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| Subject Categories: Cellular Metabolism |
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| The EMBO Journal
(2007) 26, 1913–1923, doi:10.1038/sj.emboj.7601633 Published online 8 March 2007 |
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Metabolic control of muscle mitochondrial function and fatty acid oxidation through SIRT1/PGC-1 |
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| Zachary Gerhart-Hines1, 2, Joseph T Rodgers1, 2, Olivia Bare3, Carles Lerin1, 2, Seung-Hee Kim1, 2, Raul Mostoslavsky4, Frederick W Alt4, Zhidan Wu3 and Pere Puigserver1, 2 |
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1 Dana-Farber Cancer Institute and Department of Cell Biology, Harvard Medical School, Boston, MA, USA 2 Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, MD, USA 3 Novartis Institutes for Biomedical Research Inc., Cambridge, MA, USA 4 Howard ughes Medical Institute, Department of Genetics, The Children's Hospital, CBR Institute for Biomedical Research, Harvard Medical School, Boston, MA, USA To whom correspondence should be addressed Pere Puigserver, Dana-Farber Cancer Institute, Department of Cell Biology, Harvard Medical School, One Jimmy Fund Way/ Smith-936C, Boston, MA 02115, USA. Tel.: +1 617 582 7977; Fax: +1 617 632 4770; E-mail: pere_puigserver@dfci.harvard.edu Received 13 September 2006; Accepted 5 February 2007; Published online 8 March 2007. |
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| Abstract |
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| In mammals, maintenance of energy and nutrient homeostasis during food deprivation is accomplished through an increase in mitochondrial fatty acid oxidation in peripheral tissues. An important component that drives this cellular oxidative process is the transcriptional coactivator PGC-1. Here, we show that fasting induced PGC-1 deacetylation in skeletal muscle and that SIRT1 deacetylation of PGC-1 is required for activation of mitochondrial fatty acid oxidation genes. Moreover, expression of the acetyltransferase, GCN5, or the SIRT1 inhibitor, nicotinamide, induces PGC-1 acetylation and decreases expression of PGC-1 target genes in myotubes. Consistent with a switch from glucose to fatty acid oxidation that occurs in nutrient deprivation states, SIRT1 is required for induction and maintenance of fatty acid oxidation in response to low glucose concentrations. Thus, we have identified SIRT1 as a functional regulator of PGC-1 that induces a metabolic gene transcription program of mitochondrial fatty acid oxidation. These results have implications for understanding selective nutrient adaptation and how it might impact lifespan or metabolic diseases such as obesity and diabetes. |
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| Keywords: caloric restriction, gene transcription, lipid metabolism, mitochondrial oxidation, Sirtuins |
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Top of page MORE ARTICLES LIKE THISThese links to content published by NPG are automatically generated NEWS AND VIEWSHitting transcription in all the right places Nature Structural & Molecular Biology News and Views (01 May 2005) Nature Medicine News and Views (01 Nov 2003) RESEARCHMetabolic control of muscle mitochondrial function and fatty acid oxidation through SIRT1/PGC-1α The EMBO Journal Article The EMBO Journal Article (11 Jul 2007) |
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