Metabolic fate of low density lipoprotein and high density lipoprotein labeled with an ether analogue of cholesteryl ester

Summary

Low density lipoprotein (LDL) metabolism by human skin fibroblasts was studied using LDL labeled with a nonhydrolyzable cholesteryl ether analogue,³H-cholesteryl linoleyl ether (CLE). The³H-CLE-LDL was taken up by the apo-B, E receptor mediated endocytosis similar to¹²⁵I-labeled LDL. This was shown by saturation kinetics of uptake with respect to³H-CLE-LDL concentration and very low uptake of³H-CLE-LDL by receptor negative cell strains. When injected into rats,³H-CLE-LDL and¹⁴C- cholesteryl ester (CE)-LDL were cleared at equal rates and about 30% of the injected LDL was recovered in the liver. Treatment with ethinyl estradiol resulted in a three-fold increase in³H-CLE-LDL uptake by the liver. The liver is also the major site of uptake of³H-CLE-high density lipoprotein (HDL) (40%–45% of the injected dose) but its uptake by the liver increased only by 20% with estradiol treatment. As³H-CLE-HDL was cleared from the circulation at a somewhat faster rate than¹²⁵I-HDL it appeared that some dissociation in the tissue uptake of the protein and CE moieties occurs.