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A Diet Enriched in Monounsaturated Fats Decreases Low Density Lipoprotein Concentrations in Cynomolgus Monkeys by a Different Mechanism than does a Diet Enriched in Polyunsaturated Fats^1,2,

Cardiovascular Research Laboratory, Department of Clinical Sciences, University of Massachusetts-Lowell, Lowell, MA ^* Lipid Metabolism Laboratory, USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA

To determine the mechanisms whereby dietary fat saturation influences LDL cholesterol and apolipoprotein B concentrations, 10 cynomolgus monkeys were fed each of three experimental diets enriched in saturated, monounsaturated or polyunsaturated fatty acids in a crossover design consisting of three 13-wk periods. Each diet contained 30% of energy as fat with 0.05 mg cholesterol/kJ and differed solely by the isocaloric substitution of fatty acids as 60% of total fat energy. The replacement of dietary saturated fatty acids with either mono- or polyunsaturated fatty acids resulted in significant reductions of plasma total cholesterol (-17% and -30%, respectively), HDL cholesterol (-32% and -41%, respectively), apoA-1 (-37% and -44%, respectively), and apolipoprotein B (-28% and -36%, respectively) concentrations. Additionally, when dietary polyunsaturated fatty acids were substituted for saturated fatty acids, a 27% reduction in VLDL + LDL cholesterol was significant. Metabolic experiments suggested that the significantly reduced concentrations of apolipoprotein B observed during the monounsaturated and polyunsaturated fatty acid phases relative to the saturated fatty acid phase could not be entirely explained by changes in LDL apolipoprotein B clearance but rather were likely due to decreased LDL apolipoprotein B production rates. However, enhanced LDL apolipoprotein B catabolism accounted for the even greater reductions in VLDL + LDL cholesterol and apolipoprotein B concentrations observed during the polyunsaturated fatty acid phase vs. the monounsaturated fatty acid phase. Our data suggest that monounsaturated and polyunsaturated fatty acids lower apolipoprotein B concentrations by distinct mechanisms, with polyunsaturated fatty acids affecting LDL apolipoprotein B catabolism as well as production.

KEY WORDS: • apolipoprotein B • low density lipoproteins • fatty acids • metabolism • cynomolgus monkeys

¹ Supported by grant R01 HL 39385 from the National Institutes of Health to R.J.N. and by contract 53-3K-06-10 from the U.S. Department of Agriculture Research Service to E.J.S. Margaret E. Brousseau was a doctoral candidate at the Tufts University School of Nutrition.

² The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 USC section 1734 solely to indicate this fact.

³ To whom correspondence should be addressed.

Manuscript received 28 October 1992. Initial review completed 23 December 1992. Revision accepted 9 July 1993.