title: Browning of White Adipose Tissue with Roscovitine Induces a Distinct Population of UCP1+Adipocytes.
abstract: Brown-like adipocytes exist in several adipose depots including white (WAT) as well as brown (BAT). Activation of these UCP1+cells is a potential therapeutic strategy to combat obesity. Studies have shown that posttranslational modifications of PPARγ regulate select adipocyte programs. Deacetylation of K268 and K293 in the ligand-binding domain of PPARγ by Sirt1 induces browning of WAT. Phosphorylation of S273 of PPARγ by CDK5 or ERK stimulates a diabetogenic program of gene expression in WAT. Here, we report that roscovitine, a CDK inhibitor, prevents S273 phosphorylation and promotes formation of UCP1+(brite) adipocytes in WAT. It also enhances energy expenditure as well as prevents diet-induced obesity and insulin resistance. Analysis of fluorescence-activated cell-sorted UCP1+adipocytes shows that the mRNA signature of brite adipocytes is distinct from beige adipocytes, which arise through catecholamine signaling. These results suggest that brown-like adipocytes in WAT may arise from multiple origins.
authors.affiliation: Department of Biochemistry, Boston University School of Medicine, Boston, MA 02118, USA.
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Biochemistry, Boston University School of Medicine, Boston, MA 02118, USA.
authors.forename: Libin
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Biochemistry, Boston University School of Medicine, Boston, MA 02118, USA.
authors.forename: Jean Z
authors.initials: JZ
authors.lastname: Lin
authors.affiliation: Renal Section, Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA.
authors.forename: Tamar R
authors.initials: TR
authors.lastname: Aprahamian
authors.affiliation: Department of Biochemistry, Boston University School of Medicine, Boston, MA 02118, USA. Electronic address: sfarmer@bu.edu.
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Farmer
mesh_terms: D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism*; D002001:Adipose Tissue, Brown / Q000187:drug effects / Q000378:metabolism*; D052436:Adipose Tissue, White / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D004032:Diet; D004734:Energy Metabolism / Q000187:drug effects; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000187:drug effects; D016678:Genome; D018149:Glucose Intolerance / Q000378:metabolism / Q000473:pathology; D007333:Insulin Resistance; D008297:Male; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000378:metabolism / Q000473:pathology; D047495:PPAR gamma / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D020011:Protective Agents / Q000494:pharmacology; D011687:Purines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D000077546:Roscovitine; D012694:Serine / Q000378:metabolism; D022722:Thermogenesis / Q000187:drug effects; D000071256:Uncoupling Protein 1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D047495:PPAR gamma; D020011:Protective Agents; D011687:Purines; D012333:RNA, Messenger; D000071256:Uncoupling Protein 1; D000077546:Roscovitine; D012694:Serine