The Endocrine Society's 98th Annual Meeting & Expo:
GLP-1 Receptors in Human Brain; Liraglutide Decreased Reward Responses to Highly Desirable Food Cues
Liraglutide, a glucagon-like peptide-1 analogue (GLP-1), used to treat diabetes, and recently approved for obesity, has been found to promote weight loss. "As we all know, diabetes and obesity are increasing problems in the United States and other industrialized countries, and we increasingly need new treatments for both diseases," said study co-author Olivia M. Farr, PhD. Dr. Farr is an Instructor in Medicine at Beth-Israel Deaconess Medical Center at Harvard Medical School in Boston.
"Our main findings are that GLP-1 —glucagon-like peptide 1 receptors— exist in the human brain, which is a novel finding, particularly in the cortex. We found that it decreased the attractiveness of highly desirable high-calorie or high-fat food cues. We also found that it decreased reward-related activations to these same highly desirable food cues," stated Dr. Farr.
In a preliminary study, immunohistochemistry was used to analyze 22 human brains for expression of GLP-1 in the hypothalamus, medulla oblongata and parietal cortex. In the second study, 18 subjects with type 2 diabetes were randomized to receive placebo and liraglutide. After a 3-week wash out period, the same study participants received the opposite treatment.
Dr. Farr explained, "They received placebo throughout a solid phase, but for liraglutide we titrated the dose from 0.6 mg for a week to 1.2 mg for a week and then 1.8 mg for three days, so in total it was 17 days for each phase. At the end of those 17 days, they had an overnight visit to ensure that they were fasting, and then we did a functional magnetic resonance imaging protocol while they viewed food cues."
On the 17th day of each study phase, the subjects underwent functional magnetic resonance imaging of their brains while viewing food and non-food cues. Visual cues included high and low calorie/fat foods and non-food images, such as flowers.
"We found liraglutide decreased activation in the parietal cortex to these highly desirable food cues; so it's selectively decreasing attention or attractiveness to these high calorie or high fat food cues," said Dr. Farr. Furthermore, she stated, "Liraglutide decreased reward-related activations in the insula and putamen to these same highly desirable food cues."
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