Journal of Hepatology
Volume 48, Issue 1 , Pages 12-19, January 2008

Expression of hepatitis B virus proteins in transgenic mice alters lipid metabolism and induces oxidative stress in the liver

  • Fu Yang

      Affiliations

    • Department of Medical Genetics, Second Military Medical University, 800 Xiang-Yin Road, Shanghai 200433, PR China
    • These authors contributed equally to the manuscript.
  • ,
  • Shikai Yan

      Affiliations

    • School of Pharmacy, Second Military Medical University, Shanghai, PR China
    • These authors contributed equally to the manuscript.
  • ,
  • Ying He

      Affiliations

    • Department of Medical Genetics, Second Military Medical University, 800 Xiang-Yin Road, Shanghai 200433, PR China
  • ,
  • Fang Wang

      Affiliations

    • Department of Medical Genetics, Second Military Medical University, 800 Xiang-Yin Road, Shanghai 200433, PR China
  • ,
  • Shuxia Song

      Affiliations

    • Department of Medical Genetics, Second Military Medical University, 800 Xiang-Yin Road, Shanghai 200433, PR China
  • ,
  • Yingjun Guo

      Affiliations

    • Department of Medical Genetics, Second Military Medical University, 800 Xiang-Yin Road, Shanghai 200433, PR China
  • ,
  • Qi Zhou

      Affiliations

    • Department of Medical Genetics, Second Military Medical University, 800 Xiang-Yin Road, Shanghai 200433, PR China
  • ,
  • Yue Wang

      Affiliations

    • Department of Medical Genetics, Second Military Medical University, 800 Xiang-Yin Road, Shanghai 200433, PR China
  • ,
  • Zhongying Lin

      Affiliations

    • School of Pharmacy, Shanghai Jiaotong University, Shanghai, PR China
  • ,
  • Yun Yang

      Affiliations

    • School of Pharmacy, Second Military Medical University, Shanghai, PR China
  • ,
  • Weidong Zhang

      Affiliations

    • School of Pharmacy, Shanghai Jiaotong University, Shanghai, PR China
    • School of Pharmacy, Second Military Medical University, Shanghai, PR China
  • ,
  • Shuhan Sun

      Affiliations

    • Department of Medical Genetics, Second Military Medical University, 800 Xiang-Yin Road, Shanghai 200433, PR China
    • Corresponding Author InformationCorresponding author. Tel./fax: +86 21 25070331.

Received 13 March 2007; received in revised form 11 June 2007; accepted 18 June 2007. published online 10 September 2007.

Associate Editor: K. Koike

Background/Aims

Hepatitis B virus transgenic mice (HBV-Tg mice) have been widely used as animal models in the study of pathogenesis and control of hepatitis B. It is important for the evaluation of such animal models to define the physiological differences between HBV-Tg and wild-type mice. The aim of this research was to investigate whether the integrated system biology approach that combines proteomics and metabonomics describes the physiological changes and provides new insights into the pathogenesis of the early stages of HBV infection.

Methods

In this study the protein and metabolite profiles of the liver were established based on two-dimensional electrophoresis and HPLC/MS analysis.

Results

Several protein molecules, whose expression was altered in HBV-Tg mouse liver, were identified including protective enzymes against oxidative stress and regulatory proteins related to lipid metabolism. Metabonomics confirmed the potential derangement of lipid metabolism by discovering the intermediate and the final products of lipid metabolism that were markedly changed in transgenic mice.

Conclusions

This study demonstrated that HBV antigens could impair host cell lipid metabolism and induce modest oxidative stress in vivo.

Keywords: Hepatitis B virus, Lipid metabolism, Metabonomics, Proteomics, Oxidative stress

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 The authors declare that they have no conflict of interest to disclose concerning this manuscript.

PII: S0168-8278(07)00469-2

doi:10.1016/j.jhep.2007.06.021

Journal of Hepatology
Volume 48, Issue 1 , Pages 12-19, January 2008