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Diet induced regulation of genes involved in cholesterol metabolism in rat liver parenchymal and Kupffer cells.

Hoekstra M., Out R., Kruijt J.K., Van Eck M., Van Berkel T.J.

BACKGROUND/AIMS: Feeding rodents atherogenic diets enriched in cholesterol or cholic acid changes hepatic cholesterol metabolism. In the present study, the effect of an atherogenic diet enriched in cholesterol and cholic acid on cellular hepatic cholesterol metabolism was studied. METHODS: Gene and protein expression analysis was performed on parenchymal, endothelial, and Kupffer cells isolated from rats fed a chow or atherogenic diet using quantitative real-time PCR and immunoblotting, respectively. RESULTS: The atherogenic diet raised the serum cholesterol concentration 11-fold, mostly in the VLDL fraction, and led to heavy lipid loading of rat liver parenchymal and Kupffer cells. Only moderate changes in the expression of genes involved in cholesterol metabolism were observed in parenchymal cells on the diet, while PPAR delta expression was 6.8-fold decreased. Kupffer cells, however, showed a highly adaptive response with a 2-to 9-fold induction of SR-BI, ABCA1, and ABCG5/G8, and an 82-fold induction in CYP7A1 mRNA expression, respectively. CONCLUSIONS: Heavy lipid loading of parenchymal cells leads to moderate gene expression changes, while Kupffer cells respond in a highly adaptive fashion by stimulating the expression of genes involved in cholesterol metabolism and transport.

J. Hepatol. 42:400-407(2005) [PubMed] [Europe PMC]