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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
28
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pubmed:dateCreated |
2003-7-4
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pubmed:abstractText |
The tumor suppressor p53 is a transcription factor that activates or represses its target genes after various genotoxic stresses. We have previously shown that sterol regulatory element-binding protein-1 (SREBP-1), a key transcriptional regulator of triglyceride synthesis, and the lipogenic enzymes under its control are markedly suppressed in adipocytes from genetically obese ob/ob mice. Here we demonstrate that p53 and its target genes are highly induced in adipocytes of ob/ob mice in a fed state, leading to the negative regulation of SREBP-1 and thereby lipogenic genes. In fact, disruption of p53 in ob/ob mice completely suppressed the p53-regulated genes to wild-type levels and partially restored expression of lipogenic enzymes. Consistently, reporter gene analysis showed that p53 overexpression suppressed the promoter activity of the SREBP-1c gene and its downstream genes. Thus, the activation of p53 might constitute a negative feedback loop against excess fat accumulation in adipocytes. In conclusion, we discovered a novel role of p53 in the pathophysiology of obesity.
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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 |
Jul
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pubmed:issn |
0021-9258
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pubmed:author |
pubmed-author:GotodaTakanariT,
pubmed-author:IdeTomohiroT,
pubmed-author:IizukaYokoY,
pubmed-author:IshibashiShunS,
pubmed-author:KimuraSatoshiS,
pubmed-author:MatsuzakaTakashiT,
pubmed-author:NagaiRyozoR,
pubmed-author:NajimaYuhoY,
pubmed-author:NakagawaYoshimiY,
pubmed-author:OhashiKenK,
pubmed-author:OkazakiHiroakiH,
pubmed-author:OsugaJun-IchiJ,
pubmed-author:SekiyaMotohiroM,
pubmed-author:ShimanoHitoshiH,
pubmed-author:TamuraYoshiakiY,
pubmed-author:TomitaSachikoS,
pubmed-author:YahagiNaoyaN,
pubmed-author:YamadaNobuhiroN
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pubmed:issnType |
Print
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pubmed:day |
11
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pubmed:volume |
278
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
25395-400
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:12734185-Adipose Tissue,
pubmed-meshheading:12734185-Animals,
pubmed-meshheading:12734185-Blotting, Northern,
pubmed-meshheading:12734185-Blotting, Western,
pubmed-meshheading:12734185-CCAAT-Enhancer-Binding Proteins,
pubmed-meshheading:12734185-Cell Nucleus,
pubmed-meshheading:12734185-Crosses, Genetic,
pubmed-meshheading:12734185-DNA-Binding Proteins,
pubmed-meshheading:12734185-Down-Regulation,
pubmed-meshheading:12734185-Gene Expression Regulation,
pubmed-meshheading:12734185-Genotype,
pubmed-meshheading:12734185-Immunoblotting,
pubmed-meshheading:12734185-Luciferases,
pubmed-meshheading:12734185-Mice,
pubmed-meshheading:12734185-Mice, Inbred C57BL,
pubmed-meshheading:12734185-Mice, Obese,
pubmed-meshheading:12734185-Obesity,
pubmed-meshheading:12734185-Plasmids,
pubmed-meshheading:12734185-Promoter Regions, Genetic,
pubmed-meshheading:12734185-RNA, Messenger,
pubmed-meshheading:12734185-Sterol Regulatory Element Binding Protein 1,
pubmed-meshheading:12734185-Transcription, Genetic,
pubmed-meshheading:12734185-Transcription Factors,
pubmed-meshheading:12734185-Transfection,
pubmed-meshheading:12734185-Tumor Suppressor Protein p53,
pubmed-meshheading:12734185-Up-Regulation
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pubmed:year |
2003
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pubmed:articleTitle |
p53 Activation in adipocytes of obese mice.
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pubmed:affiliation |
Department of Internal Medicine, Graduate School of Medicine, University of Tokyo, Tokyo 113-8655, Japan.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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