α/β-Hydrolase Domain 6 Deletion Induces Adipose Browning and Prevents Obesity and Type 2 Diabetes

Autor: Shangang Zhao, Yves Mugabo, Gwynne Ballentine, Camille Attane, Jose Iglesias, Pegah Poursharifi, Dongwei Zhang, Thuy Anne Nguyen, Heidi Erb, Raphael Prentki, Marie-Line Peyot, Erik Joly, Stephanie Tobin, Stephanie Fulton, J. Mark Brown, S.R. Murthy Madiraju, Marc Prentki
Jazyk: angličtina
Rok vydání: 2016
Předmět:
Zdroj: Cell Reports, Vol 14, Iss 12, Pp 2872-2888 (2016)
Druh dokumentu: article
ISSN: 2211-1247
DOI: 10.1016/j.celrep.2016.02.076
Popis: Suppression of α/β-domain hydrolase-6 (ABHD6), a monoacylglycerol (MAG) hydrolase, promotes glucose-stimulated insulin secretion by pancreatic β cells. We report here that high-fat-diet-fed ABHD6-KO mice show modestly reduced food intake, decreased body weight gain and glycemia, improved glucose tolerance and insulin sensitivity, and enhanced locomotor activity. ABHD6-KO mice also show increased energy expenditure, cold-induced thermogenesis, brown adipose UCP1 expression, fatty acid oxidation, and white adipose browning. Adipose browning and cold-induced thermogenesis are replicated by the ABHD6 inhibitor WWL70 and by antisense oligonucleotides targeting ABHD6. Our evidence suggests that one mechanism by which the lipolysis derived 1-MAG signals intrinsic and cell-autonomous adipose browning is via PPARα and PPARγ activation, and that ABHD6 regulates adipose browning by controlling signal competent 1-MAG levels. Thus, ABHD6 regulates energy homeostasis, brown adipose function, and white adipose browning and is a potential therapeutic target for obesity and type 2 diabetes.
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