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PRDM16 controls a brown fat/skeletal muscle switch

Author

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  • Patrick Seale

    (Harvard Medical School, 1 Jimmy Fund Way, Boston, Massachusetts 02115, USA)

  • Bryan Bjork

    (Brigham and Women’s Hospital, Harvard Medical School, New Research Building, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA)

  • Wenli Yang

    (Harvard Medical School, 1 Jimmy Fund Way, Boston, Massachusetts 02115, USA)

  • Shingo Kajimura

    (Harvard Medical School, 1 Jimmy Fund Way, Boston, Massachusetts 02115, USA)

  • Sherry Chin

    (Harvard Medical School, 1 Jimmy Fund Way, Boston, Massachusetts 02115, USA)

  • Shihuan Kuang

    (The Sprott Center for Stem Cell Research, Ottawa Health Research Institute, Molecular Medicine Program, 501 Smyth Road, Ottawa, Ontario K1H 8L6, Canada)

  • Anthony Scimè

    (The Sprott Center for Stem Cell Research, Ottawa Health Research Institute, Molecular Medicine Program, 501 Smyth Road, Ottawa, Ontario K1H 8L6, Canada)

  • Srikripa Devarakonda

    (Harvard Medical School, 1 Jimmy Fund Way, Boston, Massachusetts 02115, USA)

  • Heather M. Conroe

    (Harvard Medical School, 1 Jimmy Fund Way, Boston, Massachusetts 02115, USA)

  • Hediye Erdjument-Bromage

    (Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA)

  • Paul Tempst

    (Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA)

  • Michael A. Rudnicki

    (The Sprott Center for Stem Cell Research, Ottawa Health Research Institute, Molecular Medicine Program, 501 Smyth Road, Ottawa, Ontario K1H 8L6, Canada)

  • David R. Beier

    (Brigham and Women’s Hospital, Harvard Medical School, New Research Building, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA)

  • Bruce M. Spiegelman

    (Harvard Medical School, 1 Jimmy Fund Way, Boston, Massachusetts 02115, USA)

Abstract

Brown fat can increase energy expenditure and protect against obesity through a specialized program of uncoupled respiration. Here we show by in vivo fate mapping that brown, but not white, fat cells arise from precursors that express Myf5, a gene previously thought to be expressed only in the myogenic lineage. We also demonstrate that the transcriptional regulator PRDM16 (PRD1-BF1-RIZ1 homologous domain containing 16) controls a bidirectional cell fate switch between skeletal myoblasts and brown fat cells. Loss of PRDM16 from brown fat precursors causes a loss of brown fat characteristics and promotes muscle differentiation. Conversely, ectopic expression of PRDM16 in myoblasts induces their differentiation into brown fat cells. PRDM16 stimulates brown adipogenesis by binding to PPAR-γ (peroxisome-proliferator-activated receptor-γ) and activating its transcriptional function. Finally, Prdm16-deficient brown fat displays an abnormal morphology, reduced thermogenic gene expression and elevated expression of muscle-specific genes. Taken together, these data indicate that PRDM16 specifies the brown fat lineage from a progenitor that expresses myoblast markers and is not involved in white adipogenesis.

Suggested Citation

  • Patrick Seale & Bryan Bjork & Wenli Yang & Shingo Kajimura & Sherry Chin & Shihuan Kuang & Anthony Scimè & Srikripa Devarakonda & Heather M. Conroe & Hediye Erdjument-Bromage & Paul Tempst & Michael A, 2008. "PRDM16 controls a brown fat/skeletal muscle switch," Nature, Nature, vol. 454(7207), pages 961-967, August.
    • Handle: RePEc:nat:nature:v:454:y:2008:i:7207:d:10.1038_nature07182
    DOI: 10.1038/nature07182
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    Cited by:

    1. Xun Huang & Xinmeng Li & Hongyu Shen & Yiheng Zhao & Zhao Zhou & Yushuang Wang & Jingfei Yao & Kaili Xue & Dongmei Wu & Yifu Qiu, 2023. "Transcriptional repression of beige fat innervation via a YAP/TAZ-S100B axis," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    2. Fenfen Li & Jia Jing & Miranda Movahed & Xin Cui & Qiang Cao & Rui Wu & Ziyue Chen & Liqing Yu & Yi Pan & Huidong Shi & Hang Shi & Bingzhong Xue, 2021. "Epigenetic interaction between UTX and DNMT1 regulates diet-induced myogenic remodeling in brown fat," Nature Communications, Nature, vol. 12(1), pages 1-22, December.
    3. Yan-Ting Chen & Qi-Yuan Yang & Yun Hu & Xiang-Dong Liu & Jeanene M. Avila & Mei-Jun Zhu & Peter W. Nathanielsz & Min Du, 2021. "Imprinted lncRNA Dio3os preprograms intergenerational brown fat development and obesity resistance," Nature Communications, Nature, vol. 12(1), pages 1-18, December.
    4. Yusuke Adachi & Kazutaka Ueda & Seitaro Nomura & Kaoru Ito & Manami Katoh & Mikako Katagiri & Shintaro Yamada & Masaki Hashimoto & Bowen Zhai & Genri Numata & Akira Otani & Munetoshi Hinata & Yuta Hir, 2022. "Beiging of perivascular adipose tissue regulates its inflammation and vascular remodeling," Nature Communications, Nature, vol. 13(1), pages 1-14, December.

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