Authors: JIA, YUZHI; VISWAKARMA, NAVIN; FU, TAO; YU, SONGTAO; RAO, M. SAMBASIVA; BORENSZTAJN, JAYME; REDDY, JANARDAN K.

Source: Gene Expression, Volume 14, Number 5, 2009 , pp. 291-306(16)

Publisher: Cognizant Communication Corporation

Abstract:

Glucocorticoid receptor (GR) agonist dexamethasone (Dex) induces hepatic steatosis and enhances constitutive androstane receptor (CAR) expression in the liver. CAR is known to worsen hepatic injury in nonalcoholic hepatic steatosis. Because transcription coactivator MED1/PPARBP gene is required for GR- and CAR-mediated transcriptional activation, we hypothesized that disruption of MED1/PPARBP gene in liver cells would result in the attenuation of Dex-induced hepatic steatosis. Here we show that liver-specific disruption of MED1 gene (MED1^Liv) improves Dex-induced steatotic phenotype in the liver. In wild-type mice Dex induced severe hepatic steatosis and caused reduction in medium- and short-chain acyl-CoA dehydrogenases that are responsible for mitochondrial -oxidation. In contrast, Dex did not induce hepatic steatosis in mice conditionally null for hepatic MED1, as it failed to inhibit fatty acid oxidation enzymes in the liver. MED1^Liv livers had lower levels of GR-regulated CAR mRNA compared to wild-type mouse livers. Microarray gene expression profiling showed that absence of MED1 affects the expression of the GR-regulated genes responsible for energy metabolism in the liver. These results establish that absence of MED1 in the liver diminishes Dex-induced hepatic steatosis by altering the GR- and CAR-dependent gene functions.

References: 32 references open in new window

Articles that cite this article?

Keywords: Mediator complex subunit 1 (MED1); PPARBP; Hepatic steatosis; Dexamethasone; Glucocorticoid receptor; Constitutive androstane receptor

Document Type: Research article

DOI: http://dx.doi.org/10.3727/105221609788681213

Publication date: 2009-05-01

More about this publication?

• The Molecular and Cellular Biology area of Gene Expression covers all aspects of the gene including it structure, functions, and regulation in prokaryotes, eukaryotes, and viruses; molecular and cell biological aspects of cell growth and development, chromatin structure and function. These include topics such as DNA replication, DNA repair, gene transcription, transcriptional control, RNA processing, posttranscriptional control, oncogenes, molecular mechanisms of action of hormones, molecular mechanism of cellular differentiation, growth and development, protein synthesis, and posttranslational control.
  The Molecular and Cellular Neuroscience area of Gene Expression covers all aspects of gene expression as described but is devoted exclusively to the nervous system in health and disease. Topics include studies of neurogenesis, development, aging, and neurodegeneration. Complex neural systems, motor control, special senses, and higher cortical function, when viewed from the perspective of gene expression, are appropriate for the journal. Research related to molecular mechanisms of drug tolerance, dependence, and withdrawal are solicited. Manuscripts on state-of-the-art methods and protocols for molecular profiling of neuronal structure and function are welcome.

Related content

• In this: publication
• By this: publisher
• In this Subject: Biotechnology ,  Genetics
• By this author: JIA, YUZHI ;  VISWAKARMA, NAVIN ;  FU, TAO ;  YU, SONGTAO ;  RAO, M. SAMBASIVA ;  BORENSZTAJN, JAYME ;  REDDY, JANARDAN K.

Website © Publishing Technology. Article copyright remains with the publisher, society or author(s) as specified within the article.

• Terms and conditions
• Privacy policy
• Information for advertisers