UNLABELLED: Differences in expression of mRNA of genes regulating lipid and drug metabolism between hereditary hypertriglyceridemic rats (HHTg, accepted model of metabolic syndrome) and healthy Wistar-Kyoto (WKY) rats were studied. Also, differences in expression due to intake of high cholesterol diet (1% w/w) were determined to investigate possible differences in response of the WKY and HHTg rats to increased intake of dietary cholesterol. Levels of ATP-binding cassette transporters (ABCG5, ABCG8), fatty acid synthase (FAS) and cytochrome P450 (CYP2C11) mRNA were significantly lower in HHTg rats on standard laboratory diet; in contrary, CYP7A1, CYP2C6 and CYP2B2 gene expression was significantly higher. The WKY rats responded to high cholesterol diet by an increase in expression of mRNAs for sterol regulatory element binding protein (SREBP1c), CYP2B2 and CYP7A1; lower expression was found in the FAS, ABCG5, ABCG8, CYP4A1, CYP4A2 and acyl-CoA oxidase. HHTg rats responded to cholesterol intake in a similar manner, however, differences were found in expression of the FAS and CYP4A1 mRNA (decrease was not observed), CYP2B2 (decrease instead of an increase). CONCLUSIONS: (i) dietary cholesterol significantly influences expression of genes involved in lipid homeostasis and drug metabolism, and (ii) the HHTg rats responded to dietary cholesterol in a different way.

Faculty of Medicine Institute of Pharmacology Palacky University 775 15 Olomouc Czech Republic

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Differences in mRNA Expression of Selected Cytochrome P450, Transporters and Nuclear Receptors Among Various Rat Models of Metabolic Syndrome