retinol-palmitate and Hyperlipoproteinemia-Type-IV

To study post-prandial lipoprotein metabolism in normolipidemic and hypertriglyceridemic subjects, a vitamin A fat loading test was used. This method specifically labels dietary fat particles with retinyl palmitate (RP). Following RP concentrations, metabolic behavior of chylomicrons and chylomicron remnants were studied. In normal subjects, post-prandial lipoproteins were present for more than 10 h. Total RP increased rapidly between 1 and 4 h, peaked at 6 h and declined rapidly between 6 and 10 h. The chylomicron and chylomicron remnant fractions behaved differently, showing precursor product relationship. The hypertriglyceridemic patients demonstrated a very severe defect in chylomicron clearance. This fraction was 2.8-fold higher than in normal subjects, which was 7,260 vs. 2,600 micrograms/l, respectively. The large magnitude and long duration of post-prandial lipemia in normal and hypertriglyceridemic patients support the hypothesis that these atherogenic particles may play a role in the development of coronary heart disease.

Topics: Adult; Aged; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Chromatography, High Pressure Liquid; Chylomicrons; Dietary Fats; Diterpenes; Evaluation Studies as Topic; Humans; Hyperlipoproteinemia Type IV; Metabolic Clearance Rate; Middle Aged; Retinyl Esters; Time Factors; Triglycerides; Vitamin A

The kinetics of chylomicron metabolism have been studied by measuring retinyl palmitate in chylomicrons and their remnants for 10-12 hr following oral administration of vitamin A and Lipomul in three groups of adult male subjects: A) normal plasma triglyceride levels (n = 7); B) endogenous hypertriglyceridemia (n = 12); C) apolipoprotein E (apoE) phenotype E2/2, with Type 3 hyperlipoproteinemia (n = 4) or normal plasma lipids (n = 1). A multicompartmental model was developed using SAAM 27 to characterize the appearance, intravascular metabolism, and clearance from the plasma of retinyl palmitate-labeled dietary lipoproteins. The half-times for retinyl palmitate clearance from the chylomicron remnant fraction (T1/2 REMNANT) were 14.1 +/- 9.7 min in Group A; they were prolonged in Group B (50.7 +/- 20.8 min) and were extremely prolonged for Type 3 subjects in Group C (611.9 +/- 419.9 min). One subject with the apoE 2/2 phenotype and normal plasma triglycerides had a T1/2 REMNANT of 66.8 min. T1/2 REMNANT was highly correlated with fasting plasma triglycerides in Group A and B (r = 0.77, slope = 0.15), and in Group C (r = 0.97, slope = 0.85). These results support the interpretation that delayed chylomicron remnant clearance in subjects with endogenous hypertriglyceridemia may be largely secondary to overproduction of VLDL particles, whose remnants compete with chylomicron remnants for removal by the liver via apoE receptor-mediated endocytosis. The subjects with apoE 2/2 have an additional defect in the removal of chylomicron remnants presumably due to the structural abnormality in their apoE.

Topics: Adult; Aged; Chylomicrons; Diterpenes; Half-Life; Humans; Hyperlipoproteinemia Type III; Hyperlipoproteinemia Type IV; Hyperlipoproteinemias; Kinetics; Male; Middle Aged; Retinyl Esters; Vitamin A