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.
“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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de Weijer, B. A., Aarts, E. O., Janssen, I. M. C., Berends, F. J., van de Laar, A. W. J. M., Kaasjager, K. A. H., Ackermans, M. T., Fliers, E., & Serlie, M. J. M. (2013) · Obesity · doi:10.1002/oby.20220 · Cited by 37 · see citing works
Tsekouras, Y. E., Magkos, F., Prentzas, K. I., Basioukas, K. N., Matsama, S. G., Yanni, A. E., Kavouras, S. A., & Sidossis, L. S. (2008) · Clinical Science · doi:10.1042/cs20080078 · Cited by 37 · see citing works
Smith, G. I., Reeds, D. N., Okunade, A. L., Patterson, B. W., & Mittendorfer, B. (2014) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2013-4470 · Cited by 37 · see citing works
Self-citationMagkos, F., Fabbrini, E., Korenblat, K., Okunade, A. L., Patterson, B. W., & Klein, S. J. (2010) · International Journal of Obesity · doi:10.1038/ijo.2010.265 · Cited by 36 · see citing works
Self-citationKinetic studies to investigate lipoprotein metabolism
Borén, J., Taskinen, M., & Adiels, M. (2011) · Journal of Internal Medicine · doi:10.1111/j.1365-2796.2011.02497.x · Cited by 35 · see citing works
Cade, W. T., Reeds, D. N., Mittendorfer, B., Patterson, B. W., Powderly, W. G., Klein, S., & Yarasheski, K. E. (2006) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00300.2006 · Cited by 34 · see citing works
Self-citationWang, X., Smith, G. I., Patterson, B. W., Reeds, D. N., Kampelman, J., Magkos, F., & Mittendorfer, B. (2012) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00533.2011 · Cited by 34 · see citing works
Self-citationMagkos, F., Fabbrini, E., Patterson, B. W., Eagon, J. C., & Klein, S. (2011) · Metabolism · doi:10.1016/j.metabol.2011.03.019 · Cited by 33 · see citing works
Self-citationInsulin activation of plasma non-esterified fatty acid uptake in metabolic syndrome
Ramos-Roman, M., Lapidot, S. A., Phair, R., & Parks, E. (2012) · Arteriosclerosis, Thrombosis and Vascular Biology · doi:10.1161/atvbaha.112.250019 · Cited by 30 · see citing works
HORMONE MEASUREMENT GUIDELINES: Tracing lipid metabolism: the value of stable isotopes
Umpleby, A. M. (2015) · Journal of Endocrinology · doi:10.1530/joe-14-0610 · Cited by 31 · see citing works
Comprehensive Lipoprotein Characterization Using Lipidomics Analysis of Human Plasma
Christinat, N., & Masoodi, M. (2017) · Journal of Proteome Research · doi:10.1021/acs.jproteome.7b00236 · Cited by 31 · see citing works
Barrett, P. H. R., & Watts, G. F. (2003) · Current Opinion in Lipidology · doi:10.1097/00041433-200302000-00011 · Cited by 31 · see citing works
Sørensen, L. P., Gormsen, L. C., & Nielsen, S. (2009) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00366.2009 · Cited by 30 · see citing works
Increased VLDL-TAG Turnover during and after Acute Moderate-Intensity Exercise
Morio, B., Holmbäck, U. C., Gore, D. C., & Wolfe, R. R. (2004) · Medicine & Science in Sports & Exercise · doi:10.1249/01.mss.0000126498.04454.c0 · Cited by 30 · see citing works
Acute Effects of Exercise and Calorie Restriction on Triglyceride Metabolism in Women
Bellou, E., Siopi, A., Galani, M., Maraki, M. I., Tsekouras, Y. E., Panagiotakos, D. B., Kavouras, S. A., Magkos, F., & Sidossis, L. S. (2013) · Medicine & Science in Sports & Exercise · doi:10.1249/mss.0b013e318278183e · Cited by 29 · see citing works
Ramakrishnan, R. (2006) · Journal of Lipid Research · doi:10.1194/jlr.m600302-jlr200 · Cited by 28 · see citing works
Basak, J. M., Kim, J., Pyatkivskyy, Y., Wildsmith, K. R., Jiang, H., Parsadanian, M., Patterson, B. W., Bateman, R. J., & Holtzman, D. M. (2012) · Molecular Neurodegeneration · doi:10.1186/1750-1326-7-14 · Cited by 27 · see citing works
Self-citationFabbrini, E., Magkos, F., Patterson, B. W., Mittendorfer, B., & Klein, S. (2012) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2011-2777 · Cited by 27 · see citing works
Self-citationEffect of high-intensity interval exercise on basal triglyceride metabolism in non-obese men
Bellou, E., Magkos, F., Kouka, T., Bouchalaki, E., Sklaveniti, D., Maraki, M. I., Tsekouras, Y. E., Panagiotakos, D. B., Kavouras, S. A., & Sidossis, L. S. (2013) · Applied Physiology, Nutrition, and Metabolism · doi:10.1139/apnm-2012-0468 · Cited by 26 · see citing works
Bittel, A. J., Bittel, D. C., Mittendorfer, B., Patterson, B. W., Okunade, A. L., Yoshino, J., Porter, L. C., Abumrad, N. A., Reeds, D. N., & Cade, W. T. (2019) · Diabetologia · doi:10.1007/s00125-019-05070-x · Cited by 26 · see citing works
Self-citationMagkos, F., & Sidossis, L. S. (2004) · Current Opinion in Clinical Nutrition & Metabolic Care · doi:10.1097/00075197-200409000-00007 · Cited by 26 · see citing works
Salvador, A. F., Shyu, C., & Parks, E. J. (2022) · Experimental & Molecular Medicine · doi:10.1038/s12276-022-00838-5 · Cited by 24 · see citing works
High-content assays for evaluating cellular and hepatic diacylglycerol acyltransferase activity
Qi, J., Lang, W., Giardino, E. C., Caldwell, G. W., Smith, C., Minor, L. K., Darrow, A. L., Willemsens, G., DeWaepenaert, K., Roevens, P. W. M., et al. (2010) · Journal of Lipid Research · doi:10.1194/jlr.d008029 · Cited by 24 · see citing works
Systemic Free Fatty Acid Disposal Into Very Low-Density Lipoprotein Triglycerides
Koutsari, C., Mundi, M. S., Ali, A. H., Patterson, B. W., & Jensen, M. D. (2013) · Diabetes · doi:10.2337/db12-1557 · Cited by 21 · see citing works
Self-citationvan Schalkwijk, D. B., de Graaf, A. A., van Ommen, B., van Bochove, K., Rensen, P. C. N., Havekes, L. M., van de Pas, N. C. A., Hoefsloot, H. C. J., van der Greef, J., & Freidig, A. P. (2009) · Journal of Lipid Research · doi:10.1194/jlr.m800354-jlr200 · Cited by 21 · see citing works
Sullivan, S. A., Fabbrini, E., Horton, J. D., Korenblat, K., Patterson, B. W., & Klein, S. (2011) · Translational research · doi:10.1016/j.trsl.2011.06.006 · Cited by 20 · see citing works
Self-citationŠarac, I., Backhouse, K., Shojaee‐Moradie, F., Stolinski, M., Robertson, M. D., Bell, J. D., Thomas, E. L., Hovorka, R., Wright, J., & Umpleby, A. M. (2012) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2011-3248 · Cited by 20 · see citing works
Effect of hypothyroidism on kinetics of metabolism of very-low-density lipoprotein in mares
Frank, N., Sojka, J. E., Patterson, B. W., Wood, K. V., Bonham, C. C., & Latour, M. A. (2003) · American Journal of Veterinary Research · doi:10.2460/ajvr.2003.64.1052 · Cited by 20 · see citing works
Self-citationMagkos, F., Fabbrini, E., Mohammed, B. S., Patterson, B. W., Klein, S., & Mittendorfer, B. (2010) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2010-0341 · Cited by 19 · see citing works
Self-citationSmith, G. I., Magkos, F., Reeds, D. N., Okunade, A. L., Patterson, B. W., & Mittendorfer, B. (2013) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2013-1786 · Cited by 19 · see citing works
Self-citationBellou, E., Maraki, M. I., Magkos, F., Botonaki, H., Panagiotakos, D. B., Kavouras, S. A., & Sidossis, L. S. (2013) · PLoS ONE · doi:10.1371/journal.pone.0060251 · Cited by 18 · see citing works
Magkos, F., Patterson, B. W., Mohammed, B. S., & Mittendorfer, B. (2008) · Clinical Science · doi:10.1042/cs20080220 · Cited by 15 · see citing works
Self-citationMagkos, F., Fabbrini, E., McCrea, J., Patterson, B. W., Eagon, J. C., & Klein, S. (2009) · Diabetes Obesity and Metabolism · doi:10.1111/j.1463-1326.2009.01191.x · Cited by 16 · see citing works
Self-citationSips, F. L. P., Tiemann, C. A., Oosterveer, M. H., Groen, A. K., Hilbers, P. A. J., & van Riel, N. A. W. (2014) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1003579 · Cited by 16 · see citing works
Body composition determines direct FFA storage pattern in overweight women
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 · see citing works
Miller, B. V., Patterson, B. W., Okunade, A. L., & Klein, S. (2012) · Journal of Lipid Research · doi:10.1194/jlr.p030593 · Cited by 15 · see citing works
Self-citationChan, D. C., Barrett, P. H. R., & Watts, G. F. (2004) · PubMed Central · Cited by 15 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 13 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
Self-citationKinetic Studies to Elucidate Impaired Metabolism of Triglyceride-rich Lipoproteins in Humans
Adiels, M., Mardinoğlu, A., Taskinen, M., & Borén, J. (2015) · Frontiers in Physiology · doi:10.3389/fphys.2015.00342 · Cited by 11 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
Self-citation
- 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
- Health Sciences › Medicine › Surgery › 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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