Dietary cholesterol affects serum lipids, lipoproteins and LDL metabolism in cynomolgus monkeys in a dose-dependent manner.

To examine the mechanism(s) underlying the cholesterolemic response to dietary cholesterol and saturated fatty acids, low density lipoprotein (LDL) metabolism was studied in two groups of cynomolgus monkeys fed diets containing 30 or 36% of total energy as fat. At each dietary fat level, the same group of monkeys was sequentially fed three dietary cholesterol concentrations as egg yolk in the following sequence: low (0.01 mg/kJ), medium (0.03 mg/kJ) and high (0.05 mg/kJ) for 30, 32 and 24 wk, respectively. Dietary polyunsaturated and monounsaturated fatty acids were the same in the two groups; the 6% difference in fat was due to the saturated fatty acids, 12:0 and 14:0. Serum total cholesterol, LDL cholesterol and LDL apolipoprotein B concentrations increased (P < 0.05) with dietary cholesterol in a dose-dependent manner in both fat groups. These elevations were the result of generally increasing LDL apolipoprotein B production rates, concomitant with reduced LDL apolipoprotein B fractional clearance at the high cholesterol intake. Serum HDL cholesterol and HDL apolipoprotein A-I concentrations were not affected in a consistent manner. These results demonstrate that cynomolgus monkeys are hyperresponsive to dietary cholesterol compared with humans, suggesting that this model may be useful in identifying metabolic and genetic predictors for hyperresponsiveness to dietary cholesterol in humans as well as assessing the metabolic heterogeneity of responses to dietary cholesterol.