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Journal of Lipid Research, Vol. 45, 1683-1693, September 2004
Copyright © 2004 by American Society for Biochemistry and Molecular Biology

Role of cholesteryl ester transfer protein in selective uptake of high density lipoprotein cholesteryl esters by adipocytes

Gerard Vassiliou¹ and Ruth McPherson¹

Lipoprotein and Atherosclerosis Group, University of Ottawa Heart Institute, Ottawa, Ontario K1Y 4E9, Canada

¹ To whom correspondence should be addressed. e-mail: gvass{at}ottawaheart.ca (G. V.); rmcpherson{at}ottawaheart.ca (R. M.)

Previous reports attributed cholesteryl ester transfer protein (CETP)-mediated HDL cholesteryl ester (CE) selective uptake to the CETP-mediated transfer of CE from HDL to newly secreted apolipoprotein B-containing lipoproteins, which are then internalized by the LDL receptor (LDL-R). CETP has also been implicated in the remodeling of HDL, which renders it a better substrate for selective uptake by scavenger receptor class B type I (SR-BI). However, CETP-mediated selective uptake of HDL₃-derived CE was not diminished in LDL-R null adipocytes, SR-BI null adipocytes, or in the presence of the receptor-associated protein. We found that monensin treatment or energy depletion of the SW872 liposarcoma cells with 2-deoxyglucose and NaN₃ had no effect on CETP-mediated selective uptake, demonstrating that endocytosis is not required. This is supported by data indicating that CETP transfers CE into a compartment from which it can be extracted by unlabeled HDL. CETP could also mediate the selective uptake of HDL₃-derived triacylglycerol (TG) and phospholipid (PL). The CETP-specific kinetics for TG and CE uptake were similar, and both reached saturation at 5 µg/ml HDL. In contrast, CETP-specific PL uptake did not attain saturation at 5 µg/ml HDL and was 6-fold greater than the uptake of CE.

We propose two possible mechanisms to account for the role of CETP in selective uptake.

Abbreviations: ₂M, ₂-macroglobulin; apoB, apolipoprotein B; CE, cholesteryl ester; CETP, cholesteryl ester transfer protein; LDL-R, LDL receptor; LRP, LDL receptor-related protein; MX, 4-methyl umbelliferyl-ß-D-xyloside; PL, phospholipid; RAP, receptor-associated protein; SR-BI, scavenger receptor class B type I; TG, triacylglycerol; Tmax, maximal transport rate

Supplementary key words energy depletion • monensin • scavenger receptor class B type I • SW872 liposarcoma cells

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