The VLDL receptor plays a major role in chylomicron metabolism by enhancing LPL-mediated triglyceride hydrolysis
Open accessAbstract
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.
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In the periphery, VLDLR has a clear role facilitating lipolytic activity of LPL.
“In the periphery, VLDLR has a clear role facilitating lipolytic activity of LPL20,22”
From IDOL regulates systemic energy balance through control of neuronal VLDLR expression (2019) · cites this paper as [22]
Prior mechanistic analyses suggested that VLDLR in the periphery acts in the endothelium to enhance lipoprotein lipase-dependent hydrolysis of triglycerides.
“Prior mechanistic analyses have suggested that VLDLR in the periphery acts in the endothelium to enhance lipoprotein lipase-dependent hydrolysis of triglycerides20–23.”
From IDOL regulates systemic energy balance through control of neuronal VLDLR expression (2019) · cites this paper as [22]
Whole-body deletion of VLDLR is protective against diet-induced obesity.
“Whole body deletion of VLDLR has previously been shown to be protective against diet-induced obesity22,27,28.”
From IDOL regulates systemic energy balance through control of neuronal VLDLR expression (2019) · cites this paper as [22]
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Cites
A RAPID METHOD OF TOTAL LIPID EXTRACTION AND PURIFICATION
Bligh, E. G., & Dyer, W. J. (1959) · Canadian Journal of Biochemistry and Physiology · doi:10.1139/o59-099 · Cited by 54,751 · see citing works
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Ting, H. J., Stice, J. P., Schaff, U. Y., Hui, D. Y., Rutledge, J. C., Knowlton, A. A., Passerini, A. G., & Simon, S. I. (2007) · Circulation Research · doi:10.1161/01.res.0000258023.76515.a3 · Cited by 138 · see citing works
Foley, E. M., Gordts, P. L. S. M., Stanford, K. I., Gonzales, J. C., Lawrence, R., Stoddard, N., & Esko, J. D. (2013) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/atvbaha.113.301637 · Cited by 77 · see citing works
IDOL regulates systemic energy balance through control of neuronal VLDLR expression
Lee, S. D., Priest, C., Bjursell, M., Gao, J., Arneson, D. V., Ahn, I. S., Diamante, G., van Veen, J. E., Massa, M. G., Calkin, A. C., et al. (2019) · Nature Metabolism · doi:10.1038/s42255-019-0127-7 · Cited by 26 · see citing works
- Authors
- Goudriaan, J. R., Santo, S. M. S. E., Voshol, P. J., Teusink, B., van Dijk, K. W., van Vlijmen, B. J. M., Romijn, J. A., Havekes, L. M., & Rensen, P. C. N.
- Affiliations
- Leiden University Medical Center (NL)
- Corresponding author
- Voshol, Peter J.
- Venue
- Journal of Lipid Research
- Publisher
- Elsevier BV
- Published
- 2004-08
- Volume
- 45
- Issue
- 8
- Pages
- 1475-1481
- ISSN
- 0022-2275 (ISSN-L)
- OpenAlex
- W2109896814
- Cited by
- 100
- References
- 1
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 3 · 2023: 5 · 2022: 6 · 2021: 3 · 2020: 2 · 2019: 7 · 2018: 3 · 2017: 5 · 2016: 2 · 2015: 1 · 2014: 3 · 2013: 3 · 2012: 6
- FWCI
- 3.93
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Lipid Research (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion)
- TNO Repository (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Repository hosted by TU Delft Library (TU Delft) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- Funders
- Diabetes Fonds
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Keywords
- VLDL receptor, chylomicron metabolism, lipoprotein lipase, lipolysis, postprandial lipoproteins, chylomicron clearance, plasma triglycerides, free fatty acids
- MeSH terms
- Adipose Tissue, Albumins, Animals, Chylomicrons, Fatty Acids, Nonesterified, Lipoprotein Lipase, Receptors, LDL, Triglycerides, Mice
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