OR15-2 GLP-1 Receptors Exist in the Parietal Cortex, Hypothalamus, and Medulla of Human Brains and the GLP-1 Analog Liraglutide Administered in the Context of a Cross-over, Randomized, Placebo-Controlled Trial Alters Brain Activity in Response to Highly Desirable Food Cues in Individuals with Diabetes

Program: Abstracts - Orals, Poster Previews, and Posters
Session: OR15-Novel Treatment for Diabetes - Focusing on GLP-1 and SGLT2
Saturday, April 2, 2016: 11:45 AM-1:15 PM
Presentation Start Time: 12:00 PM
Room 157 (BCEC)

Outstanding Abstract Award
Olivia M. Farr*1, Michail Sofopoulos2, Michael A. Tsoukas1, Fadime Dincer3, Bindiya Thakkar4, Ayse Sahin-Efe5, Andreas Filippaios3, Jennifer Bowers3, Alexandra Srnka3, Anna Gavrieli3, Byung-Joon Ko3, Chrysoula Liakou2, Nickole Kanyuch3, Sofia Tseleni-Balafouta6 and Christos S. Mantzoros7
1Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 2St. Savvas Anticancer-Oncology Hospital, 3Harvard Medical School/ Beth Israel Deaconess Medical Center, 4Harvard Medical School/ Beth Israel Deaconess Medical Center, Boston, MA, 5Harvard Medical School/ Beth Israel Deaconess, 6University of Athens, Medical School, 7BIDMC, Harvard, Boston, MA
Obesity and type 2 diabetes (DM) are becoming epidemics for which effective treatments are increasingly required. Liraglutide is a glucagon-like peptide-1 (GLP-1) analog which has been demonstrated to successfully treat diabetes and promote weight loss. The mechanisms, including any central mechanisms, by which liraglutide may confer weight loss remains to be fully clarified. Thus, we studied whether GLP-1 receptors are expressed in human brains and examined whether liraglutide administration may impact neural responses to food cues in diabetics.  Study 1: In 22 consecutively studied human brains, expression of GLP-1 receptors was examined using immunohistochemistry (IHC) in the hypothalamus, medulla oblongata, and parietal cortex. Study 2: In 18 subjects with DM who were treated with placebo and liraglutide in the context of a randomized, placebo-controlled, double-blind, cross-over trial for a total of 17 days each (0.6 mg for 7 days, 1.2 mg for 7 days and 1.8 mg for 3 days), we studied metabolic changes as well as neurocognitive and neuroimaging (fMRI) responses to food cues. IHC revealed GLP-1 receptors on neurons in the human hypothalamus, medulla, and parietal cortex. Liraglutide decreased activation of the parietal cortex in response to highly desirable as compared to less desirable food images. In a secondary analysis, we also observe decreased activation in the insula and putamen, areas involved in the reward system. Furthermore, we show that increased ratings of hunger and appetite correlate with increased brain activations in parietal and visual cortices to highly desirable food cues while on liraglutide. On the other hand, ratings of nausea correlate to decreased brain activation in cingulate cortex. There are no activations in the hypothalamus. For the first time, we demonstrate GLP-1 receptors in human brains. We also observe that liraglutide alters attention-related brain activity in the parietal cortex to highly desirable food cues. Our data point to a central mechanism contributing to or underlying effects of liraglutide on metabolism/weight loss. Future studies will be needed to confirm and extend these findings in larger samples of diabetics and/or with higher doses of liraglutide (3 mg) recently approved for obesity.

Disclosure: CSM: Scientific Board Member, Novo Nordisk. Nothing to Disclose: OMF, MS, MAT, FD, BT, AS, AF, JB, AS, AG, BJK, CL, NK, ST

*Please take note of The Endocrine Society's News Embargo Policy at https://www.endocrine.org/news-room/endo-annual-meeting/pr-resources-for-endo

Sources of Research Support: NIH 5T32HD052961; NIH UL1 RR025758; Novo Nordisk Investigator-Initiated Study