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CDK6 inhibits white to beige fat transition by suppressing RUNX1

Author

Listed:
  • Xiaoli Hou

    (Tufts Medical Center
    Center for Analysis and Testing)

  • Yongzhao Zhang

    (Tufts Medical Center)

  • Wei Li

    (Tufts Medical Center
    Key Laboratory of Cancer Prevention and Therapy)

  • Alexander J. Hu

    (Tufts Medical Center)

  • Chi Luo

    (Harvard Medical School)

  • Wenhui Zhou

    (Tufts Medical Center)

  • Jamie K. Hu

    (Tufts Medical Center
    MD program for Jamie K. Hu, MD-PhD Program for Stefano G. Daniele)

  • Stefano G. Daniele

    (MD program for Jamie K. Hu, MD-PhD Program for Stefano G. Daniele)

  • Jinfeng Wang

    (Tufts Medical Center
    Linyi People’s Hospital)

  • Jinghao Sheng

    (Tufts Medical Center
    Zhejiang University)

  • Yongsheng Fan

    (Center for Analysis and Testing)

  • Andrew S. Greenberg

    (JM-USDA Human Nutrition Research Center)

  • Stephen R. Farmer

    (Department of Biochemistry)

  • Miaofen G. Hu

    (Tufts Medical Center)

Abstract

Whereas white adipose tissue depots contribute to the development of metabolic diseases, brown and beige adipose tissue has beneficial metabolic effects. Here we show that CDK6 regulates beige adipocyte formation. We demonstrate that mice lacking the CDK6 protein or its kinase domain (K43M) exhibit significant increases beige cell formation, enhanced energy expenditure, better glucose tolerance, and improved insulin sensitivity, and are more resistant to high-fat diet-induced obesity. Re-expression of CDK6 in Cdk6 −/− mature or precursor cells, or ablation of RUNX1 in K43M mature or precursor cells, reverses these phenotypes. Furthermore, RUNX1 positively regulates the expression of Ucp-1 and Pgc1α by binding to proximal promoter regions. Our findings indicate that CDK6 kinase activity negatively regulates the conversion of fat-storing cells into fat-burning cells by suppressing RUNX1, and suggest that CDK6 may be a therapeutic target for the treatment of obesity and related metabolic diseases.

Suggested Citation

  • Xiaoli Hou & Yongzhao Zhang & Wei Li & Alexander J. Hu & Chi Luo & Wenhui Zhou & Jamie K. Hu & Stefano G. Daniele & Jinfeng Wang & Jinghao Sheng & Yongsheng Fan & Andrew S. Greenberg & Stephen R. Farm, 2018. "CDK6 inhibits white to beige fat transition by suppressing RUNX1," Nature Communications, Nature, vol. 9(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-03451-1
    DOI: 10.1038/s41467-018-03451-1
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    Cited by:

    1. Weiqin Yin & Praveen Kumar Rajvanshi & Heather M. Rogers & Teruhiko Yoshida & Jeffrey B. Kopp & Xiuli An & Max Gassmann & Constance T. Noguchi, 2024. "Erythropoietin regulates energy metabolism through EPO-EpoR-RUNX1 axis," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    2. Liam McAllan & Damir Baranasic & Sergio Villicaña & Scarlett Brown & Weihua Zhang & Benjamin Lehne & Marco Adamo & Andrew Jenkinson & Mohamed Elkalaawy & Borzoueh Mohammadi & Majid Hashemi & Nadia Fer, 2023. "Integrative genomic analyses in adipocytes implicate DNA methylation in human obesity and diabetes," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    3. Alexander J. Hu & Wei Li & Calvin Dinh & Yongzhao Zhang & Jamie K. Hu & Stefano G. Daniele & Xiaoli Hou & Zixuan Yang & John M. Asara & Guo-fu Hu & Stephen R. Farmer & Miaofen G. Hu, 2024. "CDK6 inhibits de novo lipogenesis in white adipose tissues but not in the liver," Nature Communications, Nature, vol. 15(1), pages 1-16, December.

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