Exenatide-induced reduction in energy intake is associated with increase in hypothalamic connectivity
- PMID: 23462665
- PMCID: PMC3687323
- DOI: 10.2337/dc12-1925
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."
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.
Figures
![Figure 1](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/3687323/bin/1933fig1.gif)
![Figure 2](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/3687323/bin/1933fig2.gif)
![Figure 3](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/3687323/bin/1933fig3.gif)
![Figure 4](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/3687323/bin/1933fig4.gif)
Similar articles
-
Exenatide has a pronounced effect on energy intake but not energy expenditure in non-diabetic subjects with obesity: A randomized, double-blind, placebo-controlled trial.Metabolism. 2018 Aug;85:116-125. doi: 10.1016/j.metabol.2018.03.017. Epub 2018 Mar 26. Metabolism. 2018. PMID: 29596853 Free PMC article. Clinical Trial.
-
Effects of exenatide versus sitagliptin on postprandial glucose, insulin and glucagon secretion, gastric emptying, and caloric intake: a randomized, cross-over study.Curr Med Res Opin. 2008 Oct;24(10):2943-52. doi: 10.1185/03007990802418851. Epub 2008 Sep 10. Curr Med Res Opin. 2008. PMID: 18786299 Clinical Trial.
-
Discordance Between Central (Brain) and Pancreatic Action of Exenatide in Lean and Obese Subjects.Diabetes Care. 2016 Oct;39(10):1804-10. doi: 10.2337/dc15-2706. Epub 2016 Aug 3. Diabetes Care. 2016. PMID: 27489336 Free PMC article.
-
Exenatide and weight loss.Nutrition. 2010 Mar;26(3):243-9. doi: 10.1016/j.nut.2009.07.008. Nutrition. 2010. PMID: 20152707 Review.
-
Exenatide: a GLP-1 receptor agonist as novel therapy for Type 2 diabetes mellitus.Expert Opin Pharmacother. 2006 Jun;7(8):1055-64. doi: 10.1517/14656566.7.8.1055. Expert Opin Pharmacother. 2006. PMID: 16722815 Review.
Cited by
-
Update on Pediatric Anti-obesity Medications-Current Landscape and Approach to Prescribing.Curr Obes Rep. 2024 Jun;13(2):295-312. doi: 10.1007/s13679-024-00566-z. Epub 2024 Apr 30. Curr Obes Rep. 2024. PMID: 38689134 Review.
-
Evaluating the effectiveness and underlying mechanisms of incretin-based treatments for hypothalamic obesity: A narrative review.Obes Pillars. 2024 Feb 24;10:100104. doi: 10.1016/j.obpill.2024.100104. eCollection 2024 Jun. Obes Pillars. 2024. PMID: 38463533 Free PMC article. Review.
-
Gut hormone co-agonists for the treatment of obesity: from bench to bedside.Nat Metab. 2023 Jun;5(6):933-944. doi: 10.1038/s42255-023-00812-z. Epub 2023 Jun 12. Nat Metab. 2023. PMID: 37308724 Review.
-
The treatment of obesity in children and adolescents: consensus position statement of the Italian society of pediatric endocrinology and diabetology, Italian Society of Pediatrics and Italian Society of Pediatric Surgery.Ital J Pediatr. 2023 Jun 8;49(1):69. doi: 10.1186/s13052-023-01458-z. Ital J Pediatr. 2023. PMID: 37291604 Free PMC article. Review.
-
Reward Processing During Monetary Incentive Delay Task After Leptin Substitution in Lipodystrophy-an fMRI Case Series.J Endocr Soc. 2023 Apr 20;7(6):bvad052. doi: 10.1210/jendso/bvad052. eCollection 2023 May 5. J Endocr Soc. 2023. PMID: 37180211 Free PMC article.
References
-
- Holst JJ. The physiology of glucagon-like peptide 1. Physiol Rev 2007;87:1409–1439 - PubMed
-
- Sze L, Purtell L, Jenkins A, et al. . Effects of a single dose of exenatide on appetite, gut hormones, and glucose homeostasis in adults with Prader-Willi syndrome. J Clin Endocrinol Metab 2011;96:E1314–E1319 - PubMed
-
- Campos RV, Lee YC, Drucker DJ. Divergent tissue-specific and developmental expression of receptors for glucagon and glucagon-like peptide-1 in the mouse. Endocrinology 1994;134:2156–2164 - PubMed
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources