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

• DOI: 10.1194/jlr.m400009-jlr200
• Publication Date: 2004-07-14T23:30:31Z
• Authors: Jeltje R. Goudriaan; Sonia M. S. Espir...; Peter J. Voshol; Bas Teusink; Ko Willems van Dijk; Bart J.M. van Vli...; Johannes A. Romijn; Louis M. Havekes; Patrick C.N. Rensen
• Keywords: 0303 health sciences; lipoprotein lipase; free fatty acids; QD415-436; transgenic mice; Fatty Acids, Nonesterified; Biochemistry; adipose tissue; Lipoprotein Lipase; Mice; 03 medical and health sciences; Adipose Tissue; Receptors, LDL; postprandial lipid metabolism; very low density lipoprotein-like emulsion; Albumins; Chylomicrons; Animals; Triglycerides

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.