Adipose ABHD6 regulates tolerance to cold and thermogenic programs

Pegah Poursharifi, Camille Attané, Yves Mugabo, Anfal Al-Mass, Anindya Ghosh, Clémence Schmitt, Shangang Zhao, Julian Guida, Roxane Lussier, Heidi Erb, Isabelle Chenier, Marie Line Peyot, Erik Joly, Christophe Noll, André C. Carpentier, S. R. Murthy Madiraju, Marc Prentki

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Enhanced energy expenditure in brown (BAT) and white adipose tissues (WAT) can be therapeutic against metabolic diseases. We examined the thermogenic role of adipose α/βhydrolase domain 6 (ABHD6), which hydrolyzes monoacylglycerol (MAG), by employing adipose-specific ABHD6-KO mice. Control and KO mice showed similar phenotypes at room temperature and thermoneutral conditions. However, KO mice were resistant to hypothermia, which can be accounted for by the simultaneously increased lipolysis and lipogenesis of the thermogenic glycerolipid/free fatty acid (GL/FFA) cycle in visceral fat, despite unaltered uncoupling protein 1 expression. Upon cold stress, nuclear 2-MAG levels increased in visceral WAT of the KO mice. Evidence is provided that 2-MAG causes activation of PPARα in white adipocytes, leading to elevated expression and activity of GL/FFA cycle enzymes. In the ABHD6-ablated BAT, glucose and oxidative metabolism were elevated upon cold induction, without changes in GL/FFA cycle and lipid turnover. Moreover, response to in vivo β3-adrenergic stimulation was comparable between KO and control mice. Our data reveal a MAG/PPARα/GL/FFA cycling metabolic signaling network in visceral adipose tissue, which contributes to cold tolerance, and that adipose ABHD6 is a negative modulator of adaptive thermogenesis.

Original languageEnglish (US)
Article numbere140294
JournalJCI Insight
Volume5
Issue number24
DOIs
StatePublished - Dec 17 2020

ASJC Scopus subject areas

  • Medicine(all)

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