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

The VLDL receptor (VLDLr) is involved in tissue delivery of VLDL-triglyceride (TG)-derived FEN 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 [H-3]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 [C-14]FFA, indicating that the VLDLr facilitates postprandial LPL-mediated TG hydrolysis rather than mediating FEN uptake. We conclude that the VLDLr plays a major role in the metabolism of postprandial lipo-proteins by enhancing LPL-mediated TG hydrolysis. - Goudriaan,J. R., S. M. S. Espirito Santo, P.J. Voshol, B. Tensink, K. W. van Dijk, B.J. M. van Vlijmen, J. A. Romijn, L. M. Havekes, and P. C. N. Rensen. The VLDL receptor plays a major role in chylomicron metabolism by enhancing LPL-mediated triglyceride hydrolysis.