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Use of stable isotopically labeled tracers to measure very low density lipoprotein-triglyceride turnover
Open accessAbstract
Tracer methods for VLDL-TG kinetics vary in their ability to account for the effect of tracer recycling, which can influence the calculation of VLDL-TG fractional catabolic rates (FCRs). We evaluated a novel approach, involving stable isotopically labeled glycerol or palmitate tracers in conjunction with compartmental modeling, for measuring VLDL-TG kinetics in normolipidemic human subjects. When administered as a bolus simultaneously, both tracers provided identical VLDL-TG FCRs when the data were analyzed by a compartmental model that accounted for hepatic lipid tracer recycling, but not by non-compartmental analysis. The model-derived FCR was greater than that determined using a non-compartmental approach, and was 2- to 3-fold higher than that usually reported by using a bolus of radioactive [3H]glycerol. When palmitate tracer was given as a constant infusion, VLDL-TG turnover appeared 5-fold slower, because tracer recycling through hepatic lipid pools could not be resolved with the infusion protocol. We conclude that accounting for tracer recycling, particularly the contribution of hepatic glycerolipid pools, is essential to accurately measure VLDL-TG kinetics, and that bolus injection of stable isotopically labeled glycerol or palmitate tracers in conjunction with compartmental modeling analysis offers a reliable approach for measuring VLDL-TG kinetics.
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“At metabolic steady state, the fraction of the pool that is synthesized per unit time equals the fraction of the pool catabolized per unit time (FCR), which can be calculated as the negative of the slope of the natural log of TTR plotted over time [53].”
From Measurement of apolipoprotein E and amyloid β clearance rates in the mouse brain using bolus stable isotope labeling (2012) · cites this paper as [53]
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Søndergaard, E., Gormsen, L. C., Nellemann, B., Jensen, M., & Nielsen, S. (2012) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00015.2012 · Cited by 16
Miller, B. V., Patterson, B. W., Okunade, A. L., & Klein, S. (2012) · Journal of Lipid Research · doi:10.1194/jlr.p030593 · Cited by 15
Self-citationChan, D. C., Barrett, P. H. R., & Watts, G. F. (2004) · PubMed Central · Cited by 15
Chondronikola, M., Yoshino, J., Ramaswamy, R. S., Giardina, J. D., Laforest, R. A., Wahl, R. L., Patterson, B. W., Mittendorfer, B., & Klein, S. (2024) · Cell Reports Medicine · doi:10.1016/j.xcrm.2023.101370 · Cited by 15
Self-citationMcLaren, D. G., Wang, S.-P., Stout, S. J., Xie, D., Miller, P. L., Mendoza, V., Rosa, R. L., Castro‐Perez, J. M., Previs, S. F., Johns, D. G., et al. (2012) · Journal of Lipid Research · doi:10.1194/jlr.d030791 · Cited by 13
Notch-ligand expression by NALT dendritic cells regulates mucosal Th1- and Th2-type responses
Fukuyama, Y., Tokuhara, D., Sekine, S., Kataoka, K., Markham, J. D., Irwin, A. R., Moon, G. H., Tokuhara, Y., Fujihashi, K., Davydova, J., et al. (2011) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2011.12.046 · Cited by 13
Correlation of plasma metabolites with glucose and lipid fluxes in human insulin resistance
Hartstra, A. V., de Groot, P. F., Bastos, D. M., Levin, E., Serlie, M. J. M., Soeters, M. R., Pekmez, C. T., Dragsted, L. O., Ackermans, M. T., Groen, A. K., et al. (2020) · Obesity Science & Practice · doi:10.1002/osp4.402 · Cited by 12
McLaren, D. G., Previs, S. F., Phair, R. D., Stout, S. J., Xie, D., Chen, Y., Salituro, G., Xu, S. S., Castro‐Perez, J. M., Opiteck, G. J., et al. (2016) · Journal of Lipid Research · doi:10.1194/jlr.m063842 · Cited by 12
Wang, X., Magkos, F., Patterson, B. W., Reeds, D. N., Kampelman, J., & Mittendorfer, B. (2012) · European Journal of Endocrinology · doi:10.1530/eje-12-0180 · Cited by 13
Self-citationSidossis, L. S., Magkos, F., Mittendorfer, B., & Wolfe, R. R. (2003) · Clinical Nutrition · doi:10.1016/j.clnu.2003.11.006 · Cited by 12
Self-citationHuang, L., Deepak, P., Ciorba, M. A., Mittendorfer, B., Patterson, B. W., & Randolph, G. J. (2020) · Gastroenterology · doi:10.1053/j.gastro.2020.07.012 · Cited by 11
Self-citationKinetic Studies to Elucidate Impaired Metabolism of Triglyceride-rich Lipoproteins in Humans
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Adiels, M., Larsson, T. P., Sutton, P., Taskinen, M., Borén, J., & Fielding, B. A. (2010) · Rapid Communications in Mass Spectrometry · doi:10.1002/rcm.4422 · Cited by 11
Bohlin, K., Patterson, B. W., Spence, K. L., Merchak, A., Zozobrado, J. C. G., Zimmermann, L. J. I., Carnielli, V. P., & Hamvas, A. (2005) · Journal of Lipid Research · doi:10.1194/jlr.m400481-jlr200 · Cited by 11
Self-citationEffect of complete, lifelong ANGPTL3 deficiency on triglyceride-rich lipoprotein kinetics
Fappi, A., Patterson, B. W., Burks, K. H., Davidson, N. O., Vaisar, T., Kanter, J. E., Bornfeldt, K., Fisher, E. A., Goldberg, I. J., Stitziel, N. O., et al. (2025) · Cell Reports Medicine · doi:10.1016/j.xcrm.2025.102152 · Cited by 9
Self-citation
Metadata
- Authors
- Patterson, B. W., Mittendorfer, B., Elias, N., Satyanarayana, R., & Klein, S.
- Affiliations
- Washington University in St. Louis (US)
- Corresponding author
- Patterson, Bruce W.
- Venue
- Journal of Lipid Research
- Publisher
- Elsevier BV
- Published
- 2002-02
- Volume
- 43
- Issue
- 2
- Pages
- 223-233
- ISSN
- 0022-2275 (ISSN-L)
- OpenAlex
- W2253903755
- Cited by
- 118
- References
- 45
- Citations by year
- 2025: 1 · 2024: 2 · 2022: 3 · 2020: 4 · 2019: 2 · 2018: 1 · 2017: 1 · 2016: 1 · 2015: 4 · 2014: 4 · 2013: 11 · 2012: 15
- FWCI
- 5.70
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Lipid Research (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institutes of Health (5r01ca062177-05, 5p41rr000954-34, RR‐00036, DK56341)
- National Cancer Institute (CA62177)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK37948, DK56341, R01DK037948, P30DK056341)
- National Center for Research Resources (RR 00954, RR.00036)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Cholesterol and Lipid Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Keywords
- VLDL, triglyceride turnover, stable isotope tracers, fractional catabolic rate, compartmental modeling, non-compartmental analysis, bolus injection, continuous infusion, normolipidemic subjects
- MeSH terms
- Adult, Carbon Isotopes, Deuterium, Female, Glycerol, Humans, Infusions, Intravenous, Isotope Labeling, Kinetics, Lipoproteins, VLDL, Male, Palmitates, Triglycerides
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