Dopamine production in neurotensin receptor 1 neurons is required for diet-induced obesity and increased day eating on a high-fat diet.
Journal
Obesity (Silver Spring, Md.)
ISSN: 1930-739X
Titre abrégé: Obesity (Silver Spring)
Pays: United States
ID NLM: 101264860
Informations de publication
Date de publication:
09 Jul 2024
09 Jul 2024
Historique:
revised:
17
04
2024
received:
14
02
2024
accepted:
30
04
2024
medline:
9
7
2024
pubmed:
9
7
2024
entrez:
9
7
2024
Statut:
aheadofprint
Résumé
This study aimed to determine a dopaminergic circuit required for diet-induced obesity in mice. We created conditional deletion mutants for tyrosine hydroxylase (TH) using neurotensin receptor 1 (Ntsr1) Cre and other Cre drivers and measured feeding and body weight on standard and high-fat diets. We then used an adeno-associated virus to selectively restore TH to the ventral tegmental area (VTA) Ntsr1 neurons in conditional knockout (cKO) mice. Mice with cKO of TH using Vglut2-Cre, Cck-Cre, Calb1-Cre, and Bdnf-Cre were susceptible to obesity on a high-fat diet; however, Ntsr1-Cre Th cKO mice resisted weight gain on a high-fat diet and did not experience an increase in day eating unlike their wild-type littermate controls. Restoration of TH to the VTA Ntsr1 neurons of the Ntsr1-Cre Th cKO mice using an adeno-associated virus resulted in an increase in weight gain and day eating on a high-fat diet. Ntsr1-Cre Th cKO mice failed to increase day eating on a high-fat diet, offering a possible explanation for their resistance to diet-induced obesity. These results implicate VTA Ntsr1 dopamine neurons as promoting out-of-phase feeding behavior on a high-fat diet that could be an important contributor to diet-induced obesity in humans.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : National Institute of General Medical Sciences and National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health
Informations de copyright
© 2024 The Obesity Society.
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