期刊
NATURE COMMUNICATIONS
卷 9, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41467-017-02068-0
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资金
- Swiss National Science Foundation SNSF [31003A_ 125487]
- Ecole Polytechnique Federale de Lausanne (EPFL)
- CONACYT [263859]
- Foundation for Health and Education
- KNOW consortium 'Healthy Animal-Safe Food' MSHE [05-1/KNOW2/2015]
- Foundation for Polish Science
- Portuguese Foundation for Science and Technology through the Graduate Program in Basic and Applied Biology (GABBA) PhD program [SFRH/BD/52046/2012]
- Fundação para a Ciência e a Tecnologia [SFRH/BD/52046/2012] Funding Source: FCT
- Swiss National Science Foundation (SNF) [31003A_125487] Funding Source: Swiss National Science Foundation (SNF)
Remodelling of energy storing white fat into energy expending beige fat could be a promising strategy to reduce adiposity. Here, we show that the bile acid-responsive membrane receptor TGR5 mediates beiging of the subcutaneous white adipose tissue (scWAT) under multiple environmental cues including cold exposure and prolonged high-fat diet feeding. Moreover, administration of TGR5-selective bile acid mimetics to thermoneutral housed mice leads to the appearance of beige adipocyte markers and increases mitochondrial content in the scWAT of Tgr5(+/+) mice but not in their Tgr5(-/-) littermates. This phenotype is recapitulated in vitro in differentiated adipocytes, in which TGR5 activation increases free fatty acid availability through lipolysis, hence fuelling beta-oxidation and thermogenic activity. TGR5 signalling also induces mitochondrial fission through the ERK/DRP1 pathway, further improving mitochondrial respiration. Taken together, these data identify TGR5 as a druggable target to promote beiging with potential applications in the management of metabolic disorders.
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