Impaired receptor-mediated catabolism of low density lipoproteins in fasted rabbits

Plasma cholesterol levels of New Zealand white rabbits, fasted for 9 days, increased 4-fold owing to elevated levels of low density lipoproteins and intermediate density lipoproteins. Estimates of the turnover of radioiodinated low density lipoproteins and methyl-low density lipoproteins using the Matthews model showed that clearance of low density lipoprotein by receptor-dependent pathways was reduced by 80%. Receptor-independent removal of low density lipoprotein was unchanged. The absolute catabolic rate of low density lipoprotein was not affected by fasting. EDTA-sensitive binding of 125I-labeled low density lipoproteins was selectively lost from liver membranes isolated from fasted rabbits. These results are consistent with the hypothesis that the hypercholesterolemia of fasted rabbits is the result of down-regulation of the hepatic low density lipoprotein receptor.