HIGH-FAT, HIGH CHOLESTEROL DIETS ALTER LOW-DENSITY-LIPOPROTEIN SIZE AND BINDING-AFFINITY IN MONKEYS

The purpose of this study was to examine the effects of various dietar y fats on low density lipoprotein (LDL) binding in an in vitro system where receptor number is not regulated. Cynomolgus monkeys were fed di ets containing 37% of energy from fat, with various degrees of saturat ion, and 0.4 mg/kcal cholesterol or low-fat (13% of energy), low chole sterol (0.03 mg/kcal) chow. Plasma LDL was isolated after 16 weeks. Th e fatty acid composition of LDL showed enrichment corresponding to the dietary fats consumed, and the high fat, high cholesterol diets produ ced marked hypercholesterolemia compared to chow feeding. Of those fed the high fat diets, monkeys fed the fish oil diet had the highest LDL cholesterol concentrations, 13.25 +/- 0.77 mmol/l, while those fed th e safflower oil diet had the lowest, 7.51 +/- 3.31. LDL from chow fed monkeys had the lowest binding affinity; the K-d was 26.2 +/- 8.7 mu g /ml, nearly twice that of the high fat diets (P = 0.003). No significa nt differences in binding were found between the different high fat di ets, although there was a trend toward lower affinity in the diets enr iched in polyunsaturated fat. LDL size was affected by diet with chow fed monkeys having the smallest average LDL, 259.3 +/- 1.7 Angstrom co mpared to the other groups (P = 0.03). Monkeys fed the fish oil diet t ended to have smaller LDL, but this was not significantly different fr om the other high fat diets. Binding affinity was correlated with LDL size, r = 0.54, P < 0.01. LDL composition, as measured by apo B/choles terol ratio, was altered by feeding a high fat, high cholesterol diet. The ratio was reduced in the LDL samples from monkeys fed the high fa t diets compared to those fed chow, but this ratio was not significant ly correlated with binding. Thus, it appears that increasing dietary f at and cholesterol intake increases LDL size and binding affinity, suc h that LDL metabolism may be altered independently from effects on rec eptor number; the type of dietary fat does not seem to influence this process when fat and cholesterol content is very high. (C) 1997 Elsevi er Science Ireland Ltd.