Journal of Lipid Research, Vol 30, 1147-1159, Copyright © 1989 by Lipid Research, Inc.
Metabolism of larger high density lipoproteins accumulating in some families of baboons fed a high cholesterol and high saturated fat diet
RS Kushwaha, DM Foster, VN Murthy, KD Carey and HC McGill Jr
Department of Physiology and Medicine, Southwest Foundation for Biomedical Research, San Antonio, TX 78284.
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.