Exenatide-Induced Reduction in Energy Intake Is AssociatedWith Increase in Hypothalamic Connectivity

OBJECTIVEdGlucagon-like peptide-1 receptor agonists like exenatide are known to influ-ence neural activity in the hypothalamus of animals and to reduce energy intake. In humans, however, significant weight loss has been observed in only a subgroup of patients. Why only some individuals respond with weight loss and others do not remains unclear. In this functional magnetic resonance imaging (fMRI) study, we investigated differences in hypothalamic connectivity between “responders ” (reduction in energy intake after exenatide infusion) and “nonresponders.” RESEARCHDESIGNANDMETHODSdWe performed a randomized, double-blinded, placebo-controlled, cross-over fMRI study with intravenous administration of exenatide in obese male volunteers. During brain scanning with continuous exenatide or placebo administration, participants rated food and nonfood images. After each scanning session, energy intake was measured using an ad libitum buffet. Functional hypothalamic connectivity was assessed by eigenvector centrality mapping, a measure of connectedness throughout the brain. RESULTSdResponders showed significantly higher connectedness of the hypothalamus, which was specific for the food pictures condition, in the exenatide condition compared wit