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Yin Yang 1 promotes hepatic steatosis through repression of farnesoid X receptor in obese mice
  1. Yan Lu1,
  2. Zhimin Ma1,
  3. Zhijian Zhang1,
  4. Xuelian Xiong1,
  5. Xiaolin Wang1,
  6. Huijie Zhang1,
  7. Guojun Shi1,
  8. Xuefeng Xia2,
  9. Guang Ning1,3,
  10. Xiaoying Li1,3
  1. 1Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrinology and Metabolism, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
  2. 2Genomic Medicine and Center for Diabetes Research, The Methodist Hospital Research Institute, Weill Cornell Medical College, Houston, Texas, USA
  3. 3The Key Laboratory of Endocrine Tumors and the Division of Endocrine and Metabolic Diseases, E-Institute of Shanghai Universities, Shanghai, China
  1. Correspondence to Dr Xiaoying Li and Dr Guang Ning, Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrinology and Metabolism, 197 Ruijin 2nd Road, Shanghai 200025, China; lixy{at}sibs.ac.cn, guangning{at}medmail.com.cn

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.

  • Nonalcoholic Steatohepatitis
  • Signal Transduction

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