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Journal of Lipid Research, Vol. 42, 1457-1466, September 2001
Copyright © 2001 by Lipid Research, Inc.

Original Article

Dietary n-3 polyunsaturated fat increases the fractional catabolic rate of medium-sized HDL particles in African green monkeys

Correspondence to: Kevin W. Huggins, Present address: Department of Pathology and Laboratory Medicine, University of Cincinnati College of Medicine, Cincinnati, OH 45267.

We have previously described a novel pathway for the metabolism of HDL subfractions in which small [2 apolipoprotein (apoA-I) molecules per particle] HDL particles are converted in a unidirectional manner outside the plasma compartment to medium (3 apoA-I molecules per particle) or large (4 apoA-I molecules per particle) HDL particles, which are subsequently removed from the circulation by the liver (Colvin et al. 1999. J. Lipid Res. 40: 1782;–1792; Huggins et al. 2000. J. Lipid Res. 41: 384;–394). The purpose of the present study was to determine whether the reduction in concentration of medium HDL in African green monkeys consuming n-3 polyunsaturated versus saturated fat diets resulted from decreased in vivo production or increased catabolism. Tracer small LpA-I (HDL containing only apoA-I) were isolated, without ultracentrifugation, by gel filtration and immunoaffinity chromatography and radiolabeled. After injection, the specific activity of apoA-I in small, medium, and large HDL was determined, and the kinetic data were analyzed using our previously published multicompartmental model for HDL subfraction metabolism. We found a significant reduction of apoA-I concentration in medium HDL in the animals fed n-3 polyunsaturated fat (31.2 ± 0.7 mg/dl) compared with animals fed saturated fat (85.4 ± 11.9 mg/dl; P = 0.002). The production rates of apoA-I in small, medium, and large HDL were similar in both diet groups; however, there was a significant increase in the fractional catabolic rate of apoA-I in medium HDL in the animals fed n-3 polyunsaturated fat (2.188 ± 0.501 pools/day) compared with animals fed saturated fat (0.714 ± 0.191 pools/day; P = 0.02).

We conclude that n-3 polyunsaturated fat reduces HDL cholesterol concentration by increasing the fractional catabolic rate of medium-sized HDL particles in African green monkeys. — Huggins, K. W., P. L. Colvin, E. R. Burleson, K. Kelley, J. K. Sawyer, P. H. R. Barrett, L. L. Rudel, and J. S. Parks. Dietary n-3 polyunsaturated fat increases the fractional catabolic rate of medium-sized HDL particles in African green monkeys. J. Lipid Res. 2001. 42: 1457;–1466.

Supplementary key words: fish oil, LpA-I, apolipoprotein A-I, PUFA, non-human primates, saturated fat, in vivo catabolism

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