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Linker histone variant H1.2 is a brake on white adipose tissue browning

Author

Listed:
  • Yangmian Yuan

    (Wuhan University)

  • Yu Fan

    (Wuhan University)

  • Yihao Zhou

    (Wuhan University)

  • Rong Qiu

    (Wuhan University)

  • Wei Kang

    (Wuhan University)

  • Yu Liu

    (Wuhan University)

  • Yuchen Chen

    (Huazhong University of Science and Technology)

  • Chenyu Wang

    (Wuhan University)

  • Jiajian Shi

    (Huazhong University of Science and Technology)

  • Chengyu Liu

    (Huazhong University of Science and Technology)

  • Yangkai Li

    (Huazhong University of Science and Technology)

  • Min Wu

    (Wuhan University)

  • Kun Huang

    (Huazhong University of Science and Technology)

  • Yong Liu

    (Wuhan University)

  • Ling Zheng

    (Wuhan University)

Abstract

Adipose-tissue is a central metabolic organ for whole-body energy homeostasis. Here, we find that highly expressed H1.2, a linker histone variant, senses thermogenic stimuli in beige and brown adipocytes. Adipocyte H1.2 regulates thermogenic genes in inguinal white-adipose-tissue (iWAT) and affects energy expenditure. Adipocyte H1.2 deletion (H1.2AKO) male mice show promoted iWAT browning and improved cold tolerance; while overexpressing H1.2 shows opposite effects. Mechanistically, H1.2 binds to the promoter of Il10rα, which encodes an Il10 receptor, and positively regulates its expression to suppress thermogenesis in a beige cell autonomous manner. Il10rα overexpression in iWAT negates cold-enhanced browning of H1.2AKO male mice. Increased H1.2 level is also found in WAT of obese humans and male mice. H1.2AKO male mice show alleviated fat accumulation and glucose intolerance in long-term normal chow-fed and high fat diet-fed conditions; while Il10rα overexpression abolishes these effects. Here, we show a metabolic function of H1.2-Il10rα axis in iWAT.

Suggested Citation

  • Yangmian Yuan & Yu Fan & Yihao Zhou & Rong Qiu & Wei Kang & Yu Liu & Yuchen Chen & Chenyu Wang & Jiajian Shi & Chengyu Liu & Yangkai Li & Min Wu & Kun Huang & Yong Liu & Ling Zheng, 2023. "Linker histone variant H1.2 is a brake on white adipose tissue browning," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-39713-w
    DOI: 10.1038/s41467-023-39713-w
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    References listed on IDEAS

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