The effect of inhibition of cholesterol esterification on the fate of cholesterol derived from HDL in rat hepatocyte monolayers

Rat HDL 2 is known to stimulate bile acid synthesis in rat hepatocyte monolayers. The intracellular fate of the cholesterol derived from the HDL 2 was studied using the inhibitor of cholesterol esterification, Sandoz compound 58-035. Rat HDL 2 added to rat hepatocyte monolayers caused a stimulation of cholesterol esterification of 32%. This stimulation could be inhibited by 58-035. A small significant increase in bile acid synthesis was also observed in cells in the presence of HDL 2, confirming our earlier observations. 58-035 prevented this increase. These observations imply that cholesterol entering the cell from HDL 2 is first esterified and can only enter the substrate pool for bile acid synthesis after subsequent intracellular hydrolysis.