title: Hepatic lipase facilitates the selective uptake of cholesteryl esters from remnant lipoproteins in apoE-deficient mice.
abstract: We have investigated the role of hepatic lipase (HL) in remnant lipoprotein metabolism independent of lipolysis 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-containing remnants are taken up by either low density lipoprotein (LDL)-receptor or LDL-receptor-related protein (LRP) remain unclear. Overexpression of either native or catalytically inactive HL in apoE-deficient mice led to similar reductions (P > 0.5) in the plasma concentrations of cholesterol (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 [3H]cholesteryl ether from VLDL was significantly increased (approximately 2-fold; P < 0. 02) in mice expressing native or inactive HL compared to luciferase controls, the fractional catabolic rates (FCR) of [125I-labeled] apoB- very low density lipoprotein (VLDL) in all three groups of mice were similar (P > 0.4, all) indicating selective cholesterol uptake. Hepatic uptake of [3H]cholesteryl ether from VLDL was greater in mice expressing either native HL (87%) or inactive HL-145G (72%) compared to luciferase controls (56%). Our combined findings are consistent 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 hypothesize that one of these pathways may involve the interaction of HL with cell surface receptors, such as scavenger receptor (SR)-BI, that mediate the selective uptake of cholesteryl esters.
authors.affiliation: Molecular Disease Branch, National Heart, Lung, and Blood Institutes, National Institues of Health, Bethesda, Maryland 20892-1666, USA.
authors.forename: M J
authors.initials: MJ
authors.lastname: Amar
authors.forename: K A
authors.initials: KA
authors.lastname: Dugi
authors.forename: C C
authors.initials: CC
authors.lastname: Haudenschild
authors.forename: R D
authors.initials: RD
authors.lastname: Shamburek
authors.forename: B
authors.initials: B
authors.lastname: Foger
authors.forename: M
authors.initials: M
authors.lastname: Chase
authors.forename: A
authors.initials: A
authors.lastname: Bensadoun
authors.forename: R F
authors.initials: RF
authors.lastname: Hoyt
authors.forename: H B
authors.initials: HB
authors.lastname: Brewer
authors.forename: S
authors.initials: S
authors.lastname: Santamarina-Fojo
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency; D002384:Catalysis; D002788:Cholesterol Esters / Q000378:metabolism*; D005822:Genetic Vectors; D008074:Lipoproteins / Q000378:metabolism*; D008099:Liver / Q000201:enzymology*; D008297:Male; D051379:Mice
chemical_list: D001057:Apolipoproteins E; D002788:Cholesterol Esters; D008074:Lipoproteins