Detalle Publicación

ARTÍCULO
Hypothalamic dopamine signalling regulates brown fat thermogenesis
Autores: Folgueira, C.; Beiroa, D.; Porteiro, B. ; Duquenne, M. ; Puighermanal, E.; Fondevila, M. F. ; Barja-Fernandez, S.; Gallego, R. ; Hernandez-Bautista, R. ; Castelao, C. ; Senra, A. ; Seoane-Collazo, P. ; Gomez-Lado, N. ; Aguiar, P.; Guallar, D.; Fidalgo, M. ; Romero-Pico, A. ; Adan, R.; Blouet, C.; Labandeira-Garcia, J. L.; Jeanrenaud, F. ; Kallo, I.; Liposits, Z. ; Salvador Rodríguez, Javier; Prevot, V. ; Dieguez, C.; Lopez, M. ; Valjent, E.; Fruhbeck Martínez, Gema; Seoane, L. M. (Autor de correspondencia); Nogueiras, R. (Autor de correspondencia)
Título de la revista: NATURE METABOLISM
ISSN: 2522-5812
Volumen: 1
Número: 8
Páginas: 811 - 829
Fecha de publicación: 2019
Lugar: WOS
Resumen:
Dopamine signalling is a crucial part of the brain reward system and can affect feeding behaviour. 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 the 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 central nervous system to regulate energy balance.