title: Exenatide-induced reduction in energy intake is associated with increase in hypothalamic connectivity.
abstract: OBJECTIVE
  Glucagon-like peptide-1 receptor agonists such as exenatide are known to influence 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."
  
  
  METHODS
  We 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.
  
  
  RESULTS
  Responders showed significantly higher connectedness of the hypothalamus, which was specific for the food pictures condition, in the exenatide condition compared with placebo. Nonresponders did not show any significant exenatide-induced changes in hypothalamic connectedness.
  
  
  CONCLUSIONS
  Our results demonstrate a central hypothalamic effect of peripherally administered exenatide that occurred only in the group that showed an exenatide-dependent anorexigenic effect. These findings indicate that the hypothalamic response seems to be the crucial factor for the effect of exenatide on energy intake.
authors: Department of Medicine, University of Leipzig, Leipzig, Germany.
authors: Haiko
authors: H
authors: Schlögl
authors: Stefan
authors: S
authors: Kabisch
authors: Annette
authors: A
authors: Horstmann
authors: Gabriele
authors: G
authors: Lohmann
authors: Karsten
authors: K
authors: Müller
authors: Jöran
authors: J
authors: Lepsien
authors: Franziska
authors: F
authors: Busse-Voigt
authors: Jürgen
authors: J
authors: Kratzsch
authors: Burkhard
authors: B
authors: Pleger
authors: Arno
authors: A
authors: Villringer
authors: Michael
authors: M
authors: Stumvoll
mesh_terms: D000328:Adult; D000465:Algorithms; D001786:Blood Glucose / Q000378:metabolism; D018592:Cross-Over Studies; D004311:Double-Blind Method; D002149:Energy Intake / Q000187:drug effects*; D000077270:Exenatide; D006801:Humans; D007031:Hypothalamus / Q000187:drug effects*; D007328:Insulin / Q000097:blood; D008279:Magnetic Resonance Imaging; D008297:Male; D010455:Peptides / Q000494:pharmacology*; D014688:Venoms / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D007328:Insulin; D010455:Peptides; D014688:Venoms; D000077270:Exenatide