Fate of Cholesteryl Linoleyl Ether Injected Into Rats as Chylomicrons, Acetylated LDL and HDL

Abstract

During the past few years we have used cholesteryl linoleyl ether, a nonhydrolyzable analogue of cholesteryl ester, to study cellular uptake of lipoprotein cholesteryl ester in culture^1-3 and in the intact animal.^4-7 In experiments with low density lipoproteins which had been modified by acetylation, and thus targeted for uptake by non- parenchymal cells, the hepatic retention of a labeled ether analogue of triacylglycerol was encountered even several weeks after injection.^8-9 When chylomicrons labeled with [¹⁴C]cholesteryl linoleyl ether and retinyl [³H]hexadecyl ether were injected (Fig. 1), loss of both labeled compounds from the liver was encountered already 1 week after injection.¹⁰ The question was whether labeled cholesteryl ether disappears more quickly when injected as part of lipoprotein taken preferentially by hepatocytes and persists much longer in the liver when injected as a part of acetylated LDL, which is taken up preferentially by nonparenchymal cells.^11,12 Groups of rats were injected simultaneously with chylomicrons and acetylated low density lipoprotein labeled with [¹⁴C]- or [³H]cholesteryl linoleyl ether and the hepatic retention was monitored up to 70 days after injection. The results obtained provide evidence that cholesteryl linoleyl ether is retained in the liver for many weeks if it is injected as part of acetylated LDL (Fig. 2), and thus taken up mainly by nonparenchymal cells. ^{11, 12} A relatively slow but progressive elimination of the labeled cholesteryl linoleyl ether occurred when it had been injected bound to chylomicrons (Fig. 2), which were taken up and metabolized mainly by hepatocytes.