American Journal of Clinical Nutrition, Vol 62, 463S-470S, Copyright © 1995 by The American Society for Clinical Nutrition, Inc

ORIGINAL RESEARCH COMMUNICATIONS

Dietary polyunsaturated fat modifies low-density lipoproteins and reduces atherosclerosis of nonhuman primates with high and low diet responsiveness

LL Rudel, FL Johnson, JK Sawyer, MS Wilson and JS Parks
Department of Comparative Medicine, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, NC 27157, USA.

We tested the hypothesis that an increased content 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 saturated or polyunsaturated fat (40% of energy) as variables. In both species, cholesterol concentrations in whole plasma, LDL, and high-density lipoprotein (HDL) were 20-30% lower when polyunsaturated fat was fed, whereas dietary cholesterol increased LDL cholesterol three- to fourfold. LDL was enriched in cholesteryl oleate when saturated fat and cholesterol were fed. Dietary linoleic acid prevented cholesteryl oleate enrichment and promoted cholesteryl linoleate accumulation in LDL. At the same plasma cholesterol concentration, cynomolgus monkeys had higher LDL cholesterol 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 polyunsaturated 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 atherosclerosis 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.

This article has been cited by other articles:

				I. J. Edwards, I. M. Berquin, H. Sun, J. T. O'Flaherty, L. W. Daniel, M. J. Thomas, L. L. Rudel, R. L. Wykle, and Y. Q. Chen Differential Effects of Delivery of Omega-3 Fatty Acids to Human Cancer Cells by Low-Density Lipoproteins versus Albumin Clin. Cancer Res., December 15, 2004; 10(24): 8275 - 8283. [Abstract] [Full Text] [PDF]

				D. C. Schwenke, L. L. Rudel, M. G. Sorci-Thomas, and M. J. Thomas {alpha}-Tocopherol protects against diet induced atherosclerosis in New Zealand white rabbits J. Lipid Res., November 1, 2002; 43(11): 1927 - 1938. [Abstract] [Full Text] [PDF]

				O. A Matvienko, D. S Lewis, M. Swanson, B. Arndt, D. L Rainwater, J. Stewart, and D L. Alekel A single daily dose of soybean phytosterols in ground beef decreases serum total cholesterol and LDL cholesterol in young, mildly hypercholesterolemic men Am. J. Clinical Nutrition, July 1, 2002; 76(1): 57 - 64. [Abstract] [Full Text] [PDF]

				A. H. Lichtenstein, L. M. Ausman, S. M. Jalbert, M. Vilella-Bach, M. Jauhiainen, S. McGladdery, A. T. Erkkila, C. Ehnholm, J. Frohlich, and E. J. Schaefer Efficacy of a Therapeutic Lifestyle Change/Step 2 diet in moderately hypercholesterolemic middle-aged and elderly female and male subjects J. Lipid Res., February 1, 2002; 43(2): 264 - 273. [Abstract] [Full Text] [PDF]

				Y. Fusegawa, K. L. Kelley, J. K. Sawyer, R. N. Shah, and L. L. Rudel Influence of dietary fatty acid composition on the relationship between CETP activity and plasma lipoproteins in monkeys J. Lipid Res., November 1, 2001; 42(11): 1849 - 1857. [Abstract] [Full Text] [PDF]

				M. Merkel, W. Velez-Carrasco, L. C. Hudgins, and J. L. Breslow Compared with saturated fatty acids, dietary monounsaturated fatty acids and carbohydrates increase atherosclerosis and VLDL cholesterol levels in LDL receptor-deficient, but not apolipoprotein E-deficient, mice PNAS, October 16, 2001; (2001) 231490498. [Abstract] [Full Text] [PDF]

				J. W. Furbee Jr., O. Francone, and J. S. Parks Alteration of plasma HDL cholesteryl ester composition with transgenic expression of a point mutation (E149A) of human LCAT J. Lipid Res., October 1, 2001; 42(10): 1626 - 1635. [Abstract] [Full Text] [PDF]

				W. T. Cefalu, J. G. Terry, M. J. Thomas, T. M. Morgan, I. J. Edwards, L. L. Rudel, J. W. Kemnitz, and R. Weindruch In Vitro Oxidation of Low-Density Lipoprotein in Two Species of Nonhuman Primates Subjected to Caloric Restriction J. Gerontol. A Biol. Sci. Med. Sci., July 1, 2000; 55(7): 355B - 361. [Abstract] [Full Text]

				T. P. Carr, G. Cai, J.-Y. Lee, and C. L. Schneider Cholesteryl Ester Enrichment of Plasma Low-Density Lipoproteins in Hamsters Fed Cereal-Based Diets Containing Cholesterol Experimental Biology and Medicine, January 1, 2000; 223(1): 96 - 101. [Abstract] [Full Text]

				L. Calleja, M. A. Paris, A. Paul, E. Vilella, J. Joven, A. Jimenez, G. Beltran, M. Uceda, N. Maeda, and J. Osada Low-Cholesterol and High-Fat Diets Reduce Atherosclerotic Lesion Development in ApoE-Knockout Mice Arterioscler. Thromb. Vasc. Biol., October 1, 1999; 19(10): 2368 - 2375. [Abstract] [Full Text] [PDF]

				A. Tall, C. Welch, D. Applebaum-Bowden, and M. Wassef Interaction of Diet and Genes in Atherogenesis Report of an NHLBI Working Group Arterioscler. Thromb. Vasc. Biol., November 1, 1997; 17(11): 3326 - 3331. [Abstract] [Full Text]

				A. T.K. Singh, D. L. Rainwater, C. M. Kammerer, R. M. Sharp, M. Poushesh, W. R. Shelledy, and J. L. VandeBerg Dietary and Genetic Effects on LDL Size Measures in Baboons Arterioscler. Thromb. Vasc. Biol., December 1, 1996; 16(12): 1448 - 1453. [Abstract] [Full Text]

				L. L. Rudel, J. S. Parks, and J. K. Sawyer Compared With Dietary Monounsaturated and Saturated Fat, Polyunsaturated Fat Protects African Green Monkeys From Coronary Artery Atherosclerosis Arterioscler. Thromb. Vasc. Biol., December 1, 1995; 15(12): 2101 - 2110. [Abstract] [Full Text]

				M. Merkel, W. Velez-Carrasco, L. C. Hudgins, and J. L. Breslow Compared with saturated fatty acids, dietary monounsaturated fatty acids and carbohydrates increase atherosclerosis and VLDL cholesterol levels in LDL receptor-deficient, but not apolipoprotein E-deficient, mice PNAS, November 6, 2001; 98(23): 13294 - 13299. [Abstract] [Full Text] [PDF]