THE DIURNAL RHYTHMS OF CHOLESTEROL-METABOLISM AND PLASMA-CLEARANCE OFMODEL CHYLOMICRONS - COMPARISON OF NORMAL AND GENETICALLY HYPERCHOLESTEROLEMIC RATS (RICO)

Previous studies showed a slower clearance of cholesterol-labeled lymp h chylomicrons in genetically hypercholesterolemic rats (RICO) compare d with normocholesterolemic rats. In this study, we compared rates of lipolysis and remnant clearance in RICO versus control normocholestero lemic rats of the same strain (RAIF) or with control Wistar rats, by i njecting chylomicron-like lipid emulsions labeled with C-14-triolein t o trace lipolysis, and H-3-cholesteryl ester to trace remnant clearanc e. Our findings showed slower clearance of chylomicron remnants in RIC O compared with control RAIF or with control Wistar rats. During the l ight period, the clearance of lipids from chylomicron-like lipid emuls ions injected intravenously was significantly slower in RICO rats comp ared with normocholesterolemic control rats of the same strain, RAIF. Within the RICO group, clearance of emulsion triolein (TO) was faster during the dark period compared with the light period. In contrast, ho wever, the clearance of the emulsion remnants traced by cholesteryl ol eate (CO) was slower during the dark period. This behaviour was not fo und within the Wistar group, where the clearances of TO and CO were si milar in the light and dark period. Hepatic clearance of chylomicron r emnants is mediated primarily by the low density lipoprotein (LDL) rec eptor, the expression of which shows diurnal variation. In both Wistar and RICO rats, the expression of LDL receptors was highest during the dark period. The LDL receptors in hepatic microsomal membranes from R ICO rats migrated faster on SDS polyacrylamide gel electrophoresis whe n compared with normal Wistar and the RAIF. However in hepatic plasma membranes the LDL receptors from RICO and Wistar rats appeared identic al after immunoblotting. Furthermore the LDL receptors from RICO and W istar rats responded similarly to treatment with neuraminidase. An alt eration in post-translational processing of the LDL receptor could pos sibly account for the slower clearance of chylomicron remnants in the RICO. (C) 1998 Elsevier Science Inc. All rights reserved.