Regulation of cholesteryl ester metabolism in the hamster liver

Neutral cholesteryl ester hydrolase activity has been described in the cytosolic and microsomal fraction of rat liver, but the relationship of these activities to other parameters of hepatic cholesterol metabolism is not known. We have studied this in the hamster by manipulating the flux of cholesterol across the liver by dietary modifications. A bile acid sequestrant was used to stimulate LDL receptor activity and hence flux of cholesterol into the liver. A cholesterol-rich diet caused a hypercholesterolaemia and substantial uptake of cholesterol and deposition in the liver. Hypercholesterolaemia was also induced by a saturated fat-rich diet, but in contrast this reduced the flux of cholesterol into the liver. Animals were fed these diets for 1 week and then the livers removed and enzyme activities determined. These were 3-hydroxy-3-methylglutaryl-CoA reductase, cholesterol 7 alpha-hydroxylase, acyl-CoA: cholesterol acyltransferase, microsomal cholesteryl ester hydrolase and cytosolic cholesteryl ester hydrolase. Feeding the bile acid sequestrant increased the hydrolysis of cholesteryl ester in the liver over its synthesis. In contrast, both fat feeding and cholesterol feeding caused a reduction in the relative rate of hydrolysis of cholesteryl ester compared with synthesis. This was particularly marked with the cholesterol-rich diet. These results show that the hydrolysis of cholesteryl ester in hamster liver responds to dietary manipulation in a way that reflects the needs of the cell for cholesterol or the presence of an excess. It is suggested that a metabolically significant cholesteryl ester cycle may operate in the liver to a greater extent that had previously been thought.