Genetic factors influence the atherogenic response of lipoproteins to dietary fat and cholesterol in nonhuman primates.

Abstract

Comparative studies of diet responsiveness have carried out in five different old world primate species, including African green, stumptail, rhesus, patas, and cynomolgus monkeys. The dietary variables examined were level of cholesterol (0.03 and 0.8 mg cholesterol/kcal) and type of fat (enriched in saturated vs. n-6 polyunsaturated fatty acids). In all cases, hypercholesterolemia resulted from the high cholesterol diet, making it possible to identify low, moderate, and high responding species. Polyunsaturated vs. saturated fat effects to lower plasma cholesterol did not appear to be remarkably species specific, except for the more pronounced response in African green monkeys. For low-density lipoprotein (LDL) cholesterol concentrations, African green monkeys were the lowest responding species and cynomolgus monkeys were the highest. LDL particle enlargement was least in African green monkeys and highest in rhesus and cynomolgus monkeys. High-density lipoprotein (HDL) cholesterol levels were similar among species on the low cholesterol diet, but decreased when the high cholesterol diet was fed in all species except African green monkeys, where HDL increased with added dietary cholesterol. Coronary artery atherosclerosis developed only when the high cholesterol diet was fed, occurred more rapidly, and became more extensive in cynomolgus compared to African green monkeys. Polyunsaturated fat limited the amount of atherosclerosis that developed in both species. Genetic factors regulating the response to dietary cholesterol in degree of hyperlipoproteinemia, cholesterol distribution among lipoproteins, LDL particle size, and HDL cholesterol concentration were characteristically unique among different primate species. The effects of lipoproteins were well correlated with the extent of coronary artery atherosclerosis.