Hepatic lipase promotes the selective uptake of high density lipoprotein-cholesteryl esters via the scavenger receptor B1

Hepatic lipase (HL) plays a major role in high-density lipoprotein (HDL) me tabolism both as a lipolytic enzyme and as a ligand. To investigate whether HL enhances the uptake of HDL-cholesteryl ester (CE) via the newly describ ed scavenger receptor BI (SR-BI), we measured the effects of expressing HL and SR-BI on HDL-cell association as well as uptake of I-125-labeled apoA-I and [H-3]CE-HDL, by embryonal kidney 293 cells. As expected, HDL cell asso ciation and CE selective uptake were increased in SR-BI transfected cells b y 2- and 4-fold, respectively, compared to controls (P < 0.001). Cells tran sfected with HL alone or in combination with SR-BI expressed similar amount s of HL, 20% of which was bound to cell surface proteoglycans, HL alone inc reased HDL cell association by 2-fold but had no effect on HDL-CE uptake in 293 cells, However, in cells expressing SR-BI, HL further enhanced the sel ective uptake of CE from HDL by 3-fold (P < 0.001). To determine whether th e lipolytic and/or ligand function of HL are required in this process, we g enerated a catalytically inactive form of HL (HL-145G). Cells co-transfecte d with HL-145G and SR-BI increased their HDL cell association and HDL-CE se lective uptake by 1.4-fold compared to cells expressing SR-BI only (P < 0.0 3). Heparin abolished the effect of HH-145G on SR-BI-mediated HDL-CE select ive uptake. Thus, the enhanced uptake of HDL-CE by HL is mediated by both i ts ligand role, which requires interaction with proteoglycans, and by Lipol ysis with subsequent HDL particle remodeling. These results establish HL as a major modulator of SR-BI mediated selective uptake of HDL-CE.