Differential suppression of lymphocyte cholesterol synthesis by low density lipoprotein and erythrocyte insulin receptors in normolipidemic subjects

Abstract

The rates of cholesterol synthesis from acetate were studied in freshly isolated peripheral blood lymphocytes in 41 age- and sex-matched subjects with essentially normal serum lipid profiles. Insulin binding to erythrocytes obtained from the same blood samples was also studied simultaneously. From the data on lymphocyte cholesterol synthesis in the absence or presence of low density lipoprotein in the medium, an index, LDL 50, was calculated for each subject. This is the concentration of LDL cholesterol (nmol/ml) in the medium necessary to reduce cholesterol synthesis to 50% of that in the absence of LDL. On the basis of LDL 50, the subjects could be segregated into three distinct groups, I, II, and III, with LDL 50 of 6.5, 23.3, and 77.0 nmol/ml, respectively. This grouping was independent of the serum lipid profiles, age or sex. Insulin binding studies showed that the amount of insulin specifically bound and the number of insulin receptors per cell were inversely correlated with LDL 50. LDL 50 was also determined for 4 subjects with clinically manifested consequences of familial hypercholesterolemia. The LDL 50 values for these individuals corresponded to values obtained for subjects in group III. The number of insulin receptors and the amount of insulin bound in these patients were correspondingly low. These results suggest that LDL 50 may be useful in discerning abnormal cellular cholesterol metabolism in subjects with or without accompanying hyperlipidemias.