Hepatic lipase facilitates the selective uptake of cholesteryl esters fromremnant lipoproteins in apoE-deficient mice

We have investigated the role of hepatic lipase (HL) in remnant lipoprotein metabolism independent of lipolysis by using recombinant adenovirus to exp ress native and catalytically inactive HL (HL-145G) in apolipoprotein (apo) E-deficient mice characterized by increased plasma concentrations of apoB-4 8-containing remnants. In the absence of apoE, the mechanisms by which apoB -48-containing remnants are taken up by either low density lipoprotein (LDL )-receptor or LDC-receptor-related protein (LRP) remain unclear. Overexpres sion of either native or catalytically inactive HL in apoE-deficient mice l ed to similar reductions (P > 0.5) in the plasma concentrations of choleste rol (41% and 53%) and non high density lipoprotein (HDL)-cholesterol (41% a nd 56%) indicating that even in the absence of lipolysis, HL can partially compensate for the absence of apoE in this animal model, Although the clear ance of [H-3]cholesteryl ether from VLDL was significantly increased (appro ximately 2-fold; P < 0.02) in mice expressing native or inactive HL compare d to luciferase controls, the fractional catabolic rates (FCR) of [I-125-la beled] apoB- very low density lipoprotein (VLDL) in all three groups of mic e were similar (P > 0.4, all) indicating selective cholesterol uptake. Hepa tic uptake of [3H]cholesteryl ether from VLDL was greater in mice expressin g either native HL (87%) or inactive HL-145G (72%) compared to luciferase c ontrols (56%), Our combined findings are consistent with a role for HL in m ediating the selective uptake of cholesterol from remnant lipoproteins in a poE-deficient mice, independent of lipolysis. These studies support the con cept that hepatic lipase (HL) may serve as a ligand that mediates the inter action between remnant lipoproteins and cell surface receptors and/or prote oglycans, We hypothesize that one of these pathways may involve the interac tion of HL with cell surface receptors, such as scavenger receptor (SR)-BI, that mediate the selective uptake of cholesteryl esters.