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.
Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrinology and Metabolism, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, , Shanghai, China.
Yan
Y
Lu
Zhimin
Z
Ma
Zhijian
Z
Zhang
Xuelian
X
Xiong
Xiaolin
X
Wang
Huijie
H
Zhang
Guojun
G
Shi
Xuefeng
X
Xia
Guang
G
Ning
Xiaoying
X
Li
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D047369:Chromatin Immunoprecipitation; D005234:Fatty Liver / Q000209:etiology* / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D065626:Non-alcoholic Fatty Liver Disease; D009765:Obesity / Q000150:complications / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D060888:Real-Time Polymerase Chain Reaction; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D014280:Triglycerides / Q000378:metabolism; D015854:Up-Regulation; D050986:YY1 Transcription Factor / Q000378:metabolism*; D000099150:Receptor, Farnesoid X-Activated
D015415:Biomarkers; D018160:Receptors, Cytoplasmic and Nuclear; D014280:Triglycerides; D050986:YY1 Transcription Factor; D000099150:Receptor, Farnesoid X-Activated; C494698:YY1 protein, human; C494699:Yy1 protein, mouse
Nonalcoholic Steatohepatitis; Signal Transduction