THE LOW-DENSITY-LIPOPROTEIN RECEPTOR AND CHOLESTEROL-SYNTHESIS ARE AFFECTED DIFFERENTLY BY DIETARY-CHOLESTEROL IN THE RAT

In the hamster and the rabbit, the low-density lipoprotein (LDL) recep tor and cholesterol synthesis are coordinately downregulated by dietar y cholesterol. In the rat, cholesterol synthesis is downregulated but LDL kinetic studies suggest that the LDL receptor is not. The aim of t his study was to determine the effect of dietary cholesterol on the ex pression of the hepatic LDL receptor in the rat. Young (2 months) hood ed and albino Wistar rats and older (9 months) Sprague-Dawley rats wer e used because of their reported different propensities to develop hyp ercholesterolaemia when fed cholesterol. Hepatic LDL receptor activity was measured using a dot blot assay with LDL-gold and LDL receptor ma ss was measured using an electroblot assay with a polyclonal antibody. Dietary cholesterol had no effect on the plasma cholesterol concentra tion in both strains of young Wistar rats but increased it in the olde r Sprague-Dawley rats. Cholesterol synthesis as measured with (H2O)-H- 3 or as indicated by 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) r eductase activity or the ratio of plasma lathosterol to cholesterol wa s effectively downregulated by dietary cholesterol (1% w/w) in all thr ee strains. In contrast, dietary cholesterol increased both hepatic LD L receptor activity and mass in the young Wistar rats and had no effec t on either receptor activity or mass in the older Sprague-Dawley rats . Increases in receptor activity occurred despite increases in hepatic cholesterol especially when cholic acid was added to the cholesterol diet. The effect was systemic because CL 277 082, an inhibitor of inte stinal cholesterol absorption, prevented the increase in LDL receptor activity. The LDL receptor and cholesterol synthesis are therefore aff ected differently by dietary cholesterol in the rat.