TY - JOUR
T1 - Adipose ABHD6 regulates tolerance to cold and thermogenic programs
AU - Poursharifi, Pegah
AU - Attané, Camille
AU - Mugabo, Yves
AU - Al-Mass, Anfal
AU - Ghosh, Anindya
AU - Schmitt, Clémence
AU - Zhao, Shangang
AU - Guida, Julian
AU - Lussier, Roxane
AU - Erb, Heidi
AU - Chenier, Isabelle
AU - Peyot, Marie Line
AU - Joly, Erik
AU - Noll, Christophe
AU - Carpentier, André C.
AU - Murthy Madiraju, S. R.
AU - Prentki, Marc
N1 - Publisher Copyright:
Copyright: © 2020, Poursharifi et al. This is an open access article published under the terms of the Creative Commons Attribution 4.0 International License.
PY - 2020/12/17
Y1 - 2020/12/17
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85097806455&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85097806455&partnerID=8YFLogxK
U2 - 10.1172/jci.insight.140294
DO - 10.1172/jci.insight.140294
M3 - Article
C2 - 33201859
AN - SCOPUS:85097806455
SN - 2379-3708
VL - 5
JO - JCI Insight
JF - JCI Insight
IS - 24
M1 - e140294
ER -