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Journal of Lipid Research, Vol. 44, 733-741, April 2003
Copyright © 2003 by Lipid Research, Inc.

HDL regulates the displacement of hepatic lipase from cell surface proteoglycans and the hydrolysis of VLDL triacylglycerol

Tanya A. Ramsamy, Jonathan Boucher, Robert J. Brown, Zemin Yao and Daniel L. Sparks¹

Lipoprotein and Atherosclerosis Research Group and the Departments of Pathology & Laboratory Medicine and Biochemistry, Microbiology & Immunology, University of Ottawa Heart Institute, Ottawa, ON, Canada

¹ To whom correspondence should be addressed. e-mail: dsparks{at}ottawaheart.ca

We have previously shown that hepatic lipase (HL) is inactive when bound to purified heparan sulfate proteoglycans and can be liberated by HDL and apolipoprotein A-I (apoA-I), but not by LDL or VLDL. In this study, we show that HDL is also able to displace HL directly from the surface of the hepatoma cell line, HepG2, and Chinese hamster ovary cells stably overexpressing human HL. ApoA-I is more efficient at displacing cell surface HL than is HDL, and different HDL classes vary in their ability to displace HL from the cell surface. HDL₂s have a greater capacity to remove HL from the cell surface and intracellular compartments, as compared with the smaller HDL particles. The different HDL subclasses also uniquely affect the activity of the enzyme. HDL₂ stimulates HL-mediated hydrolysis of VLDL-triacylglycerol, while HDL₃ is inhibitory. Inhibition of VLDL hydrolysis appears to result from a decreased interlipoprotein shuttling of HL between VLDL and the smaller, more dense HDL particles.

This study suggests that high HDL₂ levels are positively related to efficient triacylglycerol hydrolysis by their ability to enhance the liberation of HL into the plasma compartment and by a direct stimulation of VLDL-triacylglycerol hydrolysis.

Abbreviations: CHO-hHL, Chinese hamster ovary cell line stably overexpressing human hepatic lipase; ECM, extracellular matrix; EMEM, Eagle's minimal essential medium; FAF-BSA, essentially fatty acid-free BSA; HL, hepatic lipase; HRP, horseradish peroxidase; HSPG, heparan sulfate proteoglycan; [³H]TG, [³H]triolein; MAb, monoclonal antibody; pen/strep, penicillin/streptomycin; POPC, palmitoyl-2-oleoyl-phosphatidylcholine; rHDL, reconstituted HDL

Supplementary key words heparan sulfate proteoglycans • apolipoprotein A-I • lipolysis

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