Cholesterol metabolism in the genetically hypercholesterolemic (RICO) rat. II. A study of plasma lipoproteins and effect of dietary cholesterol

Abstract

The high plasma cholesterol concentration of the genetically hypercholesterolemic RICO rats fed a low cholesterol base diet (1.28 mg/ml) compared to that of SW rats (0.73 mg/ml) results from an increase in the cholesterol content of the d ⩾ 1.006 lipoproteins. Since the composition of each type of lipoprotein is similar in the two groups of rats, the RICO rat, therefore, is hyperlipoproteinemic with an increase in the number of lipoprotein particles, except VLDL and chylomicrons. Furthermore, the apolipoprotein E (apoE) content in the d ⩽ 1.063 lipoproteins is higher in RICO than in SW rats, while that of apoA-I in HDL is lower. In rats fed 0.5% cholesterol base diet, cholesterolemia doubles in the two groups (SW CH, 1.32 ± 0.10 mg/ ml; RICO CH, 2.10 ± 0.09 mg/ ml). This hypercholesterolemia is due to an increased cholesterol content in VLDL and chylomicrons. These lipoproteins carry 60% (in SW CH) and 45% (in RICO CH) of the plasma cholesterol and are cholesterol-enriched compared with the lipoproteins observed in rats fed the base diet. In RICO CH, 24% of the plasma cholesterol is found in apoE-rich LDL 2 (1.040 ⩽ d ⩽ 1.063), whereas in SW CH, this fraction contains only 11% of the plasma cholesterol. Finally, as before with the base diet, RICO CH shows an apoE enrichment of the d ⩽ 1.063 lipoproteins and an apoA-I depletion of HDL compared to SW CH. These data suggest that hypercholesterolemia of the RICO rats results from a modification in the turnover of apoE-containing lipoproteins.