Effect of Severe Burn Injury on Substrate Cycling by Glucose and Fatty Acids
Abstract
Increases in metabolic rate and core temperature are common responses to severe injury. We have investigated the hypothesis that these responses are due to increases in substrate cycling. A substrate cycle exists when opposing, nonequilibrium reactions catalyzed by different enzymes are operating simultaneously. At least one of the reactions must involve the hydrolysis of ATP. Thus, a substrate cycle both liberates heat and increases energy expenditure, yet there is not net conversion of substrate to product. In studies in volunteers (n = 18) and in patients with severe burns who were in a hypermetabolic state (n = 18), we used stable-isotope tracers to quantify substrate cycling in the pathways of glycolysis and gluconeogenesis and a cycle involving the simultaneous breakdown and synthesis of stored triglyceride (triglyceride-fatty acid cycle). The total rates of triglyceride-fatty acid and glycolytic-gluconeogenic cycling were elevated in the patients by 450 and 250 percent, respectively (P less than 0.01). An infusion of propranolol in the patients greatly reduced triglyceride-fatty acid cycling but did not affect gluconeogenic-glycolytic cycling. We conclude that increased substrate cycling contributes to the increased thermogenesis and energy expenditure following severe burns and that the increased triglyceride-fatty acid cycling is due to beta-adrenergic stimulation.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Triglyceride/fatty acid cycling is involved in the thermogenesis associated with burn injuries, cancer cachexia, and after exercise.
“This cycling is involved in the thermogenesis associated with burn injuries 26, cancer cachexia 27, and after exercise 28.”
From Cellular bioenergetics as a target for obesity therapy (2010) · cites this paper as [26]
Cites
Calculation of substrate oxidation rates in vivo from gaseous exchange.
Frayn, K. N. (1983) · Journal of Applied Physiology · doi:10.1152/jappl.1983.55.2.628 · Cited by 2,365 · see citing works
Wilmore, D. W., LONG, J. M., Mason, A. D., SKREEN, R. W., & Pruitt, B. A. (1974) · Annals of Surgery · doi:10.1097/00000658-197410000-00031 · Cited by 752 · see citing works
Effects of arterial versus venous sampling on analysis of glucose kinetics in man
McGuire, E. A., Helderman, J. H., Tobin, J. D., Andres, R., & Berman, M. D. (1976) · Journal of Applied Physiology · doi:10.1152/jappl.1976.41.4.565 · Cited by 704 · see citing works
Glucose metabolism in severely burned patients
Wolfe, R. R., Durkot, M. J., Allsop, J. R., & Burke, J. F. (1979) · Metabolism · doi:10.1016/0026-0495(79)90007-6 · Cited by 334 · see citing works
Self-citationFutile Cycles in the Metabolism of Glucose
Katz, J. J., & Rognstad, R. (1976) · Current topics in cellular regulation · doi:10.1016/b978-0-12-152810-2.50013-9 · Cited by 324 · see citing works
Control of Glycolysis and Gluconeogenesis in Liver and Kidney Cortex
Newsholme, E. A., & Gevers, W. (1967) · Vitamins and hormones · doi:10.1016/s0083-6729(08)60033-3 · Cited by 224 · see citing works
Tracers in metabolic research: radioisotope and stable isotope/mass spectrometry methods.
Wolfe, R. R. (1984) · PubMed · Cited by 220 · see citing works
Self-citationMetabolic Changes in Burned Patients
Wilmore, D. W., & AULICK, L. H. (1978) · Surgical Clinics of North America · doi:10.1016/s0039-6109(16)41685-3 · Cited by 216 · see citing works
Increased Rates of Whole Body Protein Synthesis and Breakdown in Children Recovering from Burns
Kien, C. L., Young, V. R., Rohrbaugh, D. K., et al. (1978) · Annals of Surgery · doi:10.1097/00000658-197804000-00007 · Cited by 174 · see citing works
Uptake of individual free fatty acids by skeletal muscle and liver in man
Hagenfeldt, L., Wahren, J., Pernow, B., & Räf, L. (1972) · Journal of Clinical Investigation · doi:10.1172/jci107043 · Cited by 170 · see citing works
A Possible Metabolic Basis for the Control of Body Weight
Newsholme, E. A. (1980) · New England Journal of Medicine · doi:10.1056/nejm198002143020711 · Cited by 140 · see citing works
Jahoor, F., Herndon, D. N., & Wolfe, R. R. (1986) · Journal of Clinical Investigation · doi:10.1172/jci112644 · Cited by 123 · see citing works
Self-citationShulman, G. I., Ladenson, P. W., WOLFE, M. H., Ridgway, E. C., & Wolfe, R. R. (1985) · Journal of Clinical Investigation · doi:10.1172/jci112032 · Cited by 102 · see citing works
Self-citationHerndon, D. N., Curreri, P. W., Abston, S., et al. (1987) · Current Problems in Surgery · doi:10.1016/0011-3840(87)90010-4 · Cited by 83 · see citing works
Self-citationMcDonald-Gibson, R. G., & Young, M. (1974) · Clinica Chimica Acta · doi:10.1016/0009-8981(74)90359-3 · Cited by 66 · see citing works
Studies on hepatic glucose cycles in normal and methylprednisolone-treated dogs
Issekutz, B., Jr. (1977) · Metabolism · doi:10.1016/0026-0495(77)90051-8 · Cited by 60 · see citing works
Plasma Palmitate Turnover in Subjects with Thermal Injury
Galster, A. D., Bier, D. M., CRYER, P. E., et al. (1984) · The Journal of Trauma: Injury, Infection, and Critical Care · doi:10.1097/00005373-198411000-00003 · Cited by 52 · see citing works
Brooks, B. J., Arch, J. R. S., & Newsholme, E. A. (1983) · Bioscience Reports · doi:10.1007/bf01122458 · Cited by 51 · see citing works
Hussain, M. N., & Benedict, C. R. (1985) · Clinical Chemistry · doi:10.1093/clinchem/31.11.1861 · Cited by 41 · see citing works
The regulation of plasma ketone body concentration by counterregulatory hormones in man
Schade, D. S., & Eaton, R. P. (1977) · Diabetes · doi:10.2337/diabetes.26.10.989 · Cited by 41 · see citing works
Nonthyroidal control of metabolism after burn injury: Possible role of glucagon
Vaughan, G. M., Becker, R. A., Unger, R. H., Ziegler, M. G., Siler-Khodr, T. M., Pruitt, B. A., & Mason, A. D. (1985) · Metabolism · doi:10.1016/0026-0495(85)90091-5 · Cited by 26 · see citing works
STUDIES ON THE METABOLISM OF FREE FATTY ACIDS IN DIABETIC AND FASTING DOGS*
Spitzer, J. J., & Gold, M. (1965) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1965.tb34792.x · Cited by 24 · see citing works
Cahill, G. F. (1980) · New England Journal of Medicine · doi:10.1056/nejm198002143020708 · Cited by 10 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Intensive insulin therapy in critically ill patients.
Van den Berghe, G., Wouters, P., Weekers, F., Verwaest, C., Bruyninckx, F., Schetz, M., Vlasselaers, D., Ferdinande, P., Lauwers, P., & Bouillon, R. (2001) · New England Journal of Medicine · doi:10.1056/nejmoa011300 · Cited by 9,977 · see citing works
Cellular bioenergetics as a target for obesity therapy
Tseng, Y.-H., Cypess, A. M., & Kahn, C. R. (2010) · Nature Reviews Drug Discovery · doi:10.1038/nrd3138 · Cited by 591 · see citing works
Glyceroneogenesis and the triglyceride/fatty acid cycle
Reshef, L., Olswang, Y., Cassuto, H., Blum, B., Croniger, C. M., Kalhan, S. C., Tilghman, S. M., & Hanson, R. W. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.r300017200 · Cited by 475 · see citing works
Effect of Exercise Intensity, Duration and Mode on Post-Exercise Oxygen Consumption
B??rsheim, E., & Bahr, R. (2003) · Sports Medicine · doi:10.2165/00007256-200333140-00002 · Cited by 466 · see citing works
De Backer, D., Creteur, J., Silva, E., & Vincent, J.-L. (2003) · Critical Care Medicine · doi:10.1097/01.ccm.0000063045.77339.b6 · Cited by 371 · see citing works
Effects of exercise intensity and duration on the excess post-exercise oxygen consumption
Laforgia, J., Withers, R. T., & Gore, C. J. (2006) · Journal of Sports Sciences · doi:10.1080/02640410600552064 · Cited by 282 · see citing works
Optimal protein requirements during the first 2 weeks after the onset of critical illness
Ishibashi, N., Plank, L. D., Sando, K., & Hill, G. L. (1998) · Critical Care Medicine · doi:10.1097/00003246-199809000-00020 · Cited by 245 · see citing works
Metabolic Effects of Caffeine in Humans: Lipid Oxidation or Futile Cycling?
Acheson, K. J., Gremaud, G., Meirim, I., Montigon, F., Krebs, Y., Fay, L. B., Gay, L.-J., Schneiter, P., Schindler, C., & Tappy, L. (2004) · The American Journal of Clinical Nutrition · doi:10.1093/ajcn/79.1.40 · Cited by 239 · see citing works
Abnormal insulin sensitivity persists up to three years in pediatric patients post-burn
Gauglitz, G. G., Herndon, D. N., Kulp, G. A., Meyer, W. J., & Jeschke, M. G. (2009) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2008-1947 · Cited by 186 · see citing works
Self-citationThe metabolic effects of thermal injury
Tredget, E. E., & Yu, Y. M. (1992) · World Journal of Surgery · doi:10.1007/bf02067117 · Cited by 149 · see citing works
Christoffersen, B. Ø., Sanchez‐Delgado, G., John, L. M., Ryan, D. H., Raun, K., & Ravussin, E. (2022) · Obesity · doi:10.1002/oby.23374 · Cited by 142 · see citing works
“is upregulated under several conditions, such as severe burns (107), cachexia (108), and exercise (109), and seems to be primarily mediated by catecholamines (107,108).”
BackgroundHormonal control of substrate cycling in humans.
Miyoshi, H., Shulman, G. I., Peters, E. J., Wolfe, M. H., Elahi, D., & Wolfe, R. R. (1988) · Journal of Clinical Investigation · doi:10.1172/jci113487 · Cited by 139 · see citing works
Self-citationSubstrates for muscle glycogen synthesis in recovery from intense exercise in man
Bangsbo, J., Gollnick, P. D., Graham, T. E., & Saltin, B. (1991) · The Journal of Physiology · doi:10.1113/jphysiol.1991.sp018478 · Cited by 137 · see citing works
Muscle blood flow and oxygen uptake in recovery from exercise
BANGSBO, J., & HELLSTEN, Y. (1998) · Acta Physiologica Scandinavica · doi:10.1046/j.1365-201x.1998.0331e.x · Cited by 118 · see citing works
Triglyceride/fatty acid cycling is increased after exercise
Bahr, R., Hansson, P., & Sejersted, O. M. (1990) · Metabolism · doi:10.1016/0026-0495(90)90313-2 · Cited by 108 · see citing works
Klein, S., & Wolfe, R. R. (1990) · Journal of Clinical Investigation · doi:10.1172/jci114854 · Cited by 82 · see citing works
Self-citationThe 2017 Sir David P Cuthbertson lecture. Amino acids and muscle protein metabolism in critical care
Wolfe, R. R. (2018) · Clinical Nutrition · doi:10.1016/j.clnu.2017.12.010 · Cited by 50 · see citing works
- Authors
- Wolfe, R. R., Herndon, D. N., Jahoor, F., Miyoshi, H., & Wolfe, M.
- Affiliations
- The University of Texas Medical Branch at Galveston (US)
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 1987-08-13
- Volume
- 317
- Issue
- 7
- Pages
- 403-408
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W1999017023
- Cited by
- 467
- References
- 23
- Citations by year
- 2026: 6 · 2025: 7 · 2024: 6 · 2023: 5 · 2022: 2 · 2021: 8 · 2020: 9 · 2019: 8 · 2018: 10 · 2017: 10 · 2016: 8 · 2015: 9 · 2014: 7 · 2013: 10 · 2012: 13
- FWCI
- 15.13
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (DK 33952, DK34817)
- National Center for Research Resources (RR 00073)
- Topics
- Health Sciences › Medicine › Epidemiology › Burn Injury Management and Outcomes
- Health Sciences › Nursing › Nutrition and Dietetics › Clinical Nutrition and Gastroenterology
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Keywords
- severe burns, substrate cycling, hypermetabolism, energy expenditure, thermogenesis, glycolysis, gluconeogenesis, propranolol, beta-adrenergic stimulation, ATP hydrolysis, glucose metabolism, fatty acid metabolism
- MeSH terms
- Adolescent, Adult, Body Temperature Regulation, Burns, Child, Child, Preschool, Energy Metabolism, Fatty Acids, Gluconeogenesis, Glucose, Glycolysis, Humans, Propranolol, Triglycerides
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review