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FAK signalling controls insulin sensitivity through regulation of adipocyte survival

Author

Listed:
  • Cynthia T. Luk

    (Toronto General Hospital Research Institute, University Health Network
    Institute of Medical Science, University of Toronto)

  • Sally Yu Shi

    (Toronto General Hospital Research Institute, University Health Network
    Institute of Medical Science, University of Toronto)

  • Erica P. Cai

    (Toronto General Hospital Research Institute, University Health Network
    Institute of Medical Science, University of Toronto)

  • Tharini Sivasubramaniyam

    (Toronto General Hospital Research Institute, University Health Network
    Institute of Medical Science, University of Toronto)

  • Mansa Krishnamurthy

    (Toronto General Hospital Research Institute, University Health Network)

  • Jara J. Brunt

    (Toronto General Hospital Research Institute, University Health Network
    Institute of Medical Science, University of Toronto)

  • Stephanie A. Schroer

    (Toronto General Hospital Research Institute, University Health Network)

  • Daniel A. Winer

    (Toronto General Hospital Research Institute, University Health Network
    University Health Network)

  • Minna Woo

    (Toronto General Hospital Research Institute, University Health Network
    Institute of Medical Science, University of Toronto
    University Health Network, University of Toronto)

Abstract

Focal adhesion kinase (FAK) plays a central role in integrin signalling, which regulates growth and survival of tumours. Here we show that FAK protein levels are increased in adipose tissue of insulin-resistant obese mice and humans. Disruption of adipocyte FAK in mice or in 3T3 L1 cells decreases adipocyte survival. Adipocyte-specific FAK knockout mice display impaired adipose tissue expansion and insulin resistance on prolonged metabolic stress from a high-fat diet or when crossed on an obese db/db or ob/ob genetic background. Treatment of these mice with a PPARγ agonist does not restore adiposity or improve insulin sensitivity. In contrast, inhibition of apoptosis, either genetically or pharmacologically, attenuates adipocyte death, restores normal adiposity and improves insulin sensitivity. Together, these results demonstrate that FAK is required for adipocyte survival and maintenance of insulin sensitivity, particularly in the context of adipose tissue expansion as a result of caloric excess.

Suggested Citation

  • Cynthia T. Luk & Sally Yu Shi & Erica P. Cai & Tharini Sivasubramaniyam & Mansa Krishnamurthy & Jara J. Brunt & Stephanie A. Schroer & Daniel A. Winer & Minna Woo, 2017. "FAK signalling controls insulin sensitivity through regulation of adipocyte survival," Nature Communications, Nature, vol. 8(1), pages 1-13, April.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms14360
    DOI: 10.1038/ncomms14360
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    Cited by:

    1. Cheng Xu & Hongyi Zhou & Yulan Jin & Khushboo Sahay & Anna Robicsek & Yisong Liu & Kunzhe Dong & Jiliang Zhou & Amanda Barrett & Huabo Su & Weiqin Chen, 2022. "Hepatic neddylation deficiency triggers fatal liver injury via inducing NF-κB-inducing kinase in mice," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    2. Jihoon Shin & Shinichiro Toyoda & Yosuke Okuno & Reiko Hayashi & Shigeki Nishitani & Toshiharu Onodera & Haruyo Sakamoto & Shinya Ito & Sachiko Kobayashi & Hirofumi Nagao & Shunbun Kita & Michio Otsuk, 2023. "HSP47 levels determine the degree of body adiposity," Nature Communications, Nature, vol. 14(1), pages 1-14, December.

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