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ASK1 inhibits browning of white adipose tissue in obesity

Author

Listed:
  • Fabrizio C. Lucchini

    (University Children’s Hospital
    University Children’s Hospital
    University of Zurich)

  • Stephan Wueest

    (University Children’s Hospital
    University Children’s Hospital)

  • Tenagne D. Challa

    (University Children’s Hospital
    University Children’s Hospital)

  • Flurin Item

    (University Children’s Hospital
    University Children’s Hospital)

  • Salvatore Modica

    (ETH Zurich)

  • Marcela Borsigova

    (University Children’s Hospital
    University Children’s Hospital)

  • Yulia Haim

    (Ben-Gurion University of the Negev
    Ben-Gurion University of the Negev)

  • Christian Wolfrum

    (ETH Zurich)

  • Assaf Rudich

    (Ben-Gurion University of the Negev
    Ben-Gurion University of the Negev)

  • Daniel Konrad

    (University Children’s Hospital
    University Children’s Hospital
    University of Zurich)

Abstract

Increasing energy expenditure via induction of adipose tissue browning has become an appealing strategy to treat obesity and associated metabolic complications. Herein, we identify adipocyte-expressed apoptosis signal-regulating kinase 1 (ASK1) as regulator of adipose tissue browning. High fat diet-fed adipocyte-specific ASK1 knockout mice reveal increased UCP1 protein levels in inguinal adipose tissue concomitant with elevated energy expenditure, reduced obesity and ameliorated glucose tolerance compared to control littermates. In addition, ASK1-depletion blunts LPS-mediated downregulation of isoproterenol-induced UCP1 in subcutaneous fat both in vitro and in vivo. Conversely, adipocyte-specific ASK1 overexpression in chow-fed mice attenuates cold-induced UCP1 protein levels in inguinal fat. Mechanistically, ASK1 phosphorylates interferon regulatory factor 3 (IRF3) resulting in reduced Ucp1 expression. Taken together, our studies unravel a role of ASK1 in mediating the inhibitory effect of caloric surplus or LPS-treatment on adipose tissue browning. Adipocyte ASK1 might be a pharmacological target to combat obesity and associated morbidities.

Suggested Citation

  • Fabrizio C. Lucchini & Stephan Wueest & Tenagne D. Challa & Flurin Item & Salvatore Modica & Marcela Borsigova & Yulia Haim & Christian Wolfrum & Assaf Rudich & Daniel Konrad, 2020. "ASK1 inhibits browning of white adipose tissue in obesity," Nature Communications, Nature, vol. 11(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-15483-7
    DOI: 10.1038/s41467-020-15483-7
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    Cited by:

    1. Hongrui Wang & Liang Yu & Jin’e Wang & Yaqing Zhang & Mengchen Xu & Cheng Lv & Bing Cui & Mengmeng Yuan & Yu Zhang & Yupeng Yan & Rutai Hui & Yibo Wang, 2023. "SLC35D3 promotes white adipose tissue browning to ameliorate obesity by NOTCH signaling," Nature Communications, Nature, vol. 14(1), pages 1-19, December.

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