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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
50
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pubmed:dateCreated |
2000-1-13
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pubmed:abstractText |
Dietary polyunsaturated fatty acids (PUFA) are negative regulators of hepatic lipogenesis that exert their effects primarily at the level of transcription. Sterol regulatory element-binding proteins (SREBPs) are transcription factors responsible for the regulation of cholesterol, fatty acid, and triglyceride synthesis. In particular, SREBP-1 is known to play a crucial role in the regulation of lipogenic gene expression in the liver. To explore the possible involvement of SREBP-1 in the suppression of hepatic lipogenesis by PUFA, we challenged wild-type mice and transgenic mice overexpressing a mature form of SREBP-1 in the liver with dietary PUFA. In the liver of wild-type mice, dietary PUFA drastically decreased the mature, cleaved form of SREBP-1 protein in the nucleus, whereas the precursor, uncleaved form in the membranes was not suppressed. The decreases in mature SREBP-1 paralleled those in mRNAs for lipogenic enzymes such as fatty acid synthase and acetyl-CoA carboxylase. In the transgenic mice, dietary PUFA did not reduce the amount of transgenic SREBP-1 protein, excluding the possibility that PUFA accelerated the degradation of mature SREBP-1. The resulting sustained expression of mature SREBP-1 almost completely canceled the suppression of lipogenic gene expression by PUFA in the SREBP-1 transgenic mice. These results demonstrate that the suppressive effect of PUFA on lipogenic enzyme genes in the liver is caused by a decrease in the mature form of SREBP-1 protein, which is presumably due to the reduced cleavage of SREBP-1 precursor protein.
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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 |
http://linkedlifedata.com/resource/pubmed/chemical/CCAAT-Enhancer-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Chromans,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Dietary Carbohydrates,
http://linkedlifedata.com/resource/pubmed/chemical/Dietary Fats, Unsaturated,
http://linkedlifedata.com/resource/pubmed/chemical/Dietary Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Fenofibrate,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/SREBF1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Srebf1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Srebf1 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Stearoyl-CoA Desaturase,
http://linkedlifedata.com/resource/pubmed/chemical/Sterol Regulatory Element Binding...,
http://linkedlifedata.com/resource/pubmed/chemical/Thiazoles,
http://linkedlifedata.com/resource/pubmed/chemical/Thiazolidinediones,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/troglitazone
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
0021-9258
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pubmed:author |
pubmed-author:Amemiya-KudoMM,
pubmed-author:GotodaTT,
pubmed-author:HaradaKK,
pubmed-author:HastyA HAH,
pubmed-author:IizukaYY,
pubmed-author:IshibashiSS,
pubmed-author:NagaiRR,
pubmed-author:OhashiKK,
pubmed-author:OkazakiHH,
pubmed-author:OsugaJJ,
pubmed-author:ShimanoHH,
pubmed-author:ShionoiriFF,
pubmed-author:TamuraYY,
pubmed-author:YahagiNN,
pubmed-author:YamadaNN
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pubmed:issnType |
Print
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pubmed:day |
10
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pubmed:volume |
274
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
35840-4
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:10585468-Animal Feed,
pubmed-meshheading:10585468-Animals,
pubmed-meshheading:10585468-CCAAT-Enhancer-Binding Proteins,
pubmed-meshheading:10585468-Cell Nucleus,
pubmed-meshheading:10585468-Chromans,
pubmed-meshheading:10585468-DNA-Binding Proteins,
pubmed-meshheading:10585468-Diet,
pubmed-meshheading:10585468-Dietary Carbohydrates,
pubmed-meshheading:10585468-Dietary Fats, Unsaturated,
pubmed-meshheading:10585468-Dietary Proteins,
pubmed-meshheading:10585468-Fenofibrate,
pubmed-meshheading:10585468-Gene Expression Regulation, Enzymologic,
pubmed-meshheading:10585468-Glycolysis,
pubmed-meshheading:10585468-Humans,
pubmed-meshheading:10585468-Liver,
pubmed-meshheading:10585468-Male,
pubmed-meshheading:10585468-Mice,
pubmed-meshheading:10585468-Mice, Inbred C57BL,
pubmed-meshheading:10585468-Mice, Transgenic,
pubmed-meshheading:10585468-Nuclear Proteins,
pubmed-meshheading:10585468-Rats,
pubmed-meshheading:10585468-Stearoyl-CoA Desaturase,
pubmed-meshheading:10585468-Sterol Regulatory Element Binding Protein 1,
pubmed-meshheading:10585468-Thiazoles,
pubmed-meshheading:10585468-Thiazolidinediones,
pubmed-meshheading:10585468-Transcription, Genetic,
pubmed-meshheading:10585468-Transcription Factors
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pubmed:year |
1999
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pubmed:articleTitle |
A crucial role of sterol regulatory element-binding protein-1 in the regulation of lipogenic gene expression by polyunsaturated fatty acids.
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pubmed:affiliation |
Department of Metabolic Diseases, Faculty 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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