Diet induced regulation of genes involved in cholesterol metabolism in rat liver parenchymal and Kupffer cells.
OBJECTIVE
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.
Hoekstra
Menno
M
Division of Biopharmaceutics, Leiden/Amsterdam Center for Drug Research, Gorlaeus Laboratories, Leiden University, P.O. Box 9502, 2300 RA Leiden, The Netherlands. hoekstra@lacdr.leidenuniv.nl
Out
Ruud
R
Kruijt
Johan Kar
JK
Van Eck
Miranda
M
Van Berkel
Theo J C
TJ
D000818:Animals; D001483:Base Sequence; D002784:Cholesterol / Q000378:metabolism; D002791:Cholesterol, Dietary; D019826:Cholic Acid / Q000494:pharmacology; D017931:DNA Primers; D004036:Diet, Atherogenic; D005786:Gene Expression Regulation / Q000502:physiology*; D007728:Kupffer Cells / Q000473:pathology / Q000502:physiology*; D008055:Lipids / Q000097:blood; D008099:Liver / Q000473:pathology / Q000502:physiology*; D016133:Polymerase Chain Reaction; D051381:Rats
D002791:Cholesterol, Dietary; D017931:DNA Primers; D008055:Lipids; D002784:Cholesterol; D019826:Cholic Acid