| Literature DB >> 31579887 |
Cintia Folgueira1,2,3, Daniel Beiroa2,3, Begoña Porteiro2,3, Manon Duquenne4, Emma Puighermanal5, Marcos F Fondevila2,3, Silvia Barja-Fernández1,3, Rosalia Gallego6, René Hernández-Bautista2, Cecilia Castelao1,3, Ana Senra2, Patricia Seoane2,3, Noemi Gómez7, Pablo Aguiar7, Diana Guallar2, Miguel Fidalgo2, Amparo Romero-Pico2,3, Roger Adan8, Clemence Blouet9, Jose Luís Labandeira-García2,10, Françoise Jeanrenaud11, Imre Kallo12, Zsolt Liposits12, Javier Salvador3,13, Vincent Prevot4, Carlos Dieguez2,3, Miguel Lopez2,3, Emmanuel Valjent5, Gema Frühbeck3,13, Luisa M Seoane1,3, Ruben Nogueiras2,3.
Abstract
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.Entities:
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Year: 2019 PMID： 31579887 PMCID： PMC6774781 DOI： 10.1038/s42255-019-0099-7
Source DB: PubMed Journal: Nat Metab ISSN： 2522-5812