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Integration of Glucagon-Like Peptide 1 Receptor Actions Through the Central Amygdala

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Journal Endocrinology
Date 2025 Jan 31
PMID 39888375
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Abstract

Understanding the detailed mechanism of action of glucagon-like peptide 1 receptor (GLP-1R) agonists on distinct topographic and genetically defined brain circuits is critical for improving the efficacy and mitigating adverse side effects of these compounds. In this mini-review, we propose that the central nucleus of the amygdala (CeA) is a critical mediator of GLP-1R agonist-driven hypophagia. Here, we review the extant literature demonstrating CeA activation via GLP-1R agonists across multiple species and through multiple routes of administration. The precise role of GLP-1Rs within the CeA is unclear but the site-specific GLP-1Rs may mediate distinct behavioral and physiological hallmarks of GLP-1R agonists on food intake. Thus, we propose important novel directions and methods to test the role of the CeA in mediating GLP-1R actions.

References
1.
Edwards C, Todd J, Mahmoudi M, Wang Z, Wang R, Ghatei M . Glucagon-like peptide 1 has a physiological role in the control of postprandial glucose in humans: studies with the antagonist exendin 9-39. Diabetes. 1999; 48(1):86-93. DOI: 10.2337/diabetes.48.1.86. View

2.
Steinberg E, Gore F, Heifets B, Taylor M, Norville Z, Beier K . Amygdala-Midbrain Connections Modulate Appetitive and Aversive Learning. Neuron. 2020; 106(6):1026-1043.e9. DOI: 10.1016/j.neuron.2020.03.016. View

3.
Yang D, Wang Y, Qi T, Zhang X, Shen L, Ma J . Phosphorylation of pyruvate dehydrogenase inversely associates with neuronal activity. Neuron. 2024; 112(6):959-971.e8. PMC: 11021214. DOI: 10.1016/j.neuron.2023.12.015. View

4.
Arillotta D, Floresta G, Guirguis A, Corkery J, Catalani V, Martinotti G . GLP-1 Receptor Agonists and Related Mental Health Issues; Insights from a Range of Social Media Platforms Using a Mixed-Methods Approach. Brain Sci. 2023; 13(11). PMC: 10669484. DOI: 10.3390/brainsci13111503. View

5.
Huang K, Acosta A, Ghidewon M, McKnight A, Almeida M, Nyema N . Dissociable hindbrain GLP1R circuits for satiety and aversion. Nature. 2024; 632(8025):585-593. DOI: 10.1038/s41586-024-07685-6. View