Am J Clin Nutr 1995;62:463S-70S. Printed in USA. © 1995 American Society for Clinical Nutrition 4635 Dietary polyunsaturated fat modifies low-density lipoproteins and reduces atherosclerosis of nonhuman primates with high and low diet responsiveness3 Lawrence L Rudel, Fred L Johnson, Janet K Sawyer, Martha S Wilson, and John S Parks ABSTRACT We tested the hypothesis that an increased con- tent of n-6 polyunsaturated fatty acids (principally linoleic acid) in an atherogenic diet of nonhuman primates would decrease atherosclerosis by modifying the composition and decreasing the concentration of plasma low-density lipoprotein (LDL). A species readily susceptible to diet-induced atherosclerosis (cynomolgus monkey) was compared with a less-susceptible species (African green monkey) with dietary cholesterol concentration and satu- rated or polyunsaturated fat (40% of energy) as variables. In both species, cholesterol concentrations in whole plasma, LDL, and high-density bipoprotein (HDL) were 20-30% lower when poly- unsaturated fat was fed, whereas dietary cholesterol increased LDL cholesterol three- to fourfold. LDL was enriched in chobestenyl oleate when saturated fat and cholesterol were fed. Dietary binoleic acid prevented chobesteryl oleate enrichment and promoted cho- lesteryb binobeate accumulation in LDL. At the same plasma cho- lesterol concentration, cynomolgus monkeys had higher LDL cho- lesterol and lower HDL-cholesterol concentrations than did African green monkeys. LDL particle size was significantly (P < 0.001) larger in the group of cynomolgus monkeys fed pobyunsat- urated fat but tended to be smaller in African green monkeys fed polyunsaturated fat. Dietary polyunsaturated fat protected against coronary artery atherosclerosis in both species. Thus, LDL particle size, per se, was not atherogenic; instead, coronary artery atheno- sclerosis and cholesteryl oleate enrichment of LDL were more highly correlated. This outcome suggests that information about LDL composition may be more important for understanding the pathogenesis of atherosclerosis than previously suspected. Am J Clin Nutr 1995;62:463S-70S. KEY WORDS Cholesterol, polyunsaturated fat, lipopro- tein metabolism, dietary responsiveness, coronary artery atherosclerosis, nonhuman primates INTRODUCTION The effects of dietary cholesterol and type of fat on coronary heart disease have been the focus of much attention. In general, recommendations have been to limit the amount of total and saturated fat in the diet, replace saturated with polyunsaturated fat, and limit the amount of dietary cholesterol. Studies from the US Department of Agriculture indicate that Americans have been better at increasing the amount of vegetable oil in our diet than in decreasing the percentage of energy intake as fat (1). Decreased saturated fatty acid and increased binoleic acid intakes may be components of the overall 50% reduction in coronary heart disease rates that has occurred over the past two decades in the United States (2). A significant body of evidence demonstrates that, for linoleic acid, accumulation in adipose tissue (3-5) and enrichment in plasma cholesteryl esters (6-8) are both factors associated with decreased rates of premature complications of coronary heart disease. Whereas the mechanism of the protection offered by linoleic acid is not clearly established, it has been well documented that an in- creased content of this essential fatty acid in the diet is asso- ciated with bower plasma cholesterol concentrations (9, 10). Documentation exists that ingestion of diets enriched in mdi- vidual fatty acids leads to modified fatty acid compositions in plasma bow-density-bipoprotein (LDL) cholesterol and in many plasma membrane lipids (1 1). The modification of LDL lipids to include more linoleic acid leads to increased rates of LDL oxidation in a test tube (12-15). Such changes have led to suggestions that people would benefit from decreasing the amount of linoleic acid in their diet and therefore in their LDL particles (16, 17) to prevent LDL oxidation. This suggestion is paradoxical in light of the docu- mented association between linoleic acid in plasma cholesteryl esters and decreased coronary heart disease as indicated above (6-8). A specific robe of LDL oxidation in atherosclerosis has yet to be demonstrated although it is the subject of intense speculation (18). However, a beneficial role for dietary li- noleate in the reduction of coronary artery atherosclerosis has been experimentally established (19, 20). The role of linoleic acid in coronary heart disease is not yet fully defined and we must remain open-minded until more aspects of this relation are determined. The goal of the present studies was to identify whether consistently beneficial effects of polyunsaturated fat rich in linoleic acid on lipoprotein metabolism would be demonstrable in two species of nonhuman primates that are more and less 1 From the Departments of Comparative Medicine and Biochemistry, Bowman Gray School of Medicine of Wake Forest University, Winston- Salem, NC, and Burroughs Wellcome Company, Division of Pharmacol- ogy, Research Triangle Park, NC. 2 Supported by NIH grants HL-14164, HL-24736, and HL-49373. 3 Address reprint requests to LL Rudel, Department of Comparative Medicine, Bowman Gray School of Medicine of Wake Forest University, Winston-Salem, NC 27157. by guest on July 13, 2011 www.ajcn.org Downloaded from