CHOLESTEROL ESTERIFICATION IS NOT ESSENTIAL FOR SECRETION OF LIPOPROTEIN COMPONENTS BY HEPG2 CELLS

Hepatic acyl CoA:cholesterol acyltransferase (ACAT) activity may deter mine storage of cholesterol and supply of of cholesteryl esters for th e neutral lipid core of very low density lipoprotein. Inhibition of ch olesterol esterification in HepG2 cells, by the ACAT inhibitor 447C88, partially reduced the secretion of labelled total cholesterol, but th e secretion of apoprotein B mass, and of radiolabelled triacylglycerol and phosphatidylcholine were unaffected. Furthermore, this compound w as shown to substantially deplete the intracellular cholesteryl ester mass without affecting secretion of lipoprotein components. In contras t. the less potent ACAT inhibitor, CL277,082, significantly decreased secretion of labelled triacylglycerol, phosphatidylcholine and total c holesterol, in a manner which mirrored the decreases in secretion of a poB. This study clearly illustrates chat ACAT inhibitors can exert dif ferential effects on secretion of apoB-containing lipoproteins, which do not correlate with their efficacy in inhibiting ACAT, arguing that cholesterol esterification is not essential for Lipoprotein secretion From these cells.