| Transcription coactivator mediator subunit MED1 is required for the development of fatty liver in the mouse. | |
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MedLine Citation:
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PMID: 21480322 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Peroxisome proliferator-activated receptor-γ (PPARγ), 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 PPARγ-stimulated adipogenic hepatic steatosis. Mediator forms the bridge between transcriptional activators and RNA polymerase II. MED1 interacts with nuclear receptors such as PPARγ and other transcriptional activators. Liver-specific MED1 knockout (MED1(ΔLiv) ) mice, when fed a high-fat (60% kcal fat) diet for up to 4 months failed to develop fatty liver. Similarly, MED1(ΔLiv) mice injected with adenovirus-PPARγ (Ad/PPARγ) 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/PPARγ developed severe hepatic steatosis. Gene expression profiling and northern blot analyses of Ad/PPARγ-injected mouse livers showed impaired induction in MED1(ΔLiv) 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/PPARγ. Re-expression of MED1 using adenovirally-driven MED1 (Ad/MED1) in MED1(ΔLiv) mouse liver restored PPARγ-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 PPARγ overexpression. Conclusion: We conclude that transcription coactivator MED1 is required for high-fat diet-induced and PPARγ-stimulated fatty liver development, which suggests that MED1 may be considered a potential therapeutic target for hepatic steatosis. (HEPATOLOGY 2011;). |
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Authors:
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Liang Bai; Yuzhi Jia; Navin Viswakarma; Jiansheng Huang; Aurore Vluggens; Nathan E Wolins; Nadereh Jafari; M Sambasiva Rao; Jayme Borensztajn; Gongshe Yang; Janardan K Reddy |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Hepatology (Baltimore, Md.) Volume: 53 ISSN: 1527-3350 ISO Abbreviation: Hepatology Publication Date: 2011 Apr |
Date Detail:
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Created Date: 2011-04-11 Completed Date: 2011-06-14 Revised Date: 2012-04-04 |
Medline Journal Info:
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Nlm Unique ID: 8302946 Medline TA: Hepatology Country: United States |
Other Details:
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Languages: eng Pagination: 1164-74 Citation Subset: IM |
Copyright Information:
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Copyright © 2011 American Association for the Study of Liver Diseases. |
Affiliation:
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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. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Dietary Fats / administration & dosage Fatty Liver / etiology* Gene Expression Profiling Genes, Regulator Mediator Complex Subunit 1 / deficiency, physiology* Mice PPAR gamma / biosynthesis, pharmacology |
| Grant Support | |
ID/Acronym/Agency:
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DK083163/DK/NIDDK NIH HHS; DK56351/DK/NIDDK NIH HHS; GM23750/GM/NIGMS NIH HHS; R01 DK083163-08/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Dietary Fats; 0/Mediator Complex Subunit 1; 0/PPAR gamma |
| Comments/Corrections | |
Erratum In:
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Hepatology. 2011 Sep 2;54(3):1114 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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