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. Sparks

University of Ottawa Heart Institute, Ottawa, Ontario K1Y 4W7

Corresponding Author: 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 apolipoproteinA-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. HDL2 have a greater capacity to remove HL from the cell surface and intracellular compartments as compared to the smaller HDL particles. The different HDL subclasses also uniquely affect the activity of the enzyme. HDL2 stimulates HL mediated hydrolysis of VLDL-TG, 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. The study suggests that high HDL2 levels are positively related to efficient TG hydrolysis by their ability to enhance the liberation of HL into the plasma compartment and by a direct stimulation of VLDL-TG hydrolysis.

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