Hepatic acylcoenzyme A: cholesterol acyltransferase activity during diet-induced hypercholesterolemia in cynomolgus...

Acylcoenzyme A: cholesterol acyltransferase (ACAT) activity was studied in hepatic microsomes of cynomolgus monkeys fed either commercial chow or an atherogenic diet of high cholesterol and saturated fat content. ACAT activity (pmol/min per mg protein) was 35 in liver microsomes from control monkeys, and 142 and 161 at 10 and 100 days, respectively, after starting the high cholesterol diet. The cholesterol-fed monkeys had about 1.5-fold increase in cholesterol content of hepatic microsome was compared to control monkeys (94 nmol/mg protein in controls versus 142 nmol/mg protein in the cholesterol fed group). There was no difference between the two groups in microsomal fatty acids in saturated, monoenoic, or polyenoic acid classes. However, the cholesterol-fed monkeys had relatively lower amounts of linoleic acid and higher amounts of arachidonic acid in the microsomes. To determine whether the increased microsomal cholesterol content might be responsible for the increase in ACAT activity, liver microsomes from control monkeys were incubated for 15-120 min with liposomes composed of cholesterol and dipalmitoyl phosphatidylcholine, 2:1 (mol/mol). The microsomal cholesterol content increased from 90 to 128 nmol/mg protein as the incubation progressed. There was a corresponding increase in ACAT activity from 80 to 240 pml/min per mg protein. This observation is consistent with the view that the high hepatic ACAT activity in the cholesterol-fed monkeys is due to the larger amount of cholesterol contained in the microsomes. The increase in hepatic ACAT activity occurs soon after cholesterol feeding is started; this response may be involved in the production of cholesteryl ester-rich lipoprotein by the liver, and thereby may be related to the atherogenic process in these primates.