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Senescence-associated 13-HODE production promotes age-related liver steatosis by directly inhibiting catalase activity

Author

Listed:
  • Jinjie Duan

    (Tianjin Medical University
    Tianjin Medical University
    Tianjin Medical University)

  • Wenhui Dong

    (Tianjin Medical University
    Tianjin Medical University)

  • Guangyan Wang

    (Tianjin Medical University
    Tianjin Medical University
    Tianjin Medical University)

  • Wenjing Xiu

    (Tianjin Medical University
    Tianjin Medical University)

  • Guangyin Pu

    (Tianjin Medical University
    Tianjin Medical University)

  • Jingwen Xu

    (Tianjin Medical University
    Tianjin Medical University)

  • Chenji Ye

    (Xinxiang Medical University)

  • Xu Zhang

    (Tianjin Medical University)

  • Yi Zhu

    (Tianjin Medical University
    Tianjin Medical University)

  • Chunjiong Wang

    (Tianjin Medical University
    Tianjin Medical University
    Tianjin Medical University)

Abstract

Aging is a major risk factor for metabolic disorders. Polyunsaturated fatty acid-derived bioactive lipids play critical roles as signaling molecules in metabolic processes. Nonetheless, their effects on age-related liver steatosis remain unknown. Here we show that senescent liver cells induce liver steatosis in a paracrine manner. Linoleic acid-derived 9-hydroxy-octadecadienoic acid (9-HODE) and 13-HODE increase in middle-aged (12-month-old) and aged (20-month-old) male mouse livers and conditioned medium from senescent hepatocytes and macrophages. Arachidonate 15-lipoxygenase, an enzyme for 13-HODE and 9-HODE production, is upregulated in senescent cells. A 9-HODE and 13-HODE mixture induces liver steatosis and activates SREBP1. Furthermore, catalase (CAT) is a direct target of 13-HODE, and its activity is decreased by 13-HODE. CAT overexpression reduces 13-HODE-induced liver steatosis and protects male mice against age-related liver steatosis. Therefore, 13-HODE produced by senescent hepatocytes and macrophages activates SREBP1 by directly inhibiting CAT activity and promotes liver steatosis.

Suggested Citation

  • Jinjie Duan & Wenhui Dong & Guangyan Wang & Wenjing Xiu & Guangyin Pu & Jingwen Xu & Chenji Ye & Xu Zhang & Yi Zhu & Chunjiong Wang, 2023. "Senescence-associated 13-HODE production promotes age-related liver steatosis by directly inhibiting catalase activity," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-44026-z
    DOI: 10.1038/s41467-023-44026-z
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    References listed on IDEAS

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    1. Mikolaj Ogrodnik & Satomi Miwa & Tamar Tchkonia & Dina Tiniakos & Caroline L. Wilson & Albert Lahat & Christoper P. Day & Alastair Burt & Allyson Palmer & Quentin M. Anstee & Sushma Nagaraja Grellsche, 2017. "Cellular senescence drives age-dependent hepatic steatosis," Nature Communications, Nature, vol. 8(1), pages 1-12, August.
    2. Judith Campisi & Pankaj Kapahi & Gordon J. Lithgow & Simon Melov & John C. Newman & Eric Verdin, 2019. "From discoveries in ageing research to therapeutics for healthy ageing," Nature, Nature, vol. 571(7764), pages 183-192, July.
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