Production of apolipoprotein E-rich LDL by the liver. The effect of dietary cholesterol and some lipid lowering agents.
We reported previously that cholesterol feeding induced an increase in hepatic secretion of VLDL and a decrease in that of LDL, especially LDL-apo B100, using monkey liver perfusion. In the present study we conducted rat liver perfusion using the HMG Co A reductase inhibitor (CS-514) and Kampo medicine (Daisaikoto) to elucidate the mechanism of the effect of dietary cholesterol on hepatic lipoprotein and apolipoprotein synthesis. Although the secretion of VLDL was increased by cholesterol feeding, that of LDL and especially of apo B100 of LDL were markedly decreased, and apo E of the LDL was increased as observed in the monkey liver perfusion experiments. The effect of CS-514 was clearly different from the effect of dietary cholesterol in spite of the suppression of hepatic cholesterogenesis which was comparable to that induced by cholesterol feeding, suggesting that the decrease in secretion of LDL-apo B100 induced by the dietary cholesterol is not due to suppressed cholesterogenesis. Daisaikoto, which was added to the diet together with cholesterol, diminished the effects of dietary cholesterol on the plasma and hepatic cholesterol levels. When the liver treated with Daisaikoto was perfused, the effect of dietary cholesterol on the production of lipoprotein and apolipoprotein was markedly diminished. This evidence indicates that the decrease in LDL-apo B100 and the increase in apo E were mediated by the hepatic cholesterol level.
Teramoto
T
T
First Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.
Matsushima
T
T
Horie
Y
Y
Watanabe
T
T
D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D001057:Apolipoproteins E / Q000096:biosynthesis*; D002791:Cholesterol, Dietary / Q000494:pharmacology*; D004365:Drugs, Chinese Herbal / Q000494:pharmacology; D006538:Heptanoic Acids / Q000494:pharmacology*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008077:Lipoproteins, LDL / Q000096:biosynthesis*; D008079:Lipoproteins, VLDL / Q000096:biosynthesis; D008099:Liver / Q000378:metabolism*; D008297:Male; D009281:Naphthalenes / Q000494:pharmacology*; D017035:Pravastatin; D051381:Rats; D011919:Rats, Inbred Strains
D000924:Anticholesteremic Agents; D001057:Apolipoproteins E; D002791:Cholesterol, Dietary; D004365:Drugs, Chinese Herbal; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008077:Lipoproteins, LDL; D008079:Lipoproteins, VLDL; D009281:Naphthalenes; C051121:daisaikoto; D017035:Pravastatin