Journal
DIABETES CARE
Volume 36, Issue 7, Pages 1933-1940Publisher
AMER DIABETES ASSOC
DOI: 10.2337/dc12-1925
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Funding
- European Union [223057]
- Kompetenznetz Adipositas (Competence Network for Adiposity)
- Federal Ministry of Education and Research, Germany [FKZ 01GI0845, FKZ 01EO1001]
- IFB Adiposity Diseases
- Eli Lilly and Co.
- Amylin Pharmaceuticals, Inc.
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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. RESEARCH DESIGN AND 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.
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