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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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| Published in: | Nature 2008-08, Vol.454 (7207), p.961-967 |
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| Main Authors: | , , , , , , , , , |
| Format: | Article |
| Language: | English |
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| cited_by | cdi_FETCH-LOGICAL-c727t-71bc5672677247b034af30308b58b82d9a8bd7490355c0a487e23142fbca69293 |
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| cites | cdi_FETCH-LOGICAL-c727t-71bc5672677247b034af30308b58b82d9a8bd7490355c0a487e23142fbca69293 |
| container_end_page | 967 |
| container_issue | 7207 |
| container_start_page | 961 |
| container_title | Nature |
| container_volume | 454 |
| creator | Seale, Patrick Bjork, Bryan Yang, Wenli Kajimura, Shingo Chin, Sherry Kuang, Shihuan Scimè, Anthony Devarakonda, Srikripa Conroe, Heather M Erdjument-Bromage, Hediye |
| description | 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. |
| doi_str_mv | 10.1038/nature07182 |
| format | article |
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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.</description><identifier>ISSN: 0028-0836</identifier><identifier>EISSN: 1476-4687</identifier><identifier>EISSN: 1476-4679</identifier><identifier>DOI: 10.1038/nature07182</identifier><identifier>PMID: 18719582</identifier><identifier>CODEN: NATUAS</identifier><language>eng</language><publisher>London: Nature Publishing Group</publisher><subject>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</subject><ispartof>Nature, 2008-08, Vol.454 (7207), p.961-967</ispartof><rights>2009 INIST-CNRS</rights><rights>COPYRIGHT 2008 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Aug 21, 2008</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c727t-71bc5672677247b034af30308b58b82d9a8bd7490355c0a487e23142fbca69293</citedby><cites>FETCH-LOGICAL-c727t-71bc5672677247b034af30308b58b82d9a8bd7490355c0a487e23142fbca69293</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,315,786,790,891,2744,27957,27958</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=20577403$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18719582$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Seale, Patrick</creatorcontrib><creatorcontrib>Bjork, Bryan</creatorcontrib><creatorcontrib>Yang, Wenli</creatorcontrib><creatorcontrib>Kajimura, Shingo</creatorcontrib><creatorcontrib>Chin, Sherry</creatorcontrib><creatorcontrib>Kuang, Shihuan</creatorcontrib><creatorcontrib>Scimè, Anthony</creatorcontrib><creatorcontrib>Devarakonda, Srikripa</creatorcontrib><creatorcontrib>Conroe, Heather M</creatorcontrib><creatorcontrib>Erdjument-Bromage, Hediye</creatorcontrib><title>PRDM16 controls a brown fat/skeletal muscle switch</title><title>Nature</title><addtitle>Nature</addtitle><description>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.</description><subject>adipocytes</subject><subject>Adipocytes, Brown - cytology</subject><subject>Adipocytes, Brown - metabolism</subject><subject>Adipocytes, White - metabolism</subject><subject>Adipose Tissue, Brown - cytology</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Brown adipose tissue</subject><subject>cell differentiation</subject><subject>Cell Differentiation - genetics</subject><subject>Cell Line</subject><subject>Cells</subject><subject>Cercopithecus aethiops</subject><subject>Chemicals</subject><subject>COS Cells</subject><subject>DNA-Binding Proteins - genetics</subject><subject>DNA-Binding Proteins - metabolism</subject><subject>Fundamental and applied biological sciences. 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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.</abstract><cop>London</cop><pub>Nature Publishing Group</pub><pmid>18719582</pmid><doi>10.1038/nature07182</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0028-0836 |
| ispartof | Nature, 2008-08, Vol.454 (7207), p.961-967 |
| issn | 0028-0836 1476-4687 1476-4679 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_2583329 |
| source | Springer Nature - Connect here FIRST to enable access |
| 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 |
| title | PRDM16 controls a brown fat/skeletal muscle switch |
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