期刊
Cell Metabolism
卷 24, 期 6, 页码 835-847出版社
CELL PRESS
DOI: 10.1016/j.cmet.2016.10.005
关键词
-
资金
- NIH [DK098830, DK102199, T32DK007201]
- Boston Nutrition Obesity Research Center [P30 DK046200]
- CTSA grant [1UL1TR001430]
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 PPAR gamma regulate select adipocyte programs. Deacetylation of K268 and K293 in the ligand-binding domain of PPAR gamma by Sirt1 induces browning of WAT. Phosphorylation of S273 of PPAR gamma 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.
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