|
 |
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Journal of Lipid Research, Vol. 45, 1475-1481, August 2004
Copyright © 2004 by American Society for Biochemistry and Molecular Biology
The VLDL receptor plays a major role in chylomicron metabolism by enhancing LPL-mediated triglyceride hydrolysis
,**
* Institute for Applied Scientific Research Prevention and Health, Gaubius Laboratory, 2301 CE Leiden, The Netherlands
Department of Endocrinology and Diabetes, Leiden University Medical Center, 2300 RC Leiden, The Netherlands
Department of Cardiology and General Internal Medicine, Leiden University Medical Center, 2300 RC Leiden, The Netherlands
** Molecular Genetics and Cell Biology-Department of Human Genetics, Leiden University Medical Center, 2300 RC Leiden, The Netherlands
1 To whom correspondence should be addressed. e-mail: pj.voshol{at}pg.tno.nl
The VLDL receptor (VLDLr) is involved in tissue delivery of VLDL-triglyceride (TG)-derived FFA by facilitating the expression of lipoprotein lipase (LPL). However, vldlr–/– mice do not show altered plasma lipoprotein levels, despite reduced LPL expression. Because LPL activity is crucial in postprandial lipid metabolism, we investigated whether the VLDLr plays a role in chylomicron clearance. Fed plasma TG levels of vldlr–/– mice were 2.5-fold increased compared with those of vldlr+/+ littermates (1.20 ± 0.37 mM vs. 0.47 ± 0.18 mM; P < 0.001). Strikingly, an intragastric fat load led to a 9-fold increased postprandial TG response in vldlr–/– compared with vldlr+/+ mice (226 ± 188 mM/h vs. 25 ± 11 mM/h; P < 0.05). Accordingly, the plasma clearance of [3H]TG-labeled protein-free chylomicron-mimicking emulsion particles was delayed in vldlr–/– compared with vldlr+/+ mice (half-life of 12.0 ± 2.6 min vs. 5.5 ± 0.9 min; P < 0.05), with a 60% decreased uptake of label into adipose tissue (P < 0.05). VLDLr deficiency did not affect the plasma half-life and adipose tissue uptake of albumin-complexed [14C]FFA, indicating that the VLDLr facilitates postprandial LPL-mediated TG hydrolysis rather than mediating FFA uptake.
We conclude that the VLDLr plays a major role in the metabolism of postprandial lipoproteins by enhancing LPL-mediated TG hydrolysis.
Abbreviations: apoE, apolipoprotein E; HL, hepatic lipase; LDLr, LDL receptor; LPL, lipoprotein lipase; TG, triglyceride; VLDLr, VLDL receptor
Supplementary key words adipose tissue • free fatty acids • lipoprotein lipase • postprandial lipid metabolism • very low density lipoprotein-like emulsion • transgenic mice
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  L. Hu, C. C. van der Hoogt, S. M. S. Espirito Santo, R. Out, K. E. Kypreos, B. J. M. van Vlijmen, T. J. C. Van Berkel, J. A. Romijn, L. M. Havekes, K. W. van Dijk, et al. The hepatic uptake of VLDL in lrp-ldlr-/-vldlr-/- mice is regulated by LPL activity and involves proteoglycans and SR-BI J. Lipid Res., July 1, 2008; 49(7): 1553 - 1561. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. J. A. Moen, A. P. Tholens, P. J. Voshol, W. de Haan, L. M. Havekes, P. Gargalovic, A. J. Lusis, K. W. van Dyk, R. R. Frants, M. H. Hofker, et al. The Hyplip2 locus causes hypertriglyceridemia by decreased clearance of triglycerides J. Lipid Res., October 1, 2007; 48(10): 2182 - 2192. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Fergani, H. Oudart, J.-L. Gonzalez De Aguilar, B. Fricker, F. Rene, J.-F. Hocquette, V. Meininger, L. Dupuis, and J.-P. Loeffler Increased peripheral lipid clearance in an animal model of amyotrophic lateral sclerosis J. Lipid Res., July 1, 2007; 48(7): 1571 - 1580. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. J. Ting, J. P. Stice, U. Y. Schaff, D. Y. Hui, J. C. Rutledge, A. A. Knowlton, A. G. Passerini, and S. I. Simon Triglyceride-Rich Lipoproteins Prime Aortic Endothelium for an Enhanced Inflammatory Response to Tumor Necrosis Factor-{alpha} Circ. Res., February 16, 2007; 100(3): 381 - 390. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Claudel, B. Staels, and F. Kuipers The Farnesoid X Receptor: A Molecular Link Between Bile Acid and Lipid and Glucose Metabolism Arterioscler. Thromb. Vasc. Biol., October 1, 2005; 25(10): 2020 - 2030. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Iwasaki, S. Takahashi, M. Takahashi, Y. Zenimaru, T. Kujiraoka, M. Ishihara, M. Nagano, J. Suzuki, I. Miyamori, H. Naiki, et al. Deficiency of the Very Low-Density Lipoprotein (VLDL) Receptors in Streptozotocin-Induced Diabetic Rats: Insulin Dependency of the VLDL Receptor Endocrinology, August 1, 2005; 146(8): 3286 - 3294. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Bovenschen, K. Mertens, L. Hu, L. M. Havekes, and B. J. M. van Vlijmen LDL receptor cooperates with LDL receptor-related protein in regulating plasma levels of coagulation factor VIII in vivo Blood, August 1, 2005; 106(3): 906 - 912. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. M. S. E. Santo, P. C. N. Rensen, J. R. Goudriaan, A. Bensadoun, N. Bovenschen, P. J. Voshol, L. M. Havekes, and B. J. M. van Vlijmen Triglyceride-rich lipoprotein metabolism in unique VLDL receptor, LDL receptor, and LRP triple-deficient mice J. Lipid Res., June 1, 2005; 46(6): 1097 - 1102. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Duivenvoorden, B. Teusink, P. C. Rensen, J. A. Romijn, L. M. Havekes, and P. J. Voshol Apolipoprotein C3 Deficiency Results in Diet-Induced Obesity and Aggravated Insulin Resistance in Mice Diabetes, March 1, 2005; 54(3): 664 - 671. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Journal of Biological Chemistry |
| Molecular and Cellular Proteomics | ASBMB Today |