TGR5 signalling promotes mitochondrial fission and beige remodelling of white adipose tissue
Open Access
- 16 January 2018
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Communications
- Vol. 9 (1), 1-13
- https://doi.org/10.1038/s41467-017-02068-0
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.This publication has 71 references indexed in Scilit:
- Fis1, Mff, MiD49, and MiD51 mediate Drp1 recruitment in mitochondrial fissionMolecular Biology of the Cell, 2013
- Mechanism of Fatty-Acid-Dependent UCP1 Uncoupling in Brown Fat MitochondriaCell, 2012
- TGR5 Activation Inhibits Atherosclerosis by Reducing Macrophage Inflammation and Lipid LoadingCell Metabolism, 2011
- Mff is an essential factor for mitochondrial recruitment of Drp1 during mitochondrial fission in mammalian cellsThe Journal of cell biology, 2010
- TGR5-Mediated Bile Acid Sensing Controls Glucose HomeostasisCell Metabolism, 2009
- Initiation of myoblast to brown fat switch by a PRDM16–C/EBP-β transcriptional complexNature, 2009
- PRDM16 controls a brown fat/skeletal muscle switchNature, 2008
- The Novel Tail-anchored Membrane Protein Mff Controls Mitochondrial and Peroxisomal Fission in Mammalian CellsMolecular Biology of the Cell, 2008
- Transcriptional Control of Brown Fat Determination by PRDM16Cell Metabolism, 2007
- Transcriptional control of adipocyte formationCell Metabolism, 2006