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Browning of White Adipose Tissue with Roscovitine Induces a Distinct Population of UCP1+ Adipocytes
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December 13 2016
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Source: Cell Metab. 24(6):835-847
[PDF-1.16 MB]
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Alternative Title:Cell Metab
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Description: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.
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Pubmed ID:27974179
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Pubmed Central ID:PMC6674884
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Funding:R01 DK098830/NIDDK NIH HHS/National Institute of Diabetes and Digestive and Kidney Diseases/United States ; T32 DK007201/NIDDK NIH HHS/National Institute of Diabetes and Digestive and Kidney Diseases/United States ; S10 OD021652/ODCDC CDC HHS/Office of the Director/United States ; P30 DK046200/NIDDK NIH HHS/National Institute of Diabetes and Digestive and Kidney Diseases/United States ; F32 DK109635/NIDDK NIH HHS/National Institute of Diabetes and Digestive and Kidney Diseases/United States ; ... More +
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Volume:24
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Issue:6
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