Lipoprotein Metabolism in Normal and WHHL-Rabbit

Abstract

We studied the metabolic behavior of exogenous and endogenous cholesterol carrying lipoproteins in vivo.Normal and WHHL-rabbits were given intravenous injection of chylomicrons labeled either in the lipid portion with [3H] cholesterol or in the protein portion with [125I] iodine. All radiolabeled components were removed from plasma at comparable rates and the bulk of the radioactivity was found in the liver in both genotypes. It suggests that liverr has a specific chylomicron remnants receptor.Normal and WHHL-rabbits were given intravenous injection of 125I-LDL and VLDL. The FCR for LDL in WHHL-rabbit was about one third the normal rate. That could not account for 20-fold increase of LDL in this rabbit. When 125I-VLDL was injected to normal rabbit, it was converted to IDL and more than 90% of IDL was taken up by the liver rapidly. On the contrary, once VLDL was converted to IDL in WHHL-rabbit, it failed to enter the liver for catabolism, subsequently converted to LDL. These data suggest that endogenous lipoproteins require LDL receptor for their catabolism, and decreasing amounts of hepatic LDL receptors lead not only to impaired catabolism but to overproduction of LDL by the shunt mechanism.