Tissue sites of catabolism of rat and human low density lipoproteins in rats

Abstract

We have determined the sites of degradation of low density lipoprotein in rats using covalently linked [14C] sucrose as tracer. On degradation, 14C is trapped intracellularly as a cumulative measure of the amount of protein catabolized by each tissue. [14C] Sucrose-labeled rat low density lipoprotein (d 1.02-1.05 g/ml) was cleared from the plasma at a rate (0.092 +/- 0.003 h-1) similar to that for 125I-labeled LDL (0.096 +/- 0.22 h-1). Tissues were examined for total 14C content 24 h after injection of 14C-labeled lipoprotein. At death, animals were perfused thoroughly to remove trapped plasma. Recovery of 14C in tissue was 100 +/- 23% of catabolized 14C-labeled lipoprotein (calculated from plasma decay kinetics). In three test tissues, leakage of 14C over 5 days was less than 10%/day; leakage from liver was 10%/day, predominantly into bile; 14C content of kidney increased slightly. Thus, 14C trapping was adequate. The 14C-labeled lipoprotein was catabolized 66.8 +/- 2.5% by liver. No other organ catabolized more than 8%. Liver, adrenal and ovary were the most active per unit wet weight, followed by spleen. Urinary excretion, in 24h, was 3% and biliary excretion was 7% of catabolized. Human low density lipoproteins were similarly examined with similar results; this similarity may be due to exchange of rat apolipoproteins onto human lipoprotein in the circulation.