Saturation and suppression of hepatic lipoprotein receptors: a mechanism for the hypercholesterolemia of cholesterol-fed rabbits.

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Abstract
Cholesterol-fed rabbits develop a marked increase in plasma cholesterol levels. Most of the excess plasma cholesterol is contained in .beta.-migrating very low density lipoprotein (.beta.-VLDL), a cholesterol-rich particle that contains apoproteins B and E. When 125I-labeled .beta.-VLDL from cholesterol-fed rabbits was injected i.v. into normal rabbits, the lipoprotein was cleared rapidly from plasma 80% of the radioactivity appearing in the liver within 4 min. In vitro binding assays showed that this uptake was due to the presence on liver membranes of a high-affinity, low-capacity binding site that resembles the low density lipoprotein receptor previously characterized on extrahepatic tissues. When the 125I-labeled .beta.-VLDL was injected into cholesterol-fed rabbits hepatic uptake was reduced by > 95% and the lipoprotein remained in the plasma. This defective uptake in cholesterol-fed rabbits was due to 2 factors: saturation of the lipoprotein receptors by the high concentration of endogenous plasma .beta.-VLDL; a 60% reduction in the number of hepatic receptors after cholesterol feeding. Of the 2 factors saturation of receptors was quantitatively more important. As a result of the saturation and suppression of receptors, the hepatic removal of .beta.-VLDL in the cholesterol-fed rabbit evidently fails to increase commensurate with the diet-induced increase in .beta.-VLDL synthesis and profound hypercholesterolemia ensues.

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