Regulation of low-density-lipoprotein metabolism in the rat.

The mechanism of regulation of plasma low-density-lipoprotein (LDL) metabolism in the rat was studied under a number of experimental conditions. LDL clearance and uptake in the liver was measured after intravenous pulse injection of [14C]sucrose-labelled LDL alone or in combination with reductively methylated [3H]sucrose-labelled LDL. Hyperthyroid rats showed a significant increase in fractional catabolic rate (FCR) and the proportion of LDL degraded in the liver, whereas the synthetic rate of LDL increased by 50%. Receptor-mediated clearance increased 2-fold. Hypothyroid rats showed a significant increase in LDL concentration. The FCR and proportion of LDL degraded in the liver were decreased significantly. Receptor-mediated clearance was also reduced. Cholesterol feeding increased chylomicron, very-low-density-and intermediate-density-lipoprotein cholesterol concentrations, but there was no change in the LDL concentration, FCR or the synthetic rate of LDL. Cholestyramine feeding did not induce changes in the kinetic parameters. These results indicate that, in the rat, the hepatic LDL-receptor pathway is under hormonal control, whereas cholesterol and cholestyramine feeding have no demonstrated effect on LDL metabolism.