[HTML][HTML] TGR5 signalling promotes mitochondrial fission and beige remodelling of white adipose tissue
LA Velazquez-Villegas, A Perino, V Lemos… - Nature …, 2018 - nature.com
LA Velazquez-Villegas, A Perino, V Lemos, M Zietak, M Nomura, TWH Pols, K Schoonjans
Nature communications, 2018•nature.comRemodelling 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 …
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 …
Abstract
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 β-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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