EFFECT OF DIETARY-FAT SATURATION AND CHOLESTEROL ON LDL COMPOSITION AND METABOLISM - INVIVO STUDIES OF RECEPTOR AND NONRECEPTOR-MEDIATED CATABOLISM OF LDL IN CEBUS MONKEYS

The mechanism(s) by which polyunsaturated fats reduce low density lipoprotein (LDL) cholesterol and apolipoprotein (apo) B were investigated in 20 cebus monkeys (Cebus albifrons) fed diets containing corn oil or coconut oil as fat (31% of calories) with or without dietary cholesterol (0.1% by weight) for 3 to 10 years. Coconut-oil feeding compared to corn-oil feeding resulted in significant increases in levels of plasma total cholesterol (176%), very low density lipoprotein (VLDL)-LDL cholesterol (236%), high density lipoprotein (HDL) cholesterol (148%), apo B (78%), and apo A-l (112%). The addition of dietary cholesterol to corn oil compared to corn oil alone resulted in smaller, but significant, increases in levels of total cholesterol (44%), HDL cholesterol (40%), and apo A-l (33%). Although the increases in VLDL-LDL cholesterol were of similar magnitude (52%), they barely failed to reach statistical significance (p<0.08), while the changes in apo B levels were negligible. The addition of dietary cholesterol to coconut oil, compared to coconut oil alone, resulted in no significant changes in lipoprotein cholesterol or apoproteins, although levels of VLDL-LDL cholesterol and apo B values increased 22% and 16%, respectively. Although hepatic free cholesterol content was not altered by diet, coconut-oil compared to corn-oil feeding resulted in significant increases in hepatic cholesteryl esters (236%) and triglycerides (325%), the latter increasing still further when dietary cholesterol was added to coconut oil (563%). To further assess the effects of these dietary changes on LDL metabolism, radioiodinated normal and glucosylated LDL kinetics were performed. The production rate of LDL apo B was not altered by diet. With corn-oil feeding, 63% of LDL catabolism was via the receptor-mediated pathway. Coconut-oil compared to corn-oil feeding resulted in a 50% decrease in receptor-mediated LDL apo B fractional catabolic rate (FCR) and a 27% reduction in nonreceptor-mediated LDL apo B FCR. The addition of dietary cholesterol to corn oil, compared to corn oil alone, resulted in no significant effect on LDL apo B catabolism. The addition of dietary cholesterol to coconut oil, compared to coconut oil alone, was associated with no significant change in nonreceptor catabolism of LDL apo B but with a 58% decrease in receptor-mediated catabolism of LDL (p<0.059). The diet-induced alterations of LDL catabolism were significantly correlated with hepatic lipids, which were enriched in saturated fatty acids. These data indicate that the degree of dietary fatty acid saturation induced greater changes in plasma lipoprotein levels and LDL metabolism than did dietary cholesterol. The significant degree of correlation between LDL catabolism and the accumulation of hepatic lipids enriched in saturated fatty acids suggests that dietary modifications leading to alterations in membrane fatty acyl content may also influence cellular LDL metabolism.