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Dorsolateral septum GLP-1R neurons regulate feeding via lateral hypothalamic projections
- Source :
- Molecular Metabolism, Vol 85, Iss , Pp 101960- (2024)
- Publication Year :
- 2024
- Publisher :
- Elsevier, 2024.
-
Abstract
- Objective: Although glucagon-like peptide 1 (GLP-1) is known to regulate feeding, the central mechanisms contributing to this function remain enigmatic. Here, we aim to test the role of neurons expressing GLP-1 receptors (GLP-1R) in the dorsolateral septum (dLS; dLSGLP−1R) that project to the lateral hypothalamic area (LHA) on food intake and determine the relationship with feeding regulation. Methods: Using chemogenetic manipulations, we assessed how activation or inhibition of dLSGLP−1R neurons affected food intake in Glp1r-ires-Cre mice. Then, we used channelrhodopsin-assisted circuit mapping, chemogenetics, and electrophysiological recordings to identify and assess the role of the pathway from dLSGLP−1R →LHA projections in regulating food intake. Results: Chemogenetic inhibition of dLSGLP−1R neurons increases food intake. LHA is a major downstream target of dLSGLP−1R neurons. The dLSGLP−1R→LHA projections are GABAergic, and chemogenetic inhibition of this pathway also promotes food intake. While chemogenetic activation of dLSGLP−1R→LHA projections modestly decreases food intake, optogenetic stimulation of the dLSGLP−1R→LHA projection terminals in the LHA rapidly suppresses feeding behavior. Finally, we demonstrate that the GLP-1R agonist, Exendin 4 enhances dLSGLP−1R →LHA GABA release. Conclusions: Together, these results demonstrate that dLS-GLP-1R neurons and the inhibitory pathway to LHA can regulate feeding behavior, which might serve as a potential therapeutic target for the treatment of eating disorders or obesity.
- Subjects :
- Septum
Hypothalamus
Feeding
Obesity
GLP-1
Internal medicine
RC31-1245
Subjects
Details
- Language :
- English
- ISSN :
- 22128778
- Volume :
- 85
- Issue :
- 101960-
- Database :
- Directory of Open Access Journals
- Journal :
- Molecular Metabolism
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.4deb670053f24139806e3d5ce6478696
- Document Type :
- article
- Full Text :
- https://doi.org/10.1016/j.molmet.2024.101960