Metabolism of larger high density lipoproteins accumulating in some families of baboons fed a high cholesterol and high saturated fat diet.

Abstract

Progeny of certain baboon sires accumulate lipoproteins in high density lipoprotein-1 (HDL1) when challenged with a high cholesterol, high saturated fat diet. These studies were conducted to determine the apoprotein composition and metabolic fate of HDL1 in the plasma. HDL1 particles containing apoA-I with and without apoE were detected. The majority of particles, however, contained apoA-I without any detectable apoE. To determine the metabolic fate of HDL1 in plasma, HDL1 labeled with iodinated apoA-I from animals with high levels of HDL1 and iodinated apoA-I-labeled autologous HDL were coinjected into both high and low HDL1 animals. The data for the decay of radioactivity in HDL1 and HDL were analyzed by multicompartment modelling. The radioactivity from HDL1 was cleared from the plasma either via direct removal (9.1 +/- 4.7% in low and 21.7 +/- 8.3% in high HDL1 animals) or via its conversion to HDL. A large proportion of radioactivity from HDL1 was rapidly transferred to HDL directly or metabolized via an intermediate compartment. Most of the radioactivity from apoE-poor HDL1, however, was transferred to HDL. Both high and low HDL1 animals catabolized HDL1 and HDL similarly. Low HDL1 animals transferred HDL1 radioactivity to HDL much faster. No detectable radioactivity from HDL was transferred to HDL1. Thus, HDL1 that accumulates in high HDL1 animals is mainly a precursor for HDL. Our hypothesis is that this accumulation of HDL1 is due to the slower cholesteryl ester transfer from HDL to lower density lipoproteins, thus affecting reverse cholesterol transport in high HDL1 baboons.