PRDM16 controls a brown fat/skeletal muscle switch

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 myoge...

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Bibliographic Details
Published in:Nature 2008-08, Vol.454 (7207), p.961-967
Main Authors: Seale, Patrick, Bjork, Bryan, Yang, Wenli, Kajimura, Shingo, Chin, Sherry, Kuang, Shihuan, Scimè€, Anthony, Devarakonda, Srikripa, Conroe, Heather M, Erdjument-Bromage, Hediye
Format: Article
Language:English
Subjects:
adipocytes
Adipocytes, Brown - cytology
Adipocytes, Brown - metabolism
Adipocytes, White - metabolism
Adipose Tissue, Brown - cytology
Animals
Biological and medical sciences
Brown adipose tissue
cell differentiation
Cell Differentiation - genetics
Cell Line
Cells
Cercopithecus aethiops
Chemicals
COS Cells
DNA-Binding Proteins - genetics
DNA-Binding Proteins - metabolism
Fundamental and applied biological sciences. Psychology
Gene expression
Gene Expression Regulation, Developmental
genes
Genetic engineering
Genetic regulation
Kinases
Male
Mice
Muscle Development - genetics
Muscle, Skeletal - cytology
Muscle, Skeletal - growth & development
Muscle, Skeletal - metabolism
Muscles
Muscular system
myoblasts
myocytes
Myogenic Regulatory Factor 5 - genetics
Physiological aspects
PPAR gamma - genetics
Prdm16 gene
Rodents
skeletal muscle
Skeletal system
Striated muscle. Tendons
transcription factors
Transcription Factors - genetics
Transcription Factors - metabolism
Vertebrates: osteoarticular system, musculoskeletal system
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Summary: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-gamma (peroxisome-proliferator-activated receptor-gamma) 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.
ISSN:0028-0836
1476-4687
1476-4679
DOI:10.1038/nature07182