title: Diet induced regulation of genes involved in cholesterol metabolism in rat liver parenchymal and Kupffer cells.
abstract: 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.
authors.affiliation: 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
authors.forename: Menno
authors.initials: M
authors.lastname: Hoekstra
authors.forename: Ruud
authors.initials: R
authors.lastname: Out
authors.forename: Johan Kar
authors.initials: JK
authors.lastname: Kruijt
authors.forename: Miranda
authors.initials: M
authors.lastname: Van Eck
authors.forename: Theo J C
authors.initials: TJ
authors.lastname: Van Berkel
mesh_terms: 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
chemical_list: D002791:Cholesterol, Dietary; D017931:DNA Primers; D008055:Lipids; D002784:Cholesterol; D019826:Cholic Acid