Complementary action of the PGC-1 coactivators in mitochondrial biogenesis and brown fat differentiation
Mitochondria play an essential role in the ability of brown fat to generate heat, and the PGC-1 coactivators control several aspects of mitochondrial biogenesis. To investigate their specific roles in brown fat cells, we generated immortal preadipocyte lines from the brown adipose tissue of mice lac...
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| Veröffentlicht in: | Cell metabolism 2006-05, Vol.3 (5), p.333-341 |
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| creator | Uldry, Marc Yang, Wenli St-Pierre, Julie Lin, Jiandie Seale, Patrick Spiegelman, Bruce M. |
| description | Mitochondria play an essential role in the ability of brown fat to generate heat, and the PGC-1 coactivators control several aspects of mitochondrial biogenesis. To investigate their specific roles in brown fat cells, we generated immortal preadipocyte lines from the brown adipose tissue of mice lacking PGC-1α. We could then efficiently knockdown PGC-1β expression by shRNA expression. Loss of PGC-1α did not alter brown fat differentiation but severely reduced the induction of thermogenic genes. Cells deficient in either PGC-1α or PGC-1β coactivators showed a small decrease in the differentiation-dependant program of mitochondrial biogenesis and respiration; however, this increase in mitochondrial number and function was totally abolished during brown fat differentiation when both PGC-1α and PGC-1β were deficient. These data show that PGC-1α is essential for brown fat thermogenesis but not brown fat differentiation, and the PGC-1 coactivators play an absolutely essential but complementary function in differentiation-induced mitochondrial biogenesis. |
| doi_str_mv | 10.1016/j.cmet.2006.04.002 |
| format | Article |
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Yang, Wenli ; St-Pierre, Julie ; Lin, Jiandie ; Seale, Patrick ; Spiegelman, Bruce M.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c464t-ea5562e1a2e92d7a5125e7c687fc1bc1930d24705612b76e22745dae8d2fb9af3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Adipocytes - cytology</topic><topic>Adipocytes - drug effects</topic><topic>Adipocytes - metabolism</topic><topic>Adipose Tissue, Brown - cytology</topic><topic>Adipose Tissue, Brown - drug effects</topic><topic>Adipose Tissue, Brown - metabolism</topic><topic>Animals</topic><topic>CCAAT-Enhancer-Binding Protein-beta - genetics</topic><topic>CCAAT-Enhancer-Binding Protein-beta - metabolism</topic><topic>Cell Differentiation</topic><topic>Cell Line</topic><topic>Cell Respiration</topic><topic>Cyclic CMP - analogs & derivatives</topic><topic>Cyclic CMP - pharmacology</topic><topic>Cytochromes c - genetics</topic><topic>Cytochromes c - metabolism</topic><topic>Gene Expression Profiling</topic><topic>Gene Expression Regulation</topic><topic>HUMDISEASE</topic><topic>Ion Channels - genetics</topic><topic>Ion Channels - metabolism</topic><topic>Mice</topic><topic>Mice, Knockout</topic><topic>Mitochondria - drug effects</topic><topic>Mitochondria - genetics</topic><topic>Mitochondria - metabolism</topic><topic>Mitochondrial Proteins - genetics</topic><topic>Mitochondrial Proteins - metabolism</topic><topic>Oligonucleotide Array Sequence Analysis</topic><topic>Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha</topic><topic>RNA Interference</topic><topic>RNA, Messenger - metabolism</topic><topic>Thermogenesis - genetics</topic><topic>Trans-Activators - genetics</topic><topic>Trans-Activators - metabolism</topic><topic>Transcription Factors - genetics</topic><topic>Transcription Factors - metabolism</topic><topic>Uncoupling Protein 1</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Uldry, Marc</creatorcontrib><creatorcontrib>Yang, Wenli</creatorcontrib><creatorcontrib>St-Pierre, Julie</creatorcontrib><creatorcontrib>Lin, Jiandie</creatorcontrib><creatorcontrib>Seale, Patrick</creatorcontrib><creatorcontrib>Spiegelman, Bruce M.</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Cell metabolism</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Uldry, Marc</au><au>Yang, Wenli</au><au>St-Pierre, Julie</au><au>Lin, Jiandie</au><au>Seale, Patrick</au><au>Spiegelman, Bruce M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Complementary action of the PGC-1 coactivators in mitochondrial biogenesis and brown fat differentiation</atitle><jtitle>Cell metabolism</jtitle><addtitle>Cell Metab</addtitle><date>2006-05-01</date><risdate>2006</risdate><volume>3</volume><issue>5</issue><spage>333</spage><epage>341</epage><pages>333-341</pages><issn>1550-4131</issn><eissn>1932-7420</eissn><abstract>Mitochondria play an essential role in the ability of brown fat to generate heat, and the PGC-1 coactivators control several aspects of mitochondrial biogenesis. To investigate their specific roles in brown fat cells, we generated immortal preadipocyte lines from the brown adipose tissue of mice lacking PGC-1α. We could then efficiently knockdown PGC-1β expression by shRNA expression. Loss of PGC-1α did not alter brown fat differentiation but severely reduced the induction of thermogenic genes. Cells deficient in either PGC-1α or PGC-1β coactivators showed a small decrease in the differentiation-dependant program of mitochondrial biogenesis and respiration; however, this increase in mitochondrial number and function was totally abolished during brown fat differentiation when both PGC-1α and PGC-1β were deficient. 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| subjects | Adipocytes - cytology Adipocytes - drug effects Adipocytes - metabolism Adipose Tissue, Brown - cytology Adipose Tissue, Brown - drug effects Adipose Tissue, Brown - metabolism Animals CCAAT-Enhancer-Binding Protein-beta - genetics CCAAT-Enhancer-Binding Protein-beta - metabolism Cell Differentiation Cell Line Cell Respiration Cyclic CMP - analogs & derivatives Cyclic CMP - pharmacology Cytochromes c - genetics Cytochromes c - metabolism Gene Expression Profiling Gene Expression Regulation HUMDISEASE Ion Channels - genetics Ion Channels - metabolism Mice Mice, Knockout Mitochondria - drug effects Mitochondria - genetics Mitochondria - metabolism Mitochondrial Proteins - genetics Mitochondrial Proteins - metabolism Oligonucleotide Array Sequence Analysis Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha RNA Interference RNA, Messenger - metabolism Thermogenesis - genetics Trans-Activators - genetics Trans-Activators - metabolism Transcription Factors - genetics Transcription Factors - metabolism Uncoupling Protein 1 |
| title | Complementary action of the PGC-1 coactivators in mitochondrial biogenesis and brown fat differentiation |
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