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Journal of Lipid Research, Vol. 45, 1475-1481, August 2004
Copyright © 2004 by American Society for Biochemistry and Molecular Biology
,**
* 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
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