Effects of Diet on Apoprotein E Levels and on the Apoprotein E Subspecies in Human Plasma Lipoproteins*

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Abstract
Type III hyperlipoproteinemia is characterized by a marked deficiency of the apoprotein E (ApoE)-3 subspecies of ApoE in very low density lipoproteins (VLDL). To assess whether the relative proportions in ApoE (and hence the ApoE-3 deficiency in type III) are constant in the face of dietary alterations, 7 type III subjects, 5 subjects with primary endogenous hypertriglyceridemia (type IV) and 6 normal controls before and after they ate a high carbohydrate diet were studied. Three type III subjects and 2 normal controls were studied before and 4 h after the ingestion of 150 g of a corn oil emulsion. Lipids were measured chemically on lipoprotein fractions isolated by ultracentrifugation and heparin-MnCl2 precipitation. ApoE levels in plasma and VLDL were measured by a RIA [radioimmunoassay] described in this communication, and the ApoE subspecies were quantified by isoelectric focusing. After 7 days of the carbohydrate diet, fasting triglyceride levels in VLDL [density (d) < 1.006] rose .apprx. 90% over basal levels and all lipoprotein lipid compositions were altered. ApoE levels in whole plasma remained relatively constant but ApoE rose in VLDL (d < 1.006) and fell in the d > 1.006 infranates. The relative proportions of the ApoE subspecies in VLDL (d < 1.006) and in VLDL subfractions (Sf 20-60, Sf 60-100, and Sf 100-400; isolated by density gradient ultracentrifugation) remained unchanged, i.e., ApoE-3 continued to be absent in patients with type III hyperlipidemia and the proportions of ApoE subspecies remained unchanged in the VLDL of normal controls and hypertriglyceridemic (type IV) subjects. Triglyceride levels rose by .apprx. 75% 4 h after the fat meal but ApoE-3 deficiency persisted in the Sf > 400 (chylomicron) fractions of type III subjects and the proportion of the ApoE subspecies in chylomicrons of normal controls remained unchanged. These data suggest that to the extent that the ApoE on VLDL and chylomicrons represented newly secreted ApoE the ApoE-3 deficiency in type III was already present in newly secreted apoproteins. The constancy of the ApoE patterns in normals and hypertriglyceridemic patients further suggests that the 2 dietary perturbations used in these studies do not alter the relative proportions of the various subspecies of ApoE.