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A brown fat-enriched adipokine Adissp controls adipose thermogenesis and glucose homeostasis

Author

Listed:
  • Qingbo Chen

    (University of Massachusetts Chan Medical School)

  • Lei Huang

    (University of Massachusetts Chan Medical School)

  • Dongning Pan

    (University of Massachusetts Chan Medical School
    Fudan University Shanghai Medical College)

  • Kai Hu

    (University of Massachusetts Chan Medical School)

  • Rui Li

    (University of Massachusetts Chan Medical School)

  • Randall H. Friedline

    (University of Massachusetts Chan Medical School)

  • Jason K. Kim

    (University of Massachusetts Chan Medical School)

  • Lihua Julie Zhu

    (University of Massachusetts Chan Medical School)

  • David A. Guertin

    (University of Massachusetts Chan Medical School)

  • Yong-Xu Wang

    (University of Massachusetts Chan Medical School)

Abstract

The signaling mechanisms underlying adipose thermogenesis have not been fully elucidated. Particularly, the involvement of adipokines that are selectively expressed in brown adipose tissue (BAT) and beige adipocytes remains to be investigated. Here we show that a previously uncharacterized adipokine (UPF0687 protein / human C20orf27 homolog) we named as Adissp (Adipose-secreted signaling protein) is a key regulator for white adipose tissue (WAT) thermogenesis and glucose homeostasis. Adissp expression is adipose-specific and highly BAT-enriched, and its secretion is stimulated by β3-adrenergic activation. Gain-of-functional studies collectively showed that secreted Adissp promotes WAT thermogenesis, improves glucose homeostasis, and protects against obesity. Adipose-specific Adissp knockout mice are defective in WAT browning, and are susceptible to high fat diet-induced obesity and hyperglycemia. Mechanistically, Adissp binds to a putative receptor on adipocyte surface and activates protein kinase A independently of β-adrenergic signaling. These results establish BAT-enriched Adissp as a major upstream signaling component in thermogenesis and offer a potential avenue for the treatment of obesity and diabetes.

Suggested Citation

  • Qingbo Chen & Lei Huang & Dongning Pan & Kai Hu & Rui Li & Randall H. Friedline & Jason K. Kim & Lihua Julie Zhu & David A. Guertin & Yong-Xu Wang, 2022. "A brown fat-enriched adipokine Adissp controls adipose thermogenesis and glucose homeostasis," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-35335-w
    DOI: 10.1038/s41467-022-35335-w
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    References listed on IDEAS

    as
    1. Dongning Pan & Chunxiao Mao & Brian Quattrochi & Randall H. Friedline & Lihua J. Zhu & Dae Young Jung & Jason K. Kim & Brian Lewis & Yong-Xu Wang, 2014. "MicroRNA-378 controls classical brown fat expansion to counteract obesity," Nature Communications, Nature, vol. 5(1), pages 1-12, December.
    2. Omer Keinan & Joseph M. Valentine & Haopeng Xiao & Sushil K. Mahata & Shannon M. Reilly & Mohammad Abu-Odeh & Julia H. Deluca & Benyamin Dadpey & Leslie Cho & Austin Pan & Ruth T. Yu & Yang Dai & Chri, 2021. "Glycogen metabolism links glucose homeostasis to thermogenesis in adipocytes," Nature, Nature, vol. 599(7884), pages 296-301, November.
    3. Yong Chen & Kenji Ikeda & Takeshi Yoneshiro & Annarita Scaramozza & Kazuki Tajima & Qiang Wang & Kyeongkyu Kim & Kosaku Shinoda & Carlos Henrique Sponton & Zachary Brown & Andrew Brack & Shingo Kajimu, 2019. "Thermal stress induces glycolytic beige fat formation via a myogenic state," Nature, Nature, vol. 565(7738), pages 180-185, January.
    4. Lei Huang & Dongning Pan & Qingbo Chen & Lihua J. Zhu & Jianhong Ou & Martin Wabitsch & Yong-Xu Wang, 2017. "Transcription factor Hlx controls a systematic switch from white to brown fat through Prdm16-mediated co-activation," Nature Communications, Nature, vol. 8(1), pages 1-16, December.
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