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Journal of Lipid Research, Vol. 45, 2088-2095, November 2004
Copyright © 2004 by American Society for Biochemistry and Molecular Biology

Scavenger receptor class B type I is solely responsible for the selective uptake of cholesteryl esters from HDL by the liver and the adrenals in mice

Ruud Out¹, Menno Hoekstra¹, John A. A. Spijkers, Johan K. Kruijt, Miranda van Eck, Ingrid S. T. Bos, Jaap Twisk and Theo J. C. Van Berkel²

Leiden/Amsterdam Center for Drug Research, Division of Biopharmaceutics, Gorlaeus Laboratories, Leiden University, 2300 RA Leiden, The Netherlands

² To whom correspondence should be addressed. e-mail: t.berkel{at}lacdr.leidenuniv.nl

Scavenger receptor class B type I (SR-BI) has been identified as a functional HDL binding protein that can mediate the selective uptake of cholesteryl ester (CE) from HDL. To quantify the in vivo role of SR-BI in the process of selective uptake, HDL was labeled with cholesteryl ether ([³H] CEt-HDL) and ¹²⁵I-tyramine cellobiose ([¹²⁵I]TC-HDL) and injected into SR-BI knockout (KO) and wild-type (WT) mice. In SR-BI KO mice, the clearance of HDL-CE from the blood circulation was greatly diminished (0.043 ± 0.004 pools/h for SR-BI KO mice vs. 0.106 ± 0.004 pools/h for WT mice), while liver and adrenal uptake were greatly reduced. Utilization of double-labeled HDL ([³H]CEt and [¹²⁵I]TC) indicated the total absence in vivo of the selective decay and liver uptake of CE from HDL in SR-BI KO mice. Parenchymal cells isolated from SR-BI KO mice showed similar association values for [³H]CEt and [¹²⁵I]TC in contrast to WT cells, indicating that in parenchymal liver cells SR-BI is the only molecule exerting selective CE uptake from HDL.

Thus, in vivo and in vitro, SR-BI is the sole molecule mediating the selective uptake of CE from HDL by the liver and the adrenals, making it the unique target to modulate reverse cholesterol transport.

Abbreviations: CE, cholesteryl ester; CEt, cholesteryl ether; FCR, fractional catabolic rate; ID, injected dose; KO, knockout; oxLDL, oxidized LDL; RCT, reverse cholesterol transport; SR-BI, scavenger receptor class B type I; TC, tyramine-cellobiose; WT, wild-type

Supplementary key words lipid metabolism • reverse cholesterol transport • scavenger receptor class B type I • high density lipoprotein • knockout mouse • liver cells

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