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Gut. 2014 Jan;63(1):170-8. doi: 10.1136/gutjnl-2012-303150. Epub 2013 Jan 24.

Yin Yang 1 promotes hepatic steatosis through repression of farnesoid X receptor in obese mice.

Author information

  • 1Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrinology and Metabolism, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, , Shanghai, China.

Abstract

BACKGROUND:

Non-alcoholic fatty liver disease (NAFLD) is characterised by accumulation of excessive triglycerides in the liver. Obesity is usually associated with NAFLD through an unknown mechanism.

OBJECTIVE:

To investigate the roles of Yin Yang 1 (YY1) in the progression of obesity-associated hepatosteatosis.

METHODS:

Expression levels of hepatic YY1 were identified by microarray analysis in high-fat-diet (HFD)-induced obese mice. Liver triglyceride metabolism was analysed in mice with YY1 overexpression and suppression.

RESULTS:

YY1 expression was markedly upregulated in HFD-induced obese mice and NAFLD patients. Overexpression of YY1 in healthy mice promoted hepatosteatosis under high-fat dietary conditions, whereas liver-specific ablation of YY1 using adenoviral shRNA ameliorated triglyceride accumulation in obese mice. At the molecular level, YY1 suppressed farnesoid X receptor (FXR) expression through binding to the YY1 responsive element at intron 1 of the FXR gene.

CONCLUSIONS:

These findings indicate that YY1 plays a crucial role in obesity-associated hepatosteatosis, through repression of FXR expression.

KEYWORDS:

Nonalcoholic Steatohepatitis; Signal Transduction

PMID:
23348961
[PubMed - indexed for MEDLINE]
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