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

We have previously described a novel pathway for the metabolism of HDL subf ractions in which small [2 apolipoprotein (apoA-1) molecules per particle] HDL particles are converted in a unidirectional manner outside the plasma c ompartment to medium (3 apoA-1 molecules per particle) or large (4 apoA-1 m olecules per particle) HDL particles, which are subsequently removed from t he circulation by the liver (Colvin et al. 1999. J. Lipid Res. 40: 1782-179 2; Huggins et al. 2000. J Lipid Res. 41: 384-394). The purpose of the prese nt 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 cataboli sm. Tracer small LpA-I (HDL containing only apoA-1) were isolated, without ultracentrifugation, by gel filtration and immunoaffinity chromatography an d radiolabeled. After injection, the specific activity of apoA-I in small, medium, and large HDL was determined, and the kinetic data were analyzed us ing our previously published multicompartmental model for HDL subfraction m etabolism. We found a significant reduction of apoA-I concentration in medi um HDL in the animals fed n-3 polyunsaturated fat (31.2 +/- 0.7 mg/dl) comp ared with animals fed saturated fat (85.4 +/- 11.9 mg/dl; P = 0.002). The p roduction rates of apoA-1 in small, medium, and large HDL were similar in b oth diet groups; however, there was a significant increase in the fractiona l catabolic rate of apoA-I in medium HDL in the animals fed n-3 polyunsatur ated fat (2.188 +/- 0.501 pools/day) compared with animals fed saturated fa t (0.714 +/- 0.191 pools/day; P = 0.02). We conclude that n-3 polyunsaturat ed fat reduces HDL cholesterol concentration by increasing the fractional c atabolic rate of medium-sized HDL particles in African green monkeys.