In vivo regulation of hepatic lipase activity and mRNA levels by diets which modify cholesterol influx to the liver

• Published in: Biochimica et biophysica acta Vol. 1211; no. 2; pp. 181 - 188
• Main Authors: Benhizia, F, Lagrange, D, Malewiak, M.I, Griglio, S
• Format: Journal Article
• Language: English
• Published: Netherlands 03.03.1994
• Subjects: Animals; Body Weight - drug effects; cholesterol; Cholesterol - metabolism; Cholesterol, Dietary - administration & dosage; Cholesterol, Dietary - pharmacology; Cholestyramine Resin - administration & dosage; Cholestyramine Resin - pharmacology; Cholic Acid; Cholic Acids - administration & dosage; Cholic Acids - pharmacology; colestyramine; Diet; drug therapy; Female; Hydroxymethylglutaryl CoA Reductases - metabolism; Lipase - genetics; Lipase - metabolism; Lipid Metabolism; Lipids - blood; liver; Liver - drug effects; Liver - enzymology; Liver - metabolism; Lovastatin - administration & dosage; Lovastatin - analogs & derivatives; Lovastatin - pharmacology; messenger RNA; Rats; Rats, Zucker; regulation; RNA, Messenger - metabolism; Simvastatin; triacylglycerol lipase
• ISSN: 0006-3002; 1878-2434

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.