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.
['Lu|Yan|Y|', 'Ma|Zhimin|Z|', 'Zhang|Zhijian|Z|', 'Xiong|Xuelian|X|', 'Wang|Xiaolin|X|', 'Zhang|Huijie|H|', 'Shi|Guojun|G|', 'Xia|Xuefeng|X|', 'Ning|Guang|G|', 'Li|Xiaoying|X|']
D000818:Animals D015415:Biomarkers D015153:Blotting, Western D047369:Chromatin Immunoprecipitation D005234:Fatty Liver D006801:Humans D008099:Liver D008297:Male D051379:Mice D008810:Mice, Inbred C57BL D008822:Mice, Transgenic D065626:Non-alcoholic Fatty Liver Disease D009765:Obesity D020411:Oligonucleotide Array Sequence Analysis D060888:Real-Time Polymerase Chain Reaction D018160:Receptors, Cytoplasmic and Nuclear D014280:Triglycerides D015854:Up-Regulation D050986:YY1 Transcription Factor
Nonalcoholic Steatohepatitis Signal Transduction