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

We have investigated the role of hepatic lipase (HL) in remnant lipoprotein metabolism independent of lip- olysis by using recombinant adenovirus to express native and catalytically inactive HL (HL-145G) in apolipoprotein (apo)E-deficient mice characterized by increased plasma concentrations of apoB-48-containing remnants. In the absence of apoE, the mechanisms by which apoB-48-con- taining remnants are taken up by either low density lipopro- tein (LDL)-receptor or LDL-receptor-related protein (LRP) remain unclear. Overexpression of either native or catalyti- cally inactive HL in apoE-deficient mice led to similar re- ductions ( P. 0.5) in the plasma concentrations of choles- terol (41% and 53%) and non high density lipoprotein (HDL)-cholesterol (41% and 56%) indicating that even in the absence of lipolysis, HL can partially compensate for the absence of apoE in this animal model. Although the clearance of ( 3 H)cholesteryl ether from VLDL was signifi- cantly increased (approximately 2-fold; P , 0.02) in mice expressing native or inactive HL compared to luciferase controls, the fractional catabolic rates (FCR) of ( 125 I-labeled) apoB- very low density lipoprotein (VLDL) in all three groups of mice were similar ( P. 0.4, all) indicating selec- tive cholesterol uptake. Hepatic uptake of ( 3 H)cholesteryl ether from VLDL was greater in mice expressing either na- tive HL (87%) or inactive HL-145G (72%) compared to lu- ciferase controls (56%). Our combined findings are consis- tent with a role for HL in mediating the selective uptake of cholesterol from remnant lipoproteins in apoE-deficient mice, independent of lipolysis. These studies support the concept that hepatic lipase (HL) may serve as a ligand that mediates the interaction between remnant lipoproteins and cell surface receptors and/or proteoglycans. We hypothe- size that one of these pathways may involve the interaction of HL with cell surface receptors, such as scavenger recep- tor (SR)-BI, that mediate the selective uptake of cholesteryl esters.— Amar, M. J. A., K. A. Dugi, C. C. Haudenschild, R. D. Shamburek, B. Foger, M. Chase, A. Bensadoun, R. F. Hoyt, Jr., H. B. Brewer, Jr., and S. Santamarina-Fojo. Hepatic lipase facilitates the selective uptake of cholesteryl esters from remnant lipoproteins in apoE-deficient mice. J. Lipid Res. 1998. 39: 2436-2442.