Dorsolateral septum GLP-1R neurons regulate feeding via lateral hypothalamic projections.
Mol Metab
; 85: 101960, 2024 Jul.
Article
em En
| MEDLINE
| ID: mdl-38763494
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 âLHA 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-1RâLHA projections are GABAergic, and chemogenetic inhibition of this pathway also promotes food intake. While chemogenetic activation of dLSGLP-1RâLHA projections modestly decreases food intake, optogenetic stimulation of the dLSGLP-1RâLHA projection terminals in the LHA rapidly suppresses feeding behavior. Finally, we demonstrate that the GLP-1R agonist, Exendin 4 enhances dLSGLP-1R âLHA 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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Receptor do Peptídeo Semelhante ao Glucagon 1
/
Região Hipotalâmica Lateral
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Neurônios
Limite:
Animals
Idioma:
En
Revista:
Mol Metab
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Estados Unidos