Dietary fat saturation and hepatic acylcoenzyme A:cholesterol acyltransferase activity. Effect of n-3 polyunsaturated and long-chain saturated fat.

The acylcoenzyme A:cholesterol acyltransferase (ACAT) activity in liver microsomes from rats fed a diet containing 14% menhaden oil (Mp) for 11 days was 117% higher than that in microsomes from rats fed a corresponding diet containing 14% cocoa butter (Ms). There were no differences in the cholesterol and phospholipid contents of Mp and Ms or in the activities of palmitoyl coenzyme A hydrolase and NADPH cytochrome c reductase. NADPH-dependent lipid peroxidation was higher in Mp, whereas glucose 6-phosphatase activity was higher in Ms. These findings indicate that the ACAT response to differences in dietary fat saturation is not due to a nonspecific effect of these diets on microsomal enzymes. When 1% cholesterol was added to the diets, the cholesterol content and ACAT activity of both microsomal preparations increased, but the ACAT activity of Mp remained 60% higher than that of Ms. Addition of cholesterol by incubation of the microsomes with liposomes also increased ACAT activity. At corresponding cholesterol contents, however, the ACAT activity of Mp remained 50% to 70% above that of Ms. There was no difference in the plasma cholesterol concentration in the two groups of rats, indicating that the ACAT effect probably is not due to a difference in the amount of circulating cholesterol available to the liver. Mp contained 40% more polyunsaturated fatty acids and five times more n-3 polyunsaturates than Ms. These findings suggest that the increase in ACAT activity in Mp is due, at least in part, to the difference in the fatty acid composition of the microsomes.