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The Journal of Lipid Research, Vol. 39, 1335-1348, July 1998
Copyright © 1998 by Lipid Research, Inc.

Original Article

Lipoprotein lipase mediates an increase in the selective uptake of high density lipoprotein-associated cholesteryl esters by hepatic cells in culture

Correspondence to: Franz Rinninger.

In this study the effect of lipoprotein lipase (LPL) on the selective uptake of high density lipoprotein (HDL) cholesteryl esters (CE) by hepatic cells was investigated. Human HDL₃ (d 1.125–1.21 g/ml) was radiolabeled with ¹²⁵I in the protein moiety and with ³H in the CE moiety. LPL was prepared from bovine milk. Human hepatocytes in primary culture and human Hep3B hepatoma cells were incubated in medium containing doubly radiolabeled HDL₃ with or without LPL. Without LPL, apparent HDL₃ particle uptake according to the lipid tracer (³H) was in excess of that due to the protein label (¹²⁵I) indicating selective CE uptake from HDL₃. Addition of LPL increased selective CE uptake up to 7-fold. This stimulation of HDL₃ selective CE uptake was independent of the lipolytic activity of LPL as suggested by several experimental approaches. Cell surface heparan sulfate proteoglycan deficiency decreased the LPL-mediated increase in selective CE uptake suggesting an important role for these molecules. In low density lipoprotein (LDL) receptor- or LDL receptor-related protein-(LRP)-deficient cells, LPL increased selective CE uptake as it did in normal cells yielding no evidence that these receptors play a role in the LPL effect on selective CE uptake.

In summary, lipoprotein lipase increases the selective uptake of high density lipoprotein-associated cholesteryl ester by hepatic cells in culture. This effect is dependent on cell surface heparan sulfate proteoglycans but independent of lipolysis and of endocytosis mediated by low density lipoprotein receptor-related or low density lipoprotein receptors.—Rinninger, F., T. Kaiser, W. A. Mann, N. Meyer, H. Greten, and U. Beisiegel. Lipoprotein lipase mediates an increase in the selective uptake of high density lipoprotein-associated cholesteryl esters by hepatic cells in culture. J. Lipid Res. 1998. 39: 1335–1348.

Supplementary key words: HDL, cholesteryl ester, selective uptake, lipoprotein lipase, liver, reverse cholesterol transport

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