Rates of receptor-dependent and -independent low density lipoprotein uptake in the hamster

By using a constant infusion technique in the hamster, rates of uptake of [14C]sucrose-labeled hamster low density lipoprotein (hamLDL) and methylated hamster LDL (MehamLDL) were directly measured in 15 tissues. From these measurements the magnitude of LDL receptor-dependent and receptor-independent lipoprotein transport was calculated. The whole-animal clearance of hamLDL equaled 547 microliters/hr per 100 g of body weight. LDL clearance per g of tissue was highest in the liver (114 microliters/hr per g), ovary (43), spleen (36), adrenal gland (29), and intestine (24) and was lowest in fat (0.75), brain (0.35), and muscle (0.26). When adjusted for organ weight, the sum of the absolute clearance rates in all of the tissues examined equaled the rate of whole-animal LDL turnover. Liver accounted for 73%, and the jejunum and ileum combined accounted for 7% of whole-animal clearance. The 12 other tissues each accounted for only a minor portion of LDL clearance. Rates of uptake of Me-hamLDL were much less in many tissues and accounted for only 6-12% of the uptake of LDL in the liver, ovary, adrenal gland, lung, and kidney. However, this receptor-independent uptake was quantitatively more important in the intestine (44%) and spleen (72%) and accounted for essentially all LDL uptake in organs such as muscle, skin, and brain. Thus, in the hamster, most LDL is taken up and degraded by the liver. This uptake process is greater than 90% mediated by the LDL receptor and manifests saturation kinetics. Finally, cholestyramine feeding increases receptor-mediated LDL transport in the liver but in no other tissue studied.