HEPATIC-UPTAKE AND PROCESSING OF CHOLESTEROL AND CHOLESTERYL ESTER FROM CHYLOMICRON REMNANTS - AN INVIVO STUDY IN THE RAT

The metabolic fate of cholesterol in chylomicron remnants was studied after intravenous infusion into biliary drained rats. The remnants were radiolabelled with [H-3]cholesterol in vivo, so that radioactivity was incorporated into both the unesterified (27% of label) and the esterified (73% of label) cholesterol fractions, or with C-14-labelled unesterified cholesterol after exchange in vitro. Blood and bile samples were collected at intervals for 180 min, after which the animals were killed for analysis. The total amount of radioactivity found in the liver (46%) and bile (4.5%) after infusion of [H-3] remnants was higher than that found when the label was C-14 (33 and 2.7%, respectively). Radioactivity from C-14-labelled unesterified cholesterol was cleared more rapidly from the blood, but the distribution of the label between the lipoprotein fractions VLDL + LDL, HDL2 and HDL3 at the end of the experiment was similar to that found when total [H-3]cholesterol was used. In experiments with both types of label, approximately 94% of the total radioactivity secreted into bile was associated with the bile acid, with only about 6% in biliary unesterified cholesterol, and these proportions did not change during 180 min. When the chylomicron remnants were labelled with total [H-3]cholesterol the specific radioactivity of the bile acid, taurochenodeoxycholic acid, in the bile was approximately twice that observed when the label was unesterified [C-14]cholesterol. The specific radioactivity of unesterified biliary cholesterol was very low in the latter case, but higher and more comparable to that of taurochenodeoxycholic acid in the former. Thus, the metabolic fate of chylomicron remnant cholesterol differs, depending on whether it is in the esterified or unesterified form, suggesting that hepatic cholesterol originating from the two fractions may mix to a different extent with the various intracellular pools. In addition, the experiments with C-14 indicate that the behaviour of chylomicron remnant unesterified cholesterol resembles that exhibited by cholesterol in HDL more than that carried in VLDL or LDL.