Source:http://linkedlifedata.com/resource/pubmed/id/21480322
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
4
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| pubmed:dateCreated |
2011-4-11
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| pubmed:abstractText |
Peroxisome proliferator-activated receptor-? (PPAR?), a nuclear receptor, when overexpressed in liver stimulates the induction of adipocyte-specific and lipogenesis-related genes and causes hepatic steatosis. We report here that Mediator 1 (MED1; also known as PBP or TRAP220), a key subunit of the Mediator complex, is required for high-fat diet-induced hepatic steatosis as well as PPAR?-stimulated adipogenic hepatic steatosis. Mediator forms the bridge between transcriptional activators and RNA polymerase II. MED1 interacts with nuclear receptors such as PPAR? and other transcriptional activators. Liver-specific MED1 knockout (MED1(?Liv) ) mice, when fed a high-fat (60% kcal fat) diet for up to 4 months failed to develop fatty liver. Similarly, MED1(?Liv) mice injected with adenovirus-PPAR? (Ad/PPAR?) by tail vein also did not develop fatty liver, whereas mice with MED1 (MED1(fl/fl) ) fed a high-fat diet or injected with Ad/PPAR? developed severe hepatic steatosis. Gene expression profiling and northern blot analyses of Ad/PPAR?-injected mouse livers showed impaired induction in MED1(?Liv) mouse liver of adipogenic markers, such as aP2, adipsin, adiponectin, and lipid droplet-associated genes, including caveolin-1, CideA, S3-12, and others. These adipocyte-specific and lipogenesis-related genes are strongly induced in MED1(fl/fl) mouse liver in response to Ad/PPAR?. Re-expression of MED1 using adenovirally-driven MED1 (Ad/MED1) in MED1(?Liv) mouse liver restored PPAR?-stimulated hepatic adipogenic response. These studies also demonstrate that disruption of genes encoding other coactivators such as SRC-1, PRIC285, PRIP, and PIMT had no effect on hepatic adipogenesis induced by PPAR? overexpression. Conclusion: We conclude that transcription coactivator MED1 is required for high-fat diet-induced and PPAR?-stimulated fatty liver development, which suggests that MED1 may be considered a potential therapeutic target for hepatic steatosis. (HEPATOLOGY 2011;).
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| pubmed:grant | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical | |
| pubmed:status |
MEDLINE
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| pubmed:month |
Apr
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| pubmed:issn |
1527-3350
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| pubmed:author |
pubmed-author:BaiLiangL,
pubmed-author:BorensztajnJaymeJ,
pubmed-author:HuangJianshengJ,
pubmed-author:JafariNaderehN,
pubmed-author:JiaYuzhiY,
pubmed-author:RaoM SambasivaMS,
pubmed-author:ReddyJanardan KJK,
pubmed-author:ViswakarmaNavinN,
pubmed-author:VluggensAuroreA,
pubmed-author:WolinsNathan ENE,
pubmed-author:YangGongsheG
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| pubmed:copyrightInfo |
Copyright © 2011 American Association for the Study of Liver Diseases.
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| pubmed:issnType |
Electronic
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| pubmed:volume |
53
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| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
1164-74
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| pubmed:meshHeading |
pubmed-meshheading:21480322-Animals,
pubmed-meshheading:21480322-Dietary Fats,
pubmed-meshheading:21480322-Fatty Liver,
pubmed-meshheading:21480322-Gene Expression Profiling,
pubmed-meshheading:21480322-Genes, Regulator,
pubmed-meshheading:21480322-Mediator Complex Subunit 1,
pubmed-meshheading:21480322-Mice,
pubmed-meshheading:21480322-PPAR gamma
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| pubmed:year |
2011
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| pubmed:articleTitle |
Transcription coactivator mediator subunit MED1 is required for the development of fatty liver in the mouse.
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| pubmed:affiliation |
Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, IL; Laboratory of Animal Fat Deposition and Muscle Development, College of Animal Science and Technology, Northwest A&F University, Shaanxi, China.
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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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