title: Hepatic lipase affects both HDL and ApoB-containing lipoprotein levels in the mouse.
abstract: Transgenic mice were created overproducing a range of human HL (hHL) activities (4-23-fold increase) to further examine the role of hepatic lipase (HL) in lipoprotein metabolism. A 5-fold increase in heparin releasable HL activity was accompanied by moderate (approx. 20%) decreases in plasma total and high density lipoprotein (HDL) cholesterol and phospholipid (PL) but no significant change in triglyceride (TG). A 23-fold increase in HL activity caused a more significant decrease in plasma total and HDL cholesterol, PL and TG (77%, 64%, 60%, and 24% respectively), and a substantial decrease in lipoprotein lipids amongst IDL, LDL and HDL fractions. High levels of HL activity diminished the plasma concentration of apoA-I, A-II and apoE (76%, 48% and 75%, respectively). In contrast, the levels of apoA-IV-containing lipoproteins appear relatively resistant to increased titers of hHL activity. Increased hHL activity was associated with a progressive decrease in the levels and an increase in the density of LpAI and LpB48 particles. The increased rate of disappearance of 125I-labeled human HDL from the plasma of hHL transgenic mice suggests increased clearance of HDL apoproteins in the transgenic mice. The effect of increased HL activity on apoB100-containing lipoproteins was more complex. HL-deficient mice have substantially decreased apoB100-containing low density lipoproteins (LDL) compared to controls. Increased HL activity is associated with a transformation of the lipoprotein density profile from predominantly buoyant (VLDL/IDL) lipoproteins to more dense (LDL) fractions. Increased HL activity from moderate (4-fold) to higher (5-fold) levels decreased the levels of apoB100-containing particles. Thus, at normal to moderately high levels in the mouse, HL promotes the metabolism of both HDL and apoB-containing lipoproteins and thereby acts as a key determinant of plasma levels of both HDL and LDL.
authors.affiliation: Lipoprotein and Atherosclerosis Research Group, University of Ottawa Heart Institute, University of Ottawa, H445A, 1053 Carling Avenue, Ottawa, Ont. K1Y 4E9, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Braschi
authors.forename: N
authors.initials: N
authors.lastname: Couture
authors.forename: A
authors.initials: A
authors.lastname: Gambarotta
authors.forename: B R
authors.initials: BR
authors.lastname: Gauthier
authors.forename: C R
authors.initials: CR
authors.lastname: Coffill
authors.forename: D L
authors.initials: DL
authors.lastname: Sparks
authors.forename: N
authors.initials: N
authors.lastname: Maeda
authors.forename: J R
authors.initials: JR
authors.lastname: Schultz
mesh_terms: D000818:Animals; D001055:Apolipoproteins B / Q000097:blood*; D008076:Cholesterol, HDL / Q000097:blood; D004591:Electrophoresis, Polyacrylamide Gel; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D008049:Lipase / Q000235:genetics / Q000378:metabolism*; D008074:Lipoproteins / Q000097:blood*; D008075:Lipoproteins, HDL / Q000097:blood*; D008077:Lipoproteins, LDL / Q000097:blood; D008099:Liver / Q000201:enzymology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010743:Phospholipids / Q000097:blood; D012333:RNA, Messenger / Q000032:analysis; D013045:Species Specificity; D014018:Tissue Distribution
chemical_list: D001055:Apolipoproteins B; D008076:Cholesterol, HDL; D008074:Lipoproteins; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D010743:Phospholipids; D012333:RNA, Messenger; D006493:Heparin; D008049:Lipase