J. Lipid Res.
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A more recent version of this article appeared on August 1, 2004

Papers In Press, published online ahead of print May 16, 2004
J. Lipid Res., doi:10.1194/jlr.M400009-JLR200
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Submitted on January 13, 2004
Revised on May 3, 2004
Accepted on May 10, 2004

The VLDL receptor plays a major role in chylomicron metabolism by enhancing LPL-mediated triglyceride hydrolysis

Jeltje R. Goudriaan, Sonia M. S. Espirito Santo, Peter J. Voshol, Bas Teusink, Ko Willems van Dijk, Bart J. M. van Vlijmen, Johannes A. Romijn, Louis M. Havekes, and Patrick C. N. Rensen

TNO Prevention and Health, Leiden 2333 CK

Corresponding Author: 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. Since 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 to vldlr +/+ littermates (1.20 ± 0.37 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 to vldlr +/+ mice (226 ± 188 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 to vldlr +/+ mice (t½: 12.0 ± 2.6 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.


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