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

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.
• Subjects:
  Adipocytes Adipose Tissue, Brown Adipose Tissue, White Animals Article Diet Energy Metabolism Flow Cytometry Gene Expression Regulation Genome Glucose Intolerance Insulin Resistance Male Mice, Inbred C57BL Obesity Phosphorylation PPAR Gamma Protective Agents Purines RNA, Messenger Roscovitine Serine Thermogenesis Uncoupling Protein 1

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• Source:
  Cell Metab. 24(6):835-847
• 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 ; R01 DK102199/NIDDK NIH HHS/National Institute of Diabetes and Digestive and Kidney Diseases/United States ; UL1 TR001430/NCATS NIH HHS/National Center for Advancing Translational Sciences/United States
• Volume:
  24
• Issue:
  6
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:4edf7f0ea8a0f1b25d9a6b7ca1641231ffbd1fd6eb1a8477b5a21aa1d753f0e6
• Download URL:
  https://stacks.cdc.gov/view/cdc/80391/cdc_80391_DS1.pdf
• File Type:
  [PDF - 1.16 MB ]