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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
4
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pubmed:dateCreated |
2011-4-4
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pubmed:abstractText |
SIRT1 regulates energy homeostasis by controlling the acetylation status and activity of a number of enzymes and transcriptional regulators. The fact that NAD(+) levels control SIRT1 activity confers a hypothetical basis for the design of new strategies to activate SIRT1 by increasing NAD(+) availability. Here we show that the deletion of the poly(ADP-ribose) polymerase-1 (PARP-1) gene, encoding a major NAD(+)-consuming enzyme, increases NAD(+) content and SIRT1 activity in brown adipose tissue and muscle. PARP-1(-/-) mice phenocopied many aspects of SIRT1 activation, such as a higher mitochondrial content, increased energy expenditure, and protection against metabolic disease. Also, the pharmacologic inhibition of PARP in vitro and in vivo increased NAD(+) content and SIRT1 activity and enhanced oxidative metabolism. These data show how PARP-1 inhibition has strong metabolic implications through the modulation of SIRT1 activity, a property that could be useful in the management not only of metabolic diseases, but also of cancer.
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pubmed:grant |
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pubmed:commentsCorrections |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
1932-7420
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pubmed:author |
pubmed-author:AuwerxJohanJ,
pubmed-author:BaiPéterP,
pubmed-author:BrunyánszkiAttilaA,
pubmed-author:CantóCarlesC,
pubmed-author:CenYanaY,
pubmed-author:HoutkooperRiekelt HRH,
pubmed-author:HuberAlineA,
pubmed-author:KissBorbálaB,
pubmed-author:Menissier-de MurciaJosianeJ,
pubmed-author:OudartHuguesH,
pubmed-author:SauveAnthony AAA,
pubmed-author:SchoonjansKristinaK,
pubmed-author:SchreiberValérieV,
pubmed-author:ThomasCharlesC,
pubmed-author:YamamotoHiroyasuH
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pubmed:copyrightInfo |
Copyright © 2011 Elsevier Inc. All rights reserved.
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pubmed:issnType |
Electronic
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pubmed:day |
6
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pubmed:volume |
13
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
461-8
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pubmed:dateRevised |
2011-9-26
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pubmed:meshHeading |
pubmed-meshheading:21459330-Adipose Tissue, Brown,
pubmed-meshheading:21459330-Animals,
pubmed-meshheading:21459330-Energy Metabolism,
pubmed-meshheading:21459330-Mice,
pubmed-meshheading:21459330-Mice, Knockout,
pubmed-meshheading:21459330-Mitochondria,
pubmed-meshheading:21459330-Muscle, Skeletal,
pubmed-meshheading:21459330-NAD,
pubmed-meshheading:21459330-Oxidative Stress,
pubmed-meshheading:21459330-Phenotype,
pubmed-meshheading:21459330-Poly(ADP-ribose) Polymerases,
pubmed-meshheading:21459330-RNA, Small Interfering,
pubmed-meshheading:21459330-RNA Interference,
pubmed-meshheading:21459330-Sirtuin 1
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pubmed:year |
2011
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pubmed:articleTitle |
PARP-1 inhibition increases mitochondrial metabolism through SIRT1 activation.
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pubmed:affiliation |
Biotechnologie et Signalisation Cellulaire, UMR7242 CNRS, Université de Strasbourg, ESBS, Illkirch, France.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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