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LDL Receptor Activity Is Down-Regulated Similarly by a Cholesterol-Containing Diet High in Palmitic Acid or High in Lauric and Myristic Acids in Cynomolgus Monkeys^1,2,

Center for Cardiovascular Disease Control, Department of Clinical Sciences, University of Massachusetts-Lowell, Lowell, MA 01854

To determine the mechanisms whereby diets differing widely in fatty acid composition affect plasma LDL cholesterol and apolipoprotein B concentrations, LDL kinetics and receptor- and nonreceptor-mediated LDL catabolism were investigated in 27 cynomolgus monkeys fed diets containing 0.05 mg cholesterol/kJ and 40% fat energy as corn oil alone (unsaturated fat diet rich in oleic and linoleic acids), nonhydrogenated coconut oil alone (saturated fat diet, rich in lauric and myristic acids) or an oil blend (rich in palmitic acid). Consumption of the oil blend and saturated fat diets significantly elevated total cholesterol, LDL cholesterol and apolipoprotein B concentrations relative to the unsaturated fat diet and the saturated fat diet significantly increased plasma total cholesterol and LDL cholesterol compared with the oil blend diet. However, despite the greater increases in plasma total cholesterol, LDL cholesterol and apolipoprotein B in the saturated fat vs. the oil blend dietary group, the receptor-mediated LDL fractional catabolic rate was comparable in the oil blend and saturated fat diet groups. In addition, consumption of the oil blend or saturated fat diet increased the production rate of LDL apolipoprotein B and nonreceptor-mediated LDL apolipoprotein B transport (disposal) relative to the unsaturated fat diet. Our data, therefore, suggest that consumption of the oil blend or saturated fat diet elevated plasma total cholesterol and LDL cholesterol relative to the unsaturated fat diet, and the oil blend diet abundant in palmitic acid seems to have down-regulated the LDL receptor as much as a more saturated fat diet abundant in lauric and myristic acids.

KEY WORDS: • low density lipoprotein receptors • saturated fatty acids • apolipoprotein B metabolism • high density lipoprotein • cynomolgus monkeys

¹ Supported in part by National Institutes of Health grant R01HL39385 (RJN).

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 and reprint requests should be addressed.

Manuscript received 15 September 1994. Revision accepted 17 February 1995.