Hypothalamic dopamine signaling regulates brown fat thermogenesis.
Journal
Nature metabolism
ISSN: 2522-5812
Titre abrégé: Nat Metab
Pays: Germany
ID NLM: 101736592
Informations de publication
Date de publication:
08 2019
08 2019
Historique:
entrez:
4
10
2019
pubmed:
4
10
2019
medline:
4
10
2019
Statut:
ppublish
Résumé
Dopamine signaling is a crucial part of the brain reward system and can affect feeding behavior. Dopamine receptors are also expressed in the hypothalamus, which is known to control energy metabolism in peripheral tissues. Here we show that pharmacological or chemogenetic stimulation of dopamine receptor 2 (D2R) expressing cells in the lateral hypothalamic area (LHA) and the zona incerta (ZI) decreases body weight and stimulates brown fat activity in rodents in a feeding-independent manner. LHA/ZI D2R stimulation requires an intact sympathetic nervous system and orexin system to exert its action and involves inhibition of PI3K in the LHA/ZI. We further demonstrate that, as early as 3 months after onset of treatment, patients treated with the D2R agonist cabergoline experience an increase in energy expenditure that persists for one year, leading to total body weight and fat loss through a prolactin-independent mechanism. Our results may provide a mechanistic explanation for how clinically used D2R agonists act in the CNS to regulate energy balance.
Identifiants
pubmed: 31579887
doi: 10.1038/s42255-019-0099-7
pmc: PMC6774781
mid: EMS84394
doi:
Substances chimiques
Bromocriptine
3A64E3G5ZO
Dopamine
VTD58H1Z2X
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Pagination
811-829Subventions
Organisme : European Research Council
ID : 810331
Pays : International
Déclaration de conflit d'intérêts
The authors declare no conflict of interests.
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