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 alpha- and gamma-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.
- MeSH
- genetická predispozice k nemoci MeSH
- játra metabolismus patologie MeSH
- krysa rodu rattus MeSH
- lidé MeSH
- nenasycené mastné kyseliny metabolismus MeSH
- oxidační stres MeSH
- potkani inbrední SHR MeSH
- potkani transgenní MeSH
- protein SREBP1 genetika metabolismus MeSH
- ztučnělá játra genetika metabolismus patologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
- MeSH
- exprese genu MeSH
- financování organizované MeSH
- fosfolipidy metabolismus MeSH
- mastné kyseliny biosyntéza imunologie metabolismus MeSH
- membránové lipidy analýza imunologie MeSH
- metabolismus lipidů imunologie MeSH
- oxidační stres imunologie MeSH
- potkani inbrední SHR imunologie metabolismus MeSH
- ztučnělá játra enzymologie chemicky indukované MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- MeSH
- financování organizované MeSH
- inzulinová rezistence MeSH
- metabolický syndrom metabolismus MeSH
- nikotinamidfosforibosyltransferasa biosyntéza fyziologie metabolismus MeSH
- potkani Wistar metabolismus MeSH
- proteiny vázající retinol MeSH
- resistin MeSH
- serpiny MeSH
- tuková tkáň chemie metabolismus MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- abstrakt z konference MeSH
