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.