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

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.