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Hepatic uptake of chylomicron remnants in WHHL rabbits: a mechanism genetically distinct from the low density lipoprotein receptor.

Kita, T, Goldstein, J L, Brown, M S, Watanabe, Y, Hornick, C A, Havel, R J·1982·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.79.11.3623
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Abstract

Homozygous Watanabe hereditary hyperlipidemic (WHHL) rabbits have a near-complete deficiency of low density lipoprotein (LDL) receptors in liver and other tissues. As a result, these rabbits clear LDL from plasma at an abnormally slow rate. In the current studies we show that WHHL rabbits clear chylomicrons from plasma at a normal rate. Chylomicrons are cleared by a two-step process: (i) hydrolysis of triglycerides in extrahepatic tissues to yield cholesteryl ester-rich remnant particles and (ii) rapid uptake of the remnants by liver. Normal and WHHL rabbits were given intravenous injections of rat chylomicrons labeled either in the lipid portion with [3H]cholesterol and [14C]palmitate or in the protein portion with [125]iodine. All radiolabeled components were removed from plasma at comparable rates in normal and WHHL rabbits. Comparable amounts of radioactivity accumulated in livers of animals from both genotypes. In vitro assays showed that liver membranes from WHHL rabbits were markedly deficient in the binding of 125I-labeled chylomicron remnants as well as 125I-labeled LDL, implying that chylomicron remnants can bind to the hepatic LDL receptor. We conclude that the rabbit liver normally has at least two genetically distinct lipoprotein uptake mechanisms, both of which recognize chylomicron remnants: (i) the LDL receptor and (ii) a specific chylomicron remnant uptake mechanism that is not measured adequately by current in vitro membrane binding assays. WHHL rabbits possess a normal chylomicron remnant uptake mechanism that allows them to clear chylomicrons from plasma at a rapid rate despite their genetic deficiency of LDL receptors.

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Research works printed but not linked: 22

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Metadata

Authors
Kita, T., Goldstein, J. L., Brown, M. S., Watanabe, Y., Hornick, C. A., & Havel, R. J.
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
1982-06
Volume
79
Issue
11
Pages
3623-3627
ISSN
  • 0027-8424
  • 1091-6490
DOI
10.1073/pnas.79.11.3623
Cited by
167
References
0
Language
en

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