EFFECT OF DIETARY LIPIDS ON PLASMA ACTIVITY AND HEPATIC MESSENGER-RNA LEVELS OF CHOLESTERYL ESTER TRANSFER PROTEIN IN HIGH-RESPONDING AND LOW-RESPONDING BABOONS (PAPIO SPECIES)

We compared the effects of dietary cholesterol, type of fat (coconut oil v corn oil), and phenotype (low low-density lipoprotein [LDL] response v high LDL response) on the plasma activity and hepatic mRNA levels of cholesteryl ester transfer protein (CETP). In a crossover design, eight high- and eight low-LDL-responding baboons were fed a series of diets with increasing amounts of cholesterol (0.05, 0.15, 0.45, and 1.35 mg/kcal) with either coconut oil or corn oil. All diets were fed for 7 weeks each. Plasma and lipoprotein cholesterol concentrations, plasma lecithin:cholesterol acyltransferase (LCAT) and CETP activity, and hepatic mRNA levels for CETP and apolipoprotein (apo) A-I were measured after 6 weeks on each diet. Data were analyzed in two steps, ie, the effect of the initial change from chow to 0.05 mg cholesterol with each fat and the effect of the stepwise increase in cholesterol from 0.05 to 1.35 mg/kcal with each fat. High-responding baboons, as expected, showed a more pronounced increment in plasma LDL cholesterol at all dietary cholesterol levels, particularly with coconut oil as the dietary fat. Plasma high-density lipoprotein 2 (HDL2) and HDL3 cholesterol increased as dietary cholesterol increased on both the coconut and corn oil diets, with a greater increase in high-responding baboons than in low-responding baboons. The stepwise increase in dietary cholesterol increased plasma LCAT activity in both high- and low-responding baboons fed the coconut oil diet, but not in those fed the corn oil diet. Dietary cholesterol, regardless of type of fat, increased plasma CETP activity. The increase in LCAT and CETP activities was greater in high-responding baboons than in low-responding baboons. Dietary cholesterol increased hepatic CETP mRNA levels with both types of fat, but the increase was also greater in high responders than in low responders when cholesterol was fed with coconut oil. Thus, dietary cholesterol intake, saturated fatty acid intake, and high-responding phenotype are all associated with increased CETP activity. The increase in CETP activity is probably attributable at least in part and in the coconut oil-fed animals to an increase in the hepatic synthesis and secretion of this protein. This may help to promote a proatherogenic phenotype in these animals. © 1994.