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 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.
Goudriaan
Jeltje R
JR
Institute for Applied Scientific Research Prevention and Health, Gaubius Laboratory, 2301 CE Leiden, The Netherlands.
Espirito Santo
Sonia M S
SM
Voshol
Peter J
PJ
Teusink
Bas
B
van Dijk
Ko Willems
KW
van Vlijmen
Bart J M
BJ
Romijn
Johannes A
JA
Havekes
Louis M
LM
Rensen
Patrick C N
PC
D000273:Adipose Tissue / Q000378:metabolism; D000418:Albumins / Q000378:metabolism; D000818:Animals; D002914:Chylomicrons / Q000378:metabolism*; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D008071:Lipoprotein Lipase / Q000378:metabolism*; D051379:Mice; D011973:Receptors, LDL / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D014280:Triglycerides / Q000378:metabolism*
D000418:Albumins; D002914:Chylomicrons; D005230:Fatty Acids, Nonesterified; D011973:Receptors, LDL; D014280:Triglycerides; C036053:VLDL receptor; D008071:Lipoprotein Lipase