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

P. T. Kovanen, M. S. Brown, S. K. Basu, D. W. Bilheimer, J. L. Goldstein

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Abstract

Cholesterol-fed rabbits develop a marked in crease 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 intravenously 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 more than 95% and the lipoprotein remained in the plasma. This defective uptake in cholesterol-fed rabbits was due to two factors: (i) saturation of the lipoprotein receptors by the high concentration of endogenous plasma beta-VLDL and (ii) a 60% reduction in the number of hepatic receptors after cholesterol feeding. Of the two factors, saturation of receptors was quantitatively more important. We suggest that, as a result of the saturation and suppression of receptors, the hepatic removal of beta-VLDL in the cholesterol-fed rabbit fails to increase commensurate with the diet-induced increase in beta-VLDL synthesis and profound hypercholesterolemia ensues.

Original languageEnglish (US)
Pages (from-to)1396-1400
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume78
Issue number3
Publication statusPublished - Mar 1981

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ASJC Scopus subject areas

  • General
  • Genetics

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