title: In vivo regulation of hepatic lipase activity and mRNA levels by diets which modify cholesterol influx to the liver.
abstract: The aim of this study was to assess whether diets enriched in cholesterol, sodium cholate and drugs known to modify liver cholesterol biosynthesis can modulate hepatic lipase (H-TGL) expression and activity in vivo. Female lean Zucker rats, known to be good responders to cholesterol, were fed for 7 days with a control C diet or the C diet supplemented (w/w) with either 2% cholesterol, 0.5% sodium cholate, 2% cholestyramine or simvastatin (0.1%) added to the cholestyramine diet or given by gavage (10 mg/rat) for 3 days. H-TGL activity decreased by 34% with cholesterol, and by 27% when both cholesterol and cholate were administered to the rats. Under these conditions, H-TGL mRNA decreased by 34% and 87%, respectively. The sharp decrease in H-TGL expression was associated with a strong increase in cholesteryl ester in total liver and in the liver microsome fraction. H-TGL activity decreased by 33% with cholestyramine and the mRNA level decreased by 47%. Simvastatin lowered H-TGL activity by 55% when added to the cholestyramine diet, probably because of a reduction in food intake. When administrated by gavage, simvastatin increased both the H-TGL activity (by 28%) and mRNA (by 23%). These variations may be linked to the availability of mevalonate-derived sterol and non-sterol products.
authors.affiliation: Laboratoire de Recherches sur la Physiopathologie de la Nutrition, INSERM U 177, Paris, France.
authors.forename: F
authors.initials: F
authors.lastname: Benhizia
authors.forename: D
authors.initials: D
authors.lastname: Lagrange
authors.forename: M I
authors.initials: MI
authors.lastname: Malewiak
authors.forename: S
authors.initials: S
authors.lastname: Griglio
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002784:Cholesterol / Q000378:metabolism*; D002791:Cholesterol, Dietary / Q000008:administration & dosage / Q000494:pharmacology*; D002792:Cholestyramine Resin / Q000008:administration & dosage / Q000494:pharmacology; D019826:Cholic Acid; D002793:Cholic Acids / Q000008:administration & dosage / Q000494:pharmacology; D004032:Diet; D005260:Female; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism; D008049:Lipase / Q000235:genetics / Q000378:metabolism*; D050356:Lipid Metabolism; D008055:Lipids / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D008148:Lovastatin / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D011924:Rats, Zucker; D019821:Simvastatin
chemical_list: D002791:Cholesterol, Dietary; D002793:Cholic Acids; D008055:Lipids; D012333:RNA, Messenger; D002792:Cholestyramine Resin; D002784:Cholesterol; D008148:Lovastatin; D019821:Simvastatin; D006903:Hydroxymethylglutaryl CoA Reductases; D008049:Lipase; D019826:Cholic Acid