Hypothalamic bile acid-TGR5 signaling protects from obesity - Archive ouverte HAL Access content directly
Journal Articles Cell Metabolism Year : 2021

Hypothalamic bile acid-TGR5 signaling protects from obesity

(1) , (2, 1) , (1) , (1) , (1) , (1) , (3) , (4) , (5) , (6) , (4) , (1) , (1) , (3) , (3) , (3) , (7) , (1) , (1) , (1) , (1) , (1) , (1) , (1) , (4, 1) , (8, 9) , (3) , (10) , (5) , (1) , (3) , (7) , (1)
1
2
3
4
5
6
7
8
9
10
Marcus Henricsson
Vincent Prevot

Abstract

Bile acids (BAs) improve metabolism and exert anti-obesity effects through the activation of the Takeda G protein-coupled receptor 5 (TGR5) in peripheral tissues. TGR5 is also found in the brain hypothalamus, but whether hypothalamic BA signaling is implicated in body weight control and obesity pathophysiology remains unknown. Here we show that hypothalamic BA content is reduced in diet-induced obese mice. Central administration of BAs or a specific TGR5 agonist in these animals decreases body weight and fat mass by activating the sympathetic nervous system, thereby promoting negative energy balance. Conversely, genetic downregulation of hypothalamic TGR5 expression in the mediobasal hypothalamus favors the development of obesity and worsens established obesity by blunting sympathetic activity. Lastly, hypothalamic TGR5 signaling is required for the anti-obesity action of dietary BA supplementation. Together, these findings identify hypothalamic TGR5 signaling as a key mediator of a top-down neural mechanism that counteracts diet-induced obesity.
Fichier principal
Vignette du fichier
draft_Castellanos et al_Cell Metab 2021_.pdf (3.43 Mo) Télécharger le fichier
Origin : Files produced by the author(s)

Dates and versions

inserm-03257931 , version 1 (11-06-2021)

Identifiers

Cite

Ashley Castellanos-Jankiewicz, Omar Guzmán-Quevedo, Valérie Fénelon, Philippe Zizzari, Carmelo Quarta, et al.. Hypothalamic bile acid-TGR5 signaling protects from obesity. Cell Metabolism, 2021, 33 (7), pp.1483-1492.e10. ⟨10.1016/j.cmet.2021.04.009⟩. ⟨inserm-03257931⟩
79 View
71 Download

Altmetric

Share

Gmail Facebook Twitter LinkedIn More