipt of chocolate milk.
“We found that individuals with a higher BMI had increased brain responses when they were anticipating chocolate milk receipt, and in addition, a higher BMI was correlated with a decreased brain reward system activation in response to actual receipt of the chocolate milk,” van Bloemendaal said. “Interestingly, the GLP-1 receptor agonist exenatide increased brain responses to receipt of the chocolate milk and decreased anticipation of response to the chocolate milk.”
“Our findings provide novel insights into the mechanisms by which GLP-1 regulates food intake and how GLP-1 receptor agonists induce weight loss,” the researchers wrote.
Long-term studies are of interest, Bloemendaal said, to determine whether these effects also are present during longer term use of GLP-1 receptor agonists.
“These insights may help to develop new treatments for obesity,” Bloemendaal said. – by Regina Schaffer
Reference:
van Bloemendaal L, et al. Abstract 384-OR. Presented at: American Diabetes Association’s 75th Scientific Sessions; June 5-9, 2015; Boston.
Disclosure: van Bloemendaal reports no relevant financial disclosures. Please see the full study for a list of all other authors’ relevant financial disclosures.