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

We have previously described a novel pathway for the metabolism of HDL subfractions in which small (2 apolipo- protein (apoA-I) molecules per particle) HDL particles are converted in a unidirectional manner outside the plasma com- partment to medium (3 apoA-I molecules per particle) or large (4 apoA-I molecules per particle) HDL particles, which are sub- sequently 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 me- dium HDL in African green monkeys consuming n-3 polyunsat- urated 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 ultracen- trifugation, by gel filtration and immunoaffinity chromatogra- phy 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 me- dium 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; how- ever, there was a significant increase in the fractional catabolic rate of apoA-I in medium HDL in the animals fed n-3 polyun- saturated fat (2.188 � 0.501 pools/day) compared with ani- mals fed saturated fat (0.714 � 0.191 pools/day; P � 0.02). We conclude that n-3 polyunsaturated fat reduces HDL choles- terol 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.