Velazquez-Villegas 2018 Nat Commun

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Velazquez-Villegas LA, Perino A, Lemos V, Zietak M, Nomura M, Pols TWH, Schoonjans K (2018) TGR5 signalling promotes mitochondrial fission and beige remodelling of white adipose tissue. Nat Commun 9:245.

» PMID: 29339725 Open Access

Velazquez-Villegas LA, Perino A, Lemos V, Zietak M, Nomura M, Pols TWH, Schoonjans K (2018) Nat Commun

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.

Bioblast editor: Kandolf G

Labels: MiParea: Respiration, mt-Structure;fission;fusion, nDNA;cell genetics, Genetic knockout;overexpression, Exercise physiology;nutrition;life style 

Organism: Mouse  Tissue;cell: Fat  Preparation: Intact cells 

Coupling state: ROUTINE, ET 

HRR: Oxygraph-2k 

Labels, 2018-03