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

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

Research output: Contribution to journalArticlepeer-review

51 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2872-2888
Number of pages17
JournalCell Reports
Volume14
Issue number12
DOIs
StatePublished - Mar 29 2016
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Fingerprint

Dive into the research topics of 'α/β-Hydrolase Domain 6 Deletion Induces Adipose Browning and Prevents Obesity and Type 2 Diabetes'. Together they form a unique fingerprint.

Cite this