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Bone controls browning of white adipose tissue and protects from diet-induced obesity through Schnurri-3-regulated SLIT2 secretion

Author

Listed:
  • Zan Li

    (Xiamen University
    Weill Cornell Medicine
    Central South University
    Zhejiang University School of Medicine)

  • Baohong Shi

    (Xiamen University
    Xiamen University)

  • Na Li

    (Xiamen University
    Weill Cornell Medicine
    Xiamen University)

  • Jun Sun

    (Weill Cornell Medicine)

  • Xiangchen Zeng

    (Xiamen University)

  • Rui Huang

    (Xiamen University)

  • Seoyeon Bok

    (Weill Cornell Medicine)

  • Xiaohui Chen

    (Xiamen University
    Xiamen University)

  • Jie Han

    (Xiamen University)

  • Alisha R. Yallowitz

    (Weill Cornell Medicine)

  • Shawon Debnath

    (Weill Cornell Medicine)

  • Michelle Cung

    (Weill Cornell Medicine)

  • Zheng Ling

    (Weill Cornell Medicine)

  • Chuan-Qi Zhong

    (Xiamen University)

  • Yixang Hong

    (Xiamen University)

  • Gang Li

    (Xiamen University)

  • Mascha Koenen

    (The Rockefeller University)

  • Paul Cohen

    (The Rockefeller University)

  • Xinhui Su

    (Zhejiang University School of Medicine)

  • Hongbin Lu

    (Central South University
    Aging and Regenerative Medicine of Hunan Province
    Central South University)

  • Matthew B. Greenblatt

    (Weill Cornell Medicine
    Hospital for Special Surgery)

  • Ren Xu

    (Xiamen University
    Xiamen University)

Abstract

The skeleton has been suggested to function as an endocrine organ controlling whole organism energy balance, however the mediators of this effect and their molecular links remain unclear. Here, utilizing Schnurri-3−/− (Shn3−/−) mice with augmented osteoblast activity, we show Shn3−/−mice display resistance against diet-induced obesity and enhanced white adipose tissue (WAT) browning. Conditional deletion of Shn3 in osteoblasts but not adipocytes recapitulates lean phenotype of Shn3−/−mice, indicating this phenotype is driven by skeleton. We further demonstrate osteoblasts lacking Shn3 can secrete cytokines to promote WAT browning. Among them, we identify a C-terminal fragment of SLIT2 (SLIT2-C), primarily secreted by osteoblasts, as a Shn3-regulated osteokine that mediates WAT browning. Lastly, AAV-mediated Shn3 silencing phenocopies the lean phenotype and augmented glucose metabolism. Altogether, our findings establish a novel bone-fat signaling axis via SHN3 regulated SLIT2-C production in osteoblasts, offering a potential therapeutic target to address both osteoporosis and metabolic syndrome.

Suggested Citation

  • Zan Li & Baohong Shi & Na Li & Jun Sun & Xiangchen Zeng & Rui Huang & Seoyeon Bok & Xiaohui Chen & Jie Han & Alisha R. Yallowitz & Shawon Debnath & Michelle Cung & Zheng Ling & Chuan-Qi Zhong & Yixang, 2024. "Bone controls browning of white adipose tissue and protects from diet-induced obesity through Schnurri-3-regulated SLIT2 secretion," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-51155-6
    DOI: 10.1038/s41467-024-51155-6
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    References listed on IDEAS

    as
    1. Yeon-Suk Yang & Jun Xie & Dan Wang & Jung-Min Kim & Phillip W. L. Tai & Ellen Gravallese & Guangping Gao & Jae-Hyuck Shim, 2019. "Bone-targeting AAV-mediated silencing of Schnurri-3 prevents bone loss in osteoporosis," Nature Communications, Nature, vol. 10(1), pages 1-13, December.
    2. Ioanna Mosialou & Steven Shikhel & Jian-Min Liu & Antonio Maurizi & Na Luo & Zhenyan He & Yiru Huang & Haihong Zong & Richard A. Friedman & Jonathan Barasch & Patricia Lanzano & Liyong Deng & Rudolph , 2017. "MC4R-dependent suppression of appetite by bone-derived lipocalin 2," Nature, Nature, vol. 543(7645), pages 385-390, March.
    3. Yu-Hua Tseng & Efi Kokkotou & Tim J. Schulz & Tian Lian Huang & Jonathon N. Winnay & Cullen M. Taniguchi & Thien T. Tran & Ryo Suzuki & Daniel O. Espinoza & Yuji Yamamoto & Molly J. Ahrens & Andrew T., 2008. "New role of bone morphogenetic protein 7 in brown adipogenesis and energy expenditure," Nature, Nature, vol. 454(7207), pages 1000-1004, August.
    4. Shawon Debnath & Alisha R. Yallowitz & Jason McCormick & Sarfaraz Lalani & Tuo Zhang & Ren Xu & Na Li & Yifang Liu & Yeon Suk Yang & Mark Eiseman & Jae-Hyuck Shim & Meera Hameed & John H. Healey & Mat, 2018. "Discovery of a periosteal stem cell mediating intramembranous bone formation," Nature, Nature, vol. 562(7725), pages 133-139, October.
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