The kinetic characteristics of inhibition of hepatic cholesterogenesis by lipoproteins of intestinal origin

Abstract

In these studies intestinal lipoproteins were injected intravenously into recipient rats in order to study the kinetic characteristics of cholesterol uptake by the liver cell and inhibition of the cholesterol synthetic pathway. Net cholesterol uptake from circulating intestinal lipoproteins took place only in the liver, and only this tissue manifested inhibition of cholesterol syntheses. Cholesterol uptake by the liver, quantified by a rise in the cholesterol ester content, was a linear function of time and of the amount of lipoprotein cholesterol administered to the animals. Using groups of rats that were either fed cholesterol or injected intravenously with intestinal lipoproteins as a bolus or as a continuous infusion, there was generally a correlation between inhibition of the rate of cholesterol synthesis and the cholesterol ester content of the liver. However, there was no consistent quantitative relationship between these two variables suggesting either that cholesterol ester was not the immediate effector of the inhibition or, alternatively, that there was intracellular localization of the effector at the site of control of the rate-limiting enzyme in the cholesterogenic pathway.