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.