小柯机器人

近日，法国波尔多大学Daniela Cota及其团队发现，下丘脑胆汁酸-TGR5信号途径可防止肥胖。这一研究成果于2021年4月21日在线发表在国际学术期刊《细胞—代谢》上。

研究人员表示，胆汁酸（BA）通过激活周围组织中的TGR5（Takeda G protein-coupled receptor 5）来改善新陈代谢并发挥抗肥胖作用。在脑下丘脑中也发现了TGR5，但是下丘脑BA信号是否与体重控制和肥胖症的病理生理有关尚不清楚。

研究人员发现，在饮食诱导的肥胖小鼠中，下丘脑BA含量降低。在这些动物中集中给予BA或特定的TGR5激动剂可通过激活交感神经系统来减轻体重和脂肪量，从而促进负能量平衡。相反，在中下丘脑中，TGR5基因表达的下调有利于肥胖症的发展，并通过减弱交感神经活动而恶化已建立的肥胖症。最后，下丘脑TGR5信号传导是膳食BA补充剂的抗肥胖作用所必需的。

总之，这些发现将下丘脑TGR5信号转导鉴定为自上而下神经机制的关键介质，从而抵抗饮食引起的肥胖。

附：英文原文

Title: Hypothalamic bile acid-TGR5 signaling protects from obesity

Author: Ashley Castellanos-Jankiewicz, Omar Guzmán-Quevedo, Valérie S. Fénelon, Philippe Zizzari, Carmelo Quarta, Luigi Bellocchio, Anne Tailleux, Julie Charton, Daniela Fernandois, Marcus Henricsson, Catherine Piveteau, Vincent Simon, Camille Allard, Sandrine Quemener, Valentine Guinot, Nathalie Hennuyer, Alessia Perino, Alexia Duveau, Marlène Maitre, Thierry Leste-Lasserre, Samantha Clark, Nathalie Dupuy, Astrid Cannich, Delphine Gonzales, Benoit Deprez, Gilles Mithieux, David Dombrowicz, Fredrik Bckhed, Vincent Prevot, Giovanni Marsicano, Bart Staels, Kristina Schoonjans, Daniela Cota

Issue&Volume: 2021-04-21

Abstract: Bile acids (BAs) improve metabolism and exert anti-obesity effects through the activationof the Takeda G protein-coupled receptor 5 (TGR5) in peripheral tissues. TGR5 is alsofound in the brain hypothalamus, but whether hypothalamic BA signaling is implicatedin body weight control and obesity pathophysiology remains unknown. Here we show thathypothalamic BA content is reduced in diet-induced obese mice. Central administrationof BAs or a specific TGR5 agonist in these animals decreases body weight and fat massby activating the sympathetic nervous system, thereby promoting negative energy balance.Conversely, genetic downregulation of hypothalamic TGR5 expression in the mediobasalhypothalamus favors the development of obesity and worsens established obesity byblunting sympathetic activity. Lastly, hypothalamic TGR5 signaling is required forthe anti-obesity action of dietary BA supplementation. Together, these findings identifyhypothalamic TGR5 signaling as a key mediator of a top-down neural mechanism thatcounteracts diet-induced obesity.

DOI: 10.1016/j.cmet.2021.04.009

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(21)00175-3

Cell Metabolism：《细胞—代谢》，创刊于2005年。隶属于细胞出版社，最新IF：31.373
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