HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) An erratum has been published Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Dichek, H. L. Articles by Mahley, R. W. Search for Related Content PubMed PubMed Citation Articles by Dichek, H. L. Articles by Mahley, R. W. Social Bookmarking                      What's this?

Journal of Lipid Research, Vol. 42, 201-210, February 2001
Copyright © 2001 by Lipid Research, Inc.

Original Article

Hepatic lipase overexpression lowers remnant and LDL levels by a noncatalytic mechanism in LDL receptor-deficient mice

Correspondence to: Helén L. Dichek, To whom correspondence should be addressed., hdichek{at}chori.org (E-mail)

To address the role of the noncatalytic ligand function of hepatic lipase (HL) in low density lipoprotein (LDL) receptor-mediated lipoprotein metabolism, we characterized transgenic mice lacking the LDL receptor (LDLR) that express either catalytically active (Ldlr^-/-HL) or inactive (Ldlr^-/-HL^S145G) human HL on both chow and high fat diets and compared them with nontransgenic Ldlr^-/- mice. In mice fed a chow diet, apolipoprotein (apo)B-containing lipoprotein levels were 40;–60% lower in Ldlr^-/-HL and Ldlr^-/-HL^S145G mice than in Ldlr^-/- mice. This decrease was mainly reflected by decreased apoB-48 levels in the Ldlr^-/-HL mice and by decreased apoB-100 levels in Ldlr^-/- HL^S145G mice. These findings indicate that HL can reduce apoB-100-containing lipoproteins through a noncatalytic ligand activity that is independent of the LDLR. Cholesterol enrichment of the apoB-containing lipoproteins induced by feeding Ldlr^-/-HL and Ldlr^-/-HL^S145G mice a cholesterol-enriched high fat (Western) diet resulted in parallel decreases in both apoB-100 and apoB-48 levels, indicating that HL is particularly efficient at reducing cholesterol-enriched apoB-containing lipoproteins through both catalytic and noncatalytic mechanisms.

These data suggest that the noncatalytic function of HL provides an alternate clearance pathway for apoB-100- and apoB-48-containing lipoproteins that is independent of the LDLR and that contributes to the clearance of high density lipoproteins. — Dichek, H. L., S. M. Johnson, H. Akeefe, G. T. Lo, E. Sage, C. E. Yap, and R. W. Mahley. Hepatic lipase overexpression lowers remnant and LDL levels by a noncatalytic mechanism in LDL receptor-deficient mice. J. Lipid Res. 2001. 42: 201;–210.

Supplementary key words: noncatalytic function, ligand function, apoB-100, FPLC, Western diet, phospholipase A1 activity

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				A. Isaacs, Y. S. Aulchenko, A. Hofman, E. J. G. Sijbrands, F. A. Sayed-Tabatabaei, O. H. Klungel, A.-H. Maitland-van der Zee, B. H. Ch. Stricker, B. A. Oostra, J. C. M. Witteman, et al. Epistatic Effect of Cholesteryl Ester Transfer Protein and Hepatic Lipase on Serum High-Density Lipoprotein Cholesterol Levels J. Clin. Endocrinol. Metab., July 1, 2007; 92(7): 2680 - 2687. [Abstract] [Full Text] [PDF]

				J. C. Lo, Y. Wang, A. V. Tumanov, M. Bamji, Z. Yao, C. A. Reardon, G. S. Getz, and Y.-X. Fu Lymphotoxin {beta} Receptor-Dependent Control of Lipid Homeostasis Science, April 13, 2007; 316(5822): 285 - 288. [Abstract] [Full Text] [PDF]

				L. Freeman, M. J. A. Amar, R. Shamburek, B. Paigen, H. B. Brewer Jr., S. Santamarina-Fojo, and H. Gonzalez-Navarro Lipolytic and ligand-binding functions of hepatic lipase protect against atherosclerosis in LDL receptor-deficient mice J. Lipid Res., January 1, 2007; 48(1): 104 - 113. [Abstract] [Full Text] [PDF]

				P. Degrace, B. Moindrot, I. Mohamed, J. Gresti, Z.-Y. Du, J.-M. Chardigny, J.-L. Sebedio, and P. Clouet Upregulation of liver VLDL receptor and FAT/CD36 expression in LDLR-/- apoB100/100 mice fed trans-10,cis-12 conjugated linoleic acid J. Lipid Res., December 1, 2006; 47(12): 2647 - 2655. [Abstract] [Full Text] [PDF]

				S. L. Karackattu, B. Trigatti, and M. Krieger Hepatic Lipase Deficiency Delays Atherosclerosis, Myocardial Infarction, and Cardiac Dysfunction and Extends Lifespan in SR-BI/Apolipoprotein E Double Knockout Mice Arterioscler. Thromb. Vasc. Biol., March 1, 2006; 26(3): 548 - 554. [Abstract] [Full Text] [PDF]

				S.-J. Lee, S. Kadambi, K. C-W. Yu, C. David, S. Azhar, A. D. Cooper, and S. Y. Choi Removal of chylomicron remnants in transgenic mice overexpressing normal and membrane-anchored hepatic lipase J. Lipid Res., January 1, 2005; 46(1): 27 - 35. [Abstract] [Full Text] [PDF]

				H. Gonzalez-Navarro, Z. Nong, M. J. A. Amar, R. D. Shamburek, J. Najib-Fruchart, B. J. Paigen, H. B. Brewer Jr., and S. Santamarina-Fojo The Ligand-binding Function of Hepatic Lipase Modulates the Development of Atherosclerosis in Transgenic Mice J. Biol. Chem., October 29, 2004; 279(44): 45312 - 45321. [Abstract] [Full Text] [PDF]

				S. Santamarina-Fojo, H. Gonzalez-Navarro, L. Freeman, E. Wagner, and Z. Nong Hepatic Lipase, Lipoprotein Metabolism, and Atherogenesis Arterioscler. Thromb. Vasc. Biol., October 1, 2004; 24(10): 1750 - 1754. [Abstract] [Full Text] [PDF]

				H. L. Dichek, K. Qian, and N. Agrawal Divergent Effects of the Catalytic and Bridging Functions of Hepatic Lipase on Atherosclerosis Arterioscler. Thromb. Vasc. Biol., September 1, 2004; 24(9): 1696 - 1702. [Abstract] [Full Text] [PDF]

				U. C. Broedl, C. Maugeais, J. S. Millar, W. Jin, R. E. Moore, I. V. Fuki, D. Marchadier, J. M. Glick, and D. J. Rader Endothelial Lipase Promotes the Catabolism of ApoB-Containing Lipoproteins Circ. Res., June 25, 2004; 94(12): 1554 - 1561. [Abstract] [Full Text] [PDF]

				A. E. Cozen, H. Moriwaki, M. Kremen, M. B. DeYoung, H. L. Dichek, K. I. Slezicki, S. G. Young, M. Veniant, and D. A. Dichek Macrophage-Targeted Overexpression of Urokinase Causes Accelerated Atherosclerosis, Coronary Artery Occlusions, and Premature Death Circulation, May 4, 2004; 109(17): 2129 - 2135. [Abstract] [Full Text] [PDF]

				H. L. Dichek, K. Qian, and N. Agrawal The bridging function of hepatic lipase clears plasma cholesterol in LDL receptor-deficient "apoB-48-only" and "apoB-100-only" mice J. Lipid Res., March 1, 2004; 45(3): 551 - 560. [Abstract] [Full Text] [PDF]

				M. Rizzo, J. M. Taylor, C. M. Barbagallo, K. Berneis, P. J. Blanche, and R. M. Krauss Effects on Lipoprotein Subclasses of Combined Expression of Human Hepatic Lipase and Human apoB in Transgenic Rabbits Arterioscler. Thromb. Vasc. Biol., January 1, 2004; 24(1): 141 - 146. [Abstract] [Full Text] [PDF]

				U. C. Broedl, C. Maugeais, D. Marchadier, J. M. Glick, and D. J. Rader Effects of Nonlipolytic Ligand Function of Endothelial Lipase on High Density Lipoprotein Metabolism in Vivo J. Biol. Chem., October 17, 2003; 278(42): 40688 - 40693. [Abstract] [Full Text] [PDF]

				R. L. Raffai, A. H. Hasty, Y. Wang, S. E. Mettler, D. A. Sanan, M. F. Linton, S. Fazio, and K. H. Weisgraber Hepatocyte-derived ApoE Is More Effective than Non-hepatocyte-derived ApoE in Remnant Lipoprotein Clearance J. Biol. Chem., March 21, 2003; 278(13): 11670 - 11675. [Abstract] [Full Text] [PDF]

				S. Y. Choi, K.-i. Hirata, T. Ishida, T. Quertermous, and A. D. Cooper Endothelial lipase: a new lipase on the block J. Lipid Res., November 1, 2002; 43(11): 1763 - 1769. [Abstract] [Full Text] [PDF]