Hepatic uptake of chylomicron remnants in WHHL rabbits: a mechanism genetically distinct from the low density lipoprotein receptor - PubMed (original) (raw)
Hepatic uptake of chylomicron remnants in WHHL rabbits: a mechanism genetically distinct from the low density lipoprotein receptor
T Kita et al. Proc Natl Acad Sci U S A. 1982 Jun.
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.
Similar articles
- Chylomicron metabolism in normal, cholesterol-fed, and Watanabe heritable hyperlipidemic rabbits. Saturation of the sequestration step of the remnant clearance pathway.
Hussain MM, Innerarity TL, Brecht WJ, Mahley RW. Hussain MM, et al. J Biol Chem. 1995 Apr 14;270(15):8578-87. doi: 10.1074/jbc.270.15.8578. J Biol Chem. 1995. PMID: 7721759 - Defective plasma clearance of chylomicron-like lipid emulsions in Watanabe heritable hyperlipidemic rabbits.
Mamo JC, Bowler A, Elsegood CL, Redgrave TG. Mamo JC, et al. Biochim Biophys Acta. 1991 Feb 5;1081(3):241-5. doi: 10.1016/0005-2760(91)90277-o. Biochim Biophys Acta. 1991. PMID: 1998743 - Watanabe heritable hyperlipidemic rabbit. Animal model for familial hypercholesterolemia.
Havel RJ, Yamada N, Shames DM. Havel RJ, et al. Arteriosclerosis. 1989 Jan-Feb;9(1 Suppl):I33-8. Arteriosclerosis. 1989. PMID: 2643428 Review. - Chylomicron remnants: hepatic receptors and metabolism.
Havel RJ. Havel RJ. Curr Opin Lipidol. 1995 Oct;6(5):312-6. doi: 10.1097/00041433-199510000-00011. Curr Opin Lipidol. 1995. PMID: 8520854 Review.
Cited by
- Garcinia cambogia Extract Increased Hepatic Levels of Lipolysis-Stimulated Lipoprotein Receptor and Lipids in Mice on Normal Diet.
Hanse M, Akbar S, Layeghkhavidaki H, Yen FT. Hanse M, et al. Int J Mol Sci. 2023 Nov 14;24(22):16298. doi: 10.3390/ijms242216298. Int J Mol Sci. 2023. PMID: 38003494 Free PMC article. - EDEM3 Modulates Plasma Triglyceride Level through Its Regulation of LRP1 Expression.
Xu YX, Peloso GM, Nagai TH, Mizoguchi T, Deik A, Bullock K, Lin H, Musunuru K, Yang Q, Vasan RS, Gerszten RE, Clish CB, Rader D, Kathiresan S. Xu YX, et al. iScience. 2020 Apr 24;23(4):100973. doi: 10.1016/j.isci.2020.100973. Epub 2020 Mar 11. iScience. 2020. PMID: 32213464 Free PMC article. - News on the molecular regulation and function of hepatic low-density lipoprotein receptor and LDLR-related protein 1.
van de Sluis B, Wijers M, Herz J. van de Sluis B, et al. Curr Opin Lipidol. 2017 Jun;28(3):241-247. doi: 10.1097/MOL.0000000000000411. Curr Opin Lipidol. 2017. PMID: 28301372 Free PMC article. Review. - Hepatic remnant lipoprotein clearance by heparan sulfate proteoglycans and low-density lipoprotein receptors depend on dietary conditions in mice.
Foley EM, Gordts PLSM, Stanford KI, Gonzales JC, Lawrence R, Stoddard N, Esko JD. Foley EM, et al. Arterioscler Thromb Vasc Biol. 2013 Sep;33(9):2065-74. doi: 10.1161/ATVBAHA.113.301637. Epub 2013 Jul 11. Arterioscler Thromb Vasc Biol. 2013. PMID: 23846497 Free PMC article. - Shedding of syndecan-1 from human hepatocytes alters very low density lipoprotein clearance.
Deng Y, Foley EM, Gonzales JC, Gordts PL, Li Y, Esko JD. Deng Y, et al. Hepatology. 2012 Jan;55(1):277-86. doi: 10.1002/hep.24626. Epub 2011 Dec 6. Hepatology. 2012. PMID: 21898481 Free PMC article.
References
- Atherosclerosis. 1978 Nov;31(3):355-64 - PubMed
- Biochim Biophys Acta. 1979 May 25;573(2):255-65 - PubMed
- J Biol Chem. 1980 Mar 10;255(5):1804-7 - PubMed
- J Biol Chem. 1980 Jun 10;255(11):5475-80 - PubMed
- Proc Natl Acad Sci U S A. 1980 May;77(5):2465-9 - PubMed
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Research Materials