|
Journal of Lipid Research, Vol. 41, 2094-2099, December 2000
Copyright © 2000 by Lipid Research, Inc.
In vivo evidence of a role for hepatic lipase in human apoB-containing lipoprotein metabolism, independent of its lipolytic activity
Alberto Zambona,
Samir S. Deebb,
Andre Bensadounc,
Karen E. Fostera, and
John D. Brunzella
a Division of Metabolism, Endocrinology, and Nutrition, Department of Medicine, University of Washington, Seattle, WA 98195
b Division of Medical Genetics, Department of Genetics, University of Washington, Seattle, WA 98195
c Division of Nutritional Sciences, Cornell University, Ithaca, NY 14853
Correspondence to:
John D. Brunzell
Hepatic lipase (HL) is a key player in lipoprotein metabolism by modulating, through its lipolytic activity, the triglyceride (TG) and phospholipid content of apolipoprotein B (apoB)-containing lipoproteins and of high density lipoproteins (HDL), thereby affecting their size and density. A new and separate role has been suggested for HL in cellular lipoprotein metabolism, in which it serves as a ligand promoting cellular uptake of apoB-containing remnant lipoproteins and HDL. We tested the hypothesis that HL has both a lipolytic and a nonlipolytic role in human lipoprotein metabolism, by measuring lipid plasma concentrations, lipoprotein density distribution by density gradient ultracentrifugation, and lipoprotein composition, in three subjects with HL deficiency: two of the patients (S-1 and S-3) were characterized as having neither plasma HL activity nor detectable HL protein; the third subject (S-2) had no plasma HL activity but a detectable amount (35.5 ng/ml) of HL protein. All HL-deficient subjects showed a severalfold increase in lipoprotein TG content across the lipoprotein density spectrum [very low density lipoprotein (VLDL), intermediate density lipoprotein (IDL), low density lipoprotein (LDL), and HDL] as compared with control subjects. They also had remarkably more buoyant LDL particles (LDL-Rf = 0.342;0.394) as compared with the control subjects (LDL-Rf = 0.303). Subjects S-1 and S-3 (no HL activity or protein) presented with a distinct increase in cholesterol and apoB levels in the IDL and VLDL density range as compared with patient S-2, with detectable HL protein, and the control subjects.
This study provides evidence in humans that HL indeed plays an important role in lipoprotein metabolism independent of its enzymatic activity: in particular, inactive HL protein appears to affect VLDL and IDL particle concentration, whereas HL enzymatic activity seems to influence VLDL-, IDL-, LDL-, and HDL-TG content and their physical properties. Zambon, A., S. S. Deeb, A. Bensadoun, K. E. Foster, and J. D. Brunzell. In vivo evidence of a role for hepatic lipase in human apoB-containing lipoprotein metabolism, independent of its lipolytic activity. J. Lipid Res. 2000. 41: 2094;2099.
Supplementary key words:
remnant lipoprotein LDL density, HDL cholesterol

CiteULike Complore Connotea Del.icio.us Digg Reddit Technorati What's this?
This article has been cited by other articles:

|
 |

|
 |
 
S. Imamura, J. Kobayashi, K. Nakajima, S. Sakasegawa, A. Nohara, T. Noguchi, M. A. Kawashiri, A. Inazu, S. S. Deeb, H. Mabuchi, et al.
A novel method for measuring human lipoprotein lipase and hepatic lipase activities in postheparin plasma
J. Lipid Res.,
July 1, 2008;
49(7):
1431 - 1437.
[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]
|
 |
|

|
 |

|
 |
 
L. E. Rufibach, S. A. Duncan, M. Battle, and S. S. Deeb
Transcriptional regulation of the human hepatic lipase (LIPC) gene promoter
J. Lipid Res.,
July 1, 2006;
47(7):
1463 - 1477.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
N. Stefan, S. Schafer, F. Machicao, J. Machann, F. Schick, C. D. Claussen, M. Stumvoll, H.-U. Haring, and A. Fritsche
Liver Fat and Insulin Resistance Are Independently Associated with the -514C>T Polymorphism of the Hepatic Lipase Gene
J. Clin. Endocrinol. Metab.,
July 1, 2005;
90(7):
4238 - 4243.
[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]
|
 |
|

|
 |

|
 |
 
R. J. Brown, A. Gauthier, R. J. Parks, R. McPherson, D. L. Sparks, J. R. Schultz, and Z. Yao
Severe Hypoalphalipoproteinemia in Mice Expressing Human Hepatic Lipase Deficient in Binding to Heparan Sulfate Proteoglycan
J. Biol. Chem.,
October 8, 2004;
279(41):
42403 - 42409.
[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
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]
|
 |
|

|
 |

|
 |
 
J. E. Hokanson, M. I. Kamboh, S. Scarboro, R. H. Eckel, and R. F. Hamman
Effects of the Hepatic Lipase Gene and Physical Activity on Coronary Heart Disease Risk
Am. J. Epidemiol.,
November 1, 2003;
158(9):
836 - 843.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
I. V. Fuki, N. Blanchard, W. Jin, D. H. L. Marchadier, J. S. Millar, J. M. Glick, and D. J. Rader
Endogenously Produced Endothelial Lipase Enhances Binding and Cellular Processing of Plasma Lipoproteins via Heparan Sulfate Proteoglycan-mediated Pathway
J. Biol. Chem.,
September 5, 2003;
278(36):
34331 - 34338.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. S. Deeb, A. Zambon, M. C. Carr, A. F. Ayyobi, and J. D. Brunzell
Hepatic lipase and dyslipidemia: interactions among genetic variants, obesity, gender, and diet
J. Lipid Res.,
July 1, 2003;
44(7):
1279 - 1286.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. F. Ayyobi, S. H. McGladdery, M. J. McNeely, M. A. Austin, A. G. Motulsky, and J. D. Brunzell
Small, Dense LDL and Elevated Apolipoprotein B Are the Common Characteristics for the Three Major Lipid Phenotypes of Familial Combined Hyperlipidemia
Arterioscler Thromb Vasc Biol,
July 1, 2003;
23(7):
1289 - 1294.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
T. L. McIlhargey, Y. Yang, H. Wong, and J. S. Hill
Identification of a Lipoprotein Lipase Cofactor-binding Site by Chemical Cross-linking and Transfer of Apolipoprotein C-II-responsive Lipolysis from Lipoprotein Lipase to Hepatic Lipase
J. Biol. Chem.,
June 13, 2003;
278(25):
23027 - 23035.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
K. Winkler, B. Wetzka, M. M. Hoffmann, I. Friedrich, M. Kinner, M. W. Baumstark, H.-P. Zahradnik, H. Wieland, and W. Marz
Triglyceride-Rich Lipoproteins Are Associated with Hypertension in Preeclampsia
J. Clin. Endocrinol. Metab.,
March 1, 2003;
88(3):
1162 - 1166.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
I. I.L. Berk-Planken, N. Hoogerbrugge, R. P. Stolk, A. H. Bootsma, and H. Jansen
Atorvastatin Dose-Dependently Decreases Hepatic Lipase Activity in Type 2 Diabetes: Effect of sex and the LIPC promoter variant
Diabetes Care,
February 1, 2003;
26(2):
427 - 432.
[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]
|
 |
|

|
 |

|
 |
 
E. Faggin, A. Zambon, M. Puato, S. S. Deeb, S. Bertocco, S. Sartore, G. Crepaldi, A. C. Pessina, and P. Pauletto
Association between the -514 c->t polymorphism of the hepatic lipase gene promoter and unstable carotid plaque in patients with severe carotid artery stenosis
J. Am. Coll. Cardiol.,
September 18, 2002;
40(6):
1059 - 1066.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
H. Jansen, A. J. M. Verhoeven, and E. J. G. Sijbrands
Hepatic lipase: a pro- or anti-atherogenic protein?
J. Lipid Res.,
September 1, 2002;
43(9):
1352 - 1362.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. J. Murdoch, M. C. Carr, H. Kennedy, J. D. Brunzell, and J. J. Albers
Selective and independent associations of phospholipid transfer protein and hepatic lipase with the LDL subfraction distribution
J. Lipid Res.,
August 1, 2002;
43(8):
1256 - 1263.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
H. Gonzalez-Navarro, Z. Nong, L. Freeman, A. Bensadoun, K. Peterson, and S. Santamarina-Fojo
Identification of mouse and human macrophages as a site of synthesis of hepatic lipase
J. Lipid Res.,
May 1, 2002;
43(5):
671 - 675.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. E. Hokanson, S. Cheng, J. K. Snell-Bergeon, B. A. Fijal, M. A. Grow, C. Hung, H. A. Erlich, J. Ehrlich, R. H. Eckel, and M. Rewers
A Common Promoter Polymorphism in the Hepatic Lipase Gene (LIPC-480C>T) Is Associated With an Increase in Coronary Calcification in Type 1 Diabetes
Diabetes,
April 1, 2002;
51(4):
1208 - 1213.
[Abstract]
[Full Text]
[PDF]
|
 |
|
Copyright © 2000 by the American Society for Biochemistry and Molecular Biology.
|
Advertisement
Advertisement
|