Hypothalamic bile acid-TGR5 signaling protects from obesity

被引：174

作者：

Castellanos-Jankiewicz, Ashley ^{[1
]}

Guzman-Quevedo, Omar ^{[1
,2
,3
]}

Fenelon, Valerie S. ^{[1
]}

Zizzari, Philippe ^{[1
]}

Quarta, Carmelo ^{[1
]}

Bellocchio, Luigi ^{[1
]}

Tailleux, Anne ^{[4
]}

Charton, Julie ^{[5
]}

Fernandois, Daniela ^{[6
]}

Henricsson, Marcus ^{[7
]}

Piveteau, Catherine ^{[8
]}

Simon, Vincent ^{[1
]}

Allard, Camille ^{[1
]}

Quemener, Sandrine ^{[4
]}

Guinot, Valentine ^{[4
]}

Hennuyer, Nathalie ^{[4
]}

Perino, Alessia ^{[9
]}

Duveau, Alexia ^{[1
]}

Maitre, Marlene ^{[1
]}

Leste-Lasserre, Thierry ^{[1
]}

Clark, Samantha ^{[1
]}

Dupuy, Nathalie ^{[1
]}

Cannich, Astrid ^{[1
]}

Gonzales, Delphine ^{[1
]}

Deprez, Benoit ^{[5
]}

Mithieux, Gilles ^{[10
]}

Dombrowicz, David ^{[4
]}

Backhed, Fredrik ^{[7
,11
,12
]}

Prevot, Vincent ^{[6
]}

Marsicano, Giovanni ^{[1
]}

Staels, Bart ^{[4
]}

Schoonjans, Kristina ^{[9
]}

Cota, Daniela ^{[1
]}

机构：

[1] Univ Bordeaux, Neuroctr Magendie, U1215, INSERM, F-3300 Bordeaux, France

[2] Inst Tecnol Super Tacambaro, Lab Neuronutr & Metab Disorders, Tacambaro 61650, Michoacan, Mexico

[3] Univ Fed Pernambuco, Posgrad Neuropsiquiatria & Ciencias Comportamento, BR-50732970 Recife, PE, Brazil

[4] Univ Lille, Inst Pasteur Lille, CHU Lille, INSERM,U1011 EGID, F-59019 Lille, France

[5] Univ Lille, Inst Pasteur Lille, EGID, INSERM,U1177 Drugs & Mol Living Syst, F-59000 Lille, France

[6] Univ Lille, Lab Dev & Plast Neuroendocrine Brain, EGID, Lille Neurosci & Cognit,UMR S1172,INSERM,CHU Lill, F-59000 Lille, France

[7] Univ Gothenburg, Sahlgrenska Acad, Inst Med, Wallenberg Lab,Dept Mol & Clin Med, S-41345 Gothenburg, Sweden

[8] Univ Lille, Inst Pasteur Lille, INSERM, U1177 Drugs & Mol Living Syst, F-59000 Lille, France

[9] Ecole Polytech Fed Lausanne, Inst Bioengn, Fac Life Sci, CH-1015 Lausanne, Switzerland

[10] Univ Lyon 1, INSERM U1213 Nutr Diabet & Brain, Fac Med Lyon Est, F-69372 Lyon, France

[11] Univ Copenhagen, Novo Nordisk Fdn, Fac Hlth Sci, Ctr Basic Metab Res, DK-2200 Copenhagen N, Denmark

[12] Sahlgrens Univ Hosp, Dept Clin Physiol, Reg Vastra Gotaland, Gothenburg, Sweden

来源：

CELL METABOLISM | 2021年 / 33卷 / 07期

基金：

欧洲研究理事会; 瑞士国家科学基金会;

关键词：

ACID RECEPTOR TGR5; ENERGY-EXPENDITURE; GASTRIC BYPASS; GLUCOSE; ACTIVATION; SERUM; THERMOGENESIS; SECRETION; NEURONS; MOUSE;

D O I：

10.1016/j.cmet.2021.04.009

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

摘要：

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.

引用

页码：1483 / +

页数：21

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