Lipid composition and physical state effects on cellular cholesteryl ester clearance.

The influence of lipid composition and physical state on the rate of cholesteryl ester clearance from cytoplasmic inclusions has been investigated. Our findings demonstrate that the increased rate of clearance correlates with an increased cellular triglyceride content and a more fluid cholesteryl ester physical state. Cultured rat hepatoma cells were induced to accumulate esterified cholesterol in a smectic liquid-crystalline state by exposure to free cholesterol-rich phospholipid dispersions. Addition of cis-unsaturated fatty acids to this loading medium (either oleate, linoleate, linolenate, or eicosadienoate) resulted in a substantial increase in cellular triglyceride content (greater than 7 times non-fatty acid-treated), cellular cholesteryl esters in a liquid state, and a rate of cholesteryl ester clearance twice that of control (approximately 34% versus 17% in 12 h). In studies with oleic acid, storage of cellular cholesteryl esters in a liquid state was found to be dependent on the presence of triglycerides, and the rate at which these cells hydrolyzed cholesteryl esters was proportional to triglyceride levels. Cells exposed to either linoleic or linolenic acid hydrolyzed cholesteryl esters at the faster rate, but in contrast to findings with oleate and eicosadienoate, the storage of cholesteryl esters in a liquid state may also be a consequence of the modified fatty acyl composition of the cholesteryl esters themselves. Addition of a saturated fatty acid (palmitate) or a fatty acid with a trans-double bond (elaidate) to the cholesterol loading media had little effect on cellular triglyceride content, cholesteryl ester physical state, or the rate of cholesteryl ester clearance.