Molecular and Cellular Biochemistry

, Volume 335, Issue 1–2, pp 119–125

Increased liver oxidative stress and altered PUFA metabolism precede development of non-alcoholic steatohepatitis in SREBP-1a transgenic spontaneously hypertensive rats with genetic predisposition to hepatic steatosis

  • Hana Malínská
  • Olena Oliyarnyk
  • Miriam Hubová
  • Václav Zídek
  • Vladimír Landa
  • Miroslava Šimáková
  • Petr Mlejnek
  • Ludmila Kazdová
  • Theodore W. Kurtz
  • Michal Pravenec
Article

Abstract

The temporal relationship of hepatic steatosis and changes in liver oxidative stress and fatty acid (FA) composition to the development of non-alcoholic steatohepatitis (NASH) remain to be clearly defined. Recently, we developed an experimental model of hepatic steatosis and NASH, the transgenic spontaneously hypertensive rat (SHR) that overexpresses a dominant positive form of the human SREBP-1a isoform in the liver. These rats are genetically predisposed to hepatic steatosis at a young age that ultimately progresses to NASH in older animals. Young transgenic SHR versus SHR controls exhibited simple hepatic steatosis which was associated with significantly increased hepatic levels of oxidative stress markers, conjugated dienes, and TBARS, with decreased levels of antioxidative enzymes and glutathione and lower concentrations of plasma α- and γ-tocopherol. Transgenic rats exhibited increased plasma levels of saturated FA, decreased levels of n−3 and n−6 polyunsaturated FA (PUFA), and increased n−6/n−3 PUFA ratios. These results are consistent with the hypothesis that excess fat accumulation in the liver in association with increased oxidative stress and disturbances in the metabolism of saturated and unsaturated fatty acids may precede and contribute to the primary pathogenesis of NASH.

Keywords

Hepatic steatosis Non-alcoholic steatohepatitis Oxidative stress Fatty acid composition SREBP-1a transgenic spontaneously hypertensive rat 

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Copyright information

© Springer Science+Business Media, LLC. 2009

Authors and Affiliations

  • Hana Malínská
    • 1
  • Olena Oliyarnyk
    • 1
  • Miriam Hubová
    • 1
  • Václav Zídek
    • 2
  • Vladimír Landa
    • 2
  • Miroslava Šimáková
    • 2
  • Petr Mlejnek
    • 2
  • Ludmila Kazdová
    • 1
  • Theodore W. Kurtz
    • 3
  • Michal Pravenec
    • 2
  1. 1.Institute for Clinical and Experimental MedicinePragueCzech Republic
  2. 2.Institute of PhysiologyCzech Academy of SciencesPrague 4Czech Republic
  3. 3.University of CaliforniaSan FranciscoUSA

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