Browning of White Adipose Tissue with Roscovitine Induces a Distinct Population of UCP1+ Adipocytes

Wang, Hong; Liu, Libin; Lin, Jean Z.; Aprahamian, Tamar R.; Farmer, Stephen R.

doi:10.1016/j.cmet.2016.10.005

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Browning of White Adipose Tissue with Roscovitine Induces a Distinct Population of UCP1+ Adipocytes

Published Date:

December 13 2016

Publisher's site:

http://dx.doi.org/10.1016/j.cmet.2016.10.005 New Site Icon

Source:

Cell Metab. 24(6):835-847

Language:

English

[PDF-1.16 MB]

Details:

Alternative Title:

Cell Metab

Personal Author:

Wang, Hong ; Liu, Libin ; Lin, Jean Z. ; Aprahamian, Tamar R. ; Farmer, Stephen R. ;

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.

Subject:

[+]

Pubmed ID:

27974179

Pubmed Central ID:

PMC6674884

Document Type:

Journal Article

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 ▼

Collection(s):

CDC Public Access

Main Document Checksum:

[+]

Supporting Files:

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