Short Article Hypothalamic bile acid-TGR5 signaling protects from obesity

Castellanos-Jankiewicz Ashley; Guzman-Quevedo Omar; Fenelon Valerie S.Zizzari PhilippeQuarta CarmeloBellocchio LuigiTailleux AnneCharton JulieFernandois DanielaHenricsson MarcusPiveteau CatherineSimon VincentAllard CamilleQuemener SandrineGuinot ValentineHennuyer NathaliePerino AlessiaDuveau AlexiaMaitre MarleneLeste-Lasserre ThierryClark SamanthaDupuy NathalieCannich AstridGonzales DelphineDeprez BenoitMithieux GillesDombrowicz DavidBackhed FredrikPrevot VincentMarsicano GiovanniStaels BartSchoonjans KristinaCota Daniela

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Short Article Hypothalamic bile acid-TGR5 signaling protects from obesity

机译：Short Article Hypothalamic bile acid-TGR5 signaling protects from obesity

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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.

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《Cell metabolism》 |2021年第7期|1483-1492|共21页
作者
Castellanos-Jankiewicz Ashley; Guzman-Quevedo Omar; Fenelon Valerie S.Zizzari PhilippeQuarta CarmeloBellocchio LuigiTailleux AnneCharton JulieFernandois DanielaHenricsson MarcusPiveteau CatherineSimon VincentAllard CamilleQuemener SandrineGuinot ValentineHennuyer NathaliePerino AlessiaDuveau AlexiaMaitre MarleneLeste-Lasserre ThierryClark SamanthaDupuy NathalieCannich AstridGonzales DelphineDeprez BenoitMithieux GillesDombrowicz DavidBackhed FredrikPrevot VincentMarsicano GiovanniStaels BartSchoonjans KristinaCota Daniela;
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作者单位

Univ Gothenburg, Sahlgrenska Acad, Inst Med, Wallenberg Lab,Dept Mol & Clin Med, S-41345 Gothenburg;

Univ Lille, Lab Dev & Plast Neuroendocrine Brain, EGID, Lille Neurosci & Cognit,UMR S1172,INSERM;

Univ Bordeaux, Neuroctr Magendie, U1215, INSERM, F-3300 Bordeaux, FranceUniv Lille, Inst Pasteur Lille, CHU Lille, INSERM,U1011 EGID, F-59019 Lille, FranceEcole Polytech Fed Lausanne, Inst Bioengn, Fac Life Sci, CH-1015 Lausanne, SwitzerlandUniv Lille, Inst Pasteur Lille, EGID, INSERM,U1177 Drugs & Mol Living Syst, F-59000 Lille, FranceUniv Lille, Inst Pasteur Lille, INSERM, U1177 Drugs & Mol Living Syst, F-59000 Lille, FranceUniv Lyon 1, INSERM U1213 Nutr Diabet & Brain, Fac Med Lyon Est, F-69372 Lyon, France;

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中图分类内分泌腺疾病及代谢病;
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Short Article Hypothalamic bile acid-TGR5 signaling protects from obesity

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