Title
The VLDL receptor plays a major role in chylomicron metabolism by enhancing LPL-mediated triglyceride hydrolysis
Author
Gaubius Instituut TNO
Goudriaan, J.R.
Espirito Santo, S.M.S.
Voshol, P.J.
Teusink, B.
van Dijk, K.W.
van Vlijmen, B.J.M.
Romijn, J.A.
Havekes, L.M.
Rensen, P.C.N.
Publication year
2004
Abstract
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
Subject
Biomedical Research
Adipose tissue
Free fatty acids
Lipoprotein lipase
Postprandial lipid metabolism
Transgenic mice
Very low density lipoprotein-like emulsion
Albumin
Carbon 14
Chylomicron
Fatty acid
Lipoprotein lipase
Triacylglycerol
Very low density lipoprotein
Very low density lipoprotein receptor
Animal experiment
Animal tissue
Bolus injection
Continuous infusion
Controlled study
Diet restriction
Emulsion
Enzyme activity
Fatty acid transport
Female
Half life time
Lipid blood level
Lipid hydrolysis
Lipid metabolism
Lipolysis
Mouse
Nonhuman
Plasma clearance
Postprandial state
Protein expression
Transgenic mouse
Adipose Tissue
Albumins
Animals
Chylomicrons
Fatty Acids, Nonesterified
Mice
Receptors, LDL
Triglycerides
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DOI
https://doi.org/10.1194/jlr.m400009-jlr200
TNO identifier
237933
ISSN
0022-2275
Source
Journal of Lipid Research, 45 (45), 1475-1481
Document type
article