retinol-palmitate and Hyperlipoproteinemias

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

We have studied the large nonconsanguineous pedigree of a proband with Type I hyperlipoproteinemia (HL) and lipoprotein lipase (LPL) deficiency. Within the nuclear family, the mother and two of the proband's five siblings had fasting hypertriglyceridemia or low-normal tissue adipose LPL activities or both. Retention of lipoprotein retinyl esters after vitamin A feeding was present only in the propositus. The maternal side of the extended pedigree contained individuals with Types IIA, IV, and V hyperlipoproteinemia, findings most consistent with autosomal dominant multiple lipoprotein-type hyperlipidemia (familial combined hyperlipidemia). This family and previously reported pedigrees of Type I HL probands have demonstrated phenotypic heterogeneity. Without specific genetic markers, homozygous LPL deficiency and complex multiple-gene mechanisms cannot be distinguished unambiguously. Parental hyperlipidemia in nuclear pedigrees of Type I HL probands should not be equated with heterozygous LPL deficiency in the absence of extended pedigree data or more informative markers. The possibility that the complex inheritance of two different genetic defects in lipoprotein transport can produce the Type I HL phenotype must be considered.

Topics: Adipose Tissue; Adolescent; Adult; Aged; Child; Diterpenes; Female; Humans; Hyperlipoproteinemia Type I; Hyperlipoproteinemias; Lipids; Lipoprotein Lipase; Male; Middle Aged; Pedigree; Phenotype; Retinyl Esters; Triglycerides; Vitamin A