The VLDL receptor plays a major role in chylomicron metabolism by enhancing LPL-mediated triglyceride hydrolysis
article
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. Chemicals / CAS: carbon 14, 14762-75-5; lipoprotein lipase, 83137-80-8, 9004-02-8; Albumins; Chylomicrons; Fatty Acids, Nonesterified; Lipoprotein Lipase, EC 3.1.1.34; Receptors, LDL; Triglycerides; VLDL receptor
Topics
Biomedical ResearchAdipose tissueFree fatty acidsLipoprotein lipasePostprandial lipid metabolismTransgenic miceVery low density lipoprotein-like emulsionAlbuminCarbon 14ChylomicronFatty acidLipoprotein lipaseTriacylglycerolVery low density lipoproteinVery low density lipoprotein receptorAnimal experimentAnimal tissueBolus injectionContinuous infusionControlled studyDiet restrictionEmulsionEnzyme activityFatty acid transportFemaleHalf life timeLipid blood levelLipid hydrolysisLipid metabolismLipolysisMouseNonhumanPlasma clearancePostprandial stateProtein expressionTransgenic mouseAdipose TissueAlbuminsAnimalsChylomicronsFatty Acids, NonesterifiedMiceReceptors, LDLTriglycerides
TNO Identifier
237933
ISSN
00222275
Source
Journal of Lipid Research, 45(8), pp. 1475-1481.
Pages
1475-1481