Hypothalamic dopamine signalling regulates brown fat thermogenesis

Cintia Folgueira, Daniel Beiroa, Begoña Porteiro, Manon Duquenne, Emma Puighermanal, Marcos F. Fondevila, Silvia Barja-Fernández, Rosalia Gallego, René Hernández-Bautista, Cecilia Castelao, Ana Senra, Patricia Seoane-Collazo, Noemi Gómez-Lado, Pablo Aguiar, Diana Guallar, Miguel Fidalgo, Amparo Romero-Pico, Roger Adan, Clemence Blouet, Jose Luís Labandeira-GarcíaFrançoise Jeanrenaud, Imre Kallo, Zsolt Liposits, Javier Salvador, Vincent Prevot, Carlos Dieguez, Miguel López, Emmanuel Valjent, Gema Frühbeck, Luisa M. Seoane, Ruben Nogueiras

Research output: Contribution to journalArticlepeer-review

39 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)811-829
Number of pages19
JournalNature Metabolism
Volume1
Issue number8
DOIs
StatePublished - 1 Aug 2019
Externally publishedYes

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