Catabolism of chylomicron remnants in normolipidemic subjects in relation to the apoprotein E phenotype

Abstract

The role of the various apolipoprotein E isoproteins in the removal of chylomicrons and their remnants from plasma was studied in 16 normolipidemic subjects with various apoE phenotypes: 5 homozygous for apoE-2, 6 heterozygous for apoE-2 (phenotype E3/2), and 5 without apoE-2 (phenotypes E3/3, E4/4, and E4/3). The subjects were given an oral fat load as cream (50 g/m2). Retinyl palmitate was added as a marker for chylomicrons and their remnants. Blood was sampled at regular time intervals for 8 hr. Remnant particles were isolated from the d less than 1.019 g/ml fraction by heparin-Sepharose chromatography (heparin-bound fraction) after removing the large chylomicrons by flotation at 7,8 X 10(5) g-min. All groups showed a rise in triglycerides in serum and in the chylomicron fraction between 3 and 6 hr to about twice the basal value, followed by a decrease to nearly fasting values. In the homozygous E-2 subjects, fasting lipids in the remnant fraction were increased. In all three groups the fat load did not induce a significant rise in the lipids of the remnant fraction. The homozygous E-2 group showed a strong continuing rise in the retinyl palmitate concentration in the chylomicron and remnant fractions up to 8 hr, whereas in the other groups its maximum was already reached at 5 hr at a much lower level. At 8 hr similar retinyl palmitate concentrations were found in both fractions in the heterozygous E-2 subjects compared to the non-E-2 subjects. These results indicate a delayed removal of chylomicrons and chylomicron remnants in normolipidemic homozygous E-2, but not in heterozygous E-2 subjects.