PRDM16 controls a brown fat/skeletal muscle switch

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. Rudnicki, David R. Beier and Bruce M. Spiegelman ()
Additional contact information
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

Nature, 2008, vol. 454, issue 7207, 961-967

Abstract: 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.

Date: 2008
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DOI: 10.1038/nature07182

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