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  Exenatide-induced reduction in energy intake is associated with increase in hypothalamic connectivity

Schlögl, H., Kabisch, S., Horstmann, A., Lohmann, G., Mueller, K., Lepsien, J., et al. (2013). Exenatide-induced reduction in energy intake is associated with increase in hypothalamic connectivity. Diabetes Care, 36(7), 1933-1940. doi:10.2337/dc12-1925.

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Schlögl, Haiko1, Author           
Kabisch, Stefan1, Author           
Horstmann, Annette2, 3, Author           
Lohmann, Gabriele4, Author           
Mueller, Karsten5, Author           
Lepsien, Jöran5, Author           
Busse, Franziska P.1, Author           
Kratzsch, Jürgen6, Author
Pleger, Burkhard2, 7, Author           
Villringer, Arno2, 7, Author           
Stumvoll, Michael1, 3, Author
Affiliations:
1Faculty of Medicine, University of Leipzig, Germany, ou_persistent22              
2Department Neurology, MPI for Human Cognitive and Brain Sciences, Max Planck Society, ou_634549              
3Integrated Research and Treatment Center Adiposity Diseases, University of Leipzig, Germany, ou_persistent22              
4Department Neurophysics, MPI for Human Cognitive and Brain Sciences, Max Planck Society, ou_634550              
5Methods and Development Unit Nuclear Magnetic Resonance, MPI for Human Cognitive and Brain Sciences, Max Planck Society, ou_634558              
6Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics (ILM), University of Leipzig, Germany, ou_persistent22              
7Clinic for Cognitive Neurology, University of Leipzig, Germany, ou_persistent22              

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 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." 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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Language(s): eng - English
 Dates: 2013-03-052013-07
 Publication Status: Issued
 Pages: -
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 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.2337/dc12-1925
PMID: 23462665
PMC: PMC3687323
Other: Epub 2013
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Title: Diabetes Care
Source Genre: Journal
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Publ. Info: Alexandria, VA : American Diabetes Association
Pages: - Volume / Issue: 36 (7) Sequence Number: - Start / End Page: 1933 - 1940 Identifier: ISSN: 0149-5992
CoNE: https://pure.mpg.de/cone/journals/resource/110978984565249