Transcriptional regulation of gene expression in human skeletal muscle during recovery from exercise
Abstract
Exercise training elicits a number of adaptive changes in skeletal muscle that result in an improved metabolic efficiency. The molecular mechanisms mediating the cellular adaptations to exercise training in human skeletal muscle are unknown. To test the hypothesis that recovery from exercise is associated with transcriptional activation of specific genes, six untrained male subjects completed 60-90 min of exhaustive one-legged knee extensor exercise for five consecutive days. On day 5, nuclei were isolated from biopsies of the vastus lateralis muscle of the untrained and the trained leg before exercise and from the trained leg immediately after exercise and after 15 min, 1 h, 2 h, and 4 h of recovery. Transcriptional activity of the uncoupling protein 3 (UCP3), pyruvate dehydrogenase kinase 4 (PDK4), and heme oxygenase-1 (HO-1) genes (relative to beta-actin) increased by three- to sevenfold in response to exercise, peaking after 1-2 h of recovery. Increases in mRNA levels followed changes in transcription, peaking between 2 and 4 h after exercise. Lipoprotein lipase and carnitine pamitoyltransferase I gene transcription and mRNA levels showed similar but less dramatic induction patterns, with increases ranging from two- to threefold. In a separate study, a single 4-h bout of cycling exercise (n = 4) elicited from 5 to >20-fold increases in UCP3, PDK4, and HO-1 transcription, suggesting that activation of these genes may be related to the duration or intensity of exercise. These data demonstrate that exercise induces transient increases in transcription of metabolic genes in human skeletal muscle. Moreover, the findings suggest that the cumulative effects of transient increases in transcription during recovery from consecutive bouts of exercise may represent the underlying kinetic basis for the cellular adaptations associated with exercise training.
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?
The recovery period plays a central role in the development of training adaptation.
“The recovery period, which plays a central role in the development of training adaptation [19], is non optimal for prolonging the period of optimized response to the training stimulus [20].”
From Periodization of carbohydrate intake: short-term effect on performance (2016) · cites this paper as [19]
Cites
Single-Step Method of RNA Isolation by Acid Guanidinium Thiocyanate–Phenol–Chloroform Extraction
Chomczynski, P., & Sacchi, N. (1987) · Analytical Biochemistry · doi:10.1006/abio.1987.9999 · Cited by 65,240 · see citing works
Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction
Chomczyński, P., & Sacchi, N. (1987) · Analytical Biochemistry · doi:10.1016/0003-2697(87)90021-2 · Cited by 47,092 · see citing works
Plum, F. (1960) · Archives of Neurology · doi:10.1001/archneur.1960.03840090124020 · Cited by 10,388 · see citing works
Bilirubin Is an Antioxidant of Possible Physiological Importance
Stocker, R., Yamamoto, Y., McDonagh, A. F., Glazer, A. N., & Ames, B. N. (1987) · Science · doi:10.1126/science.3029864 · Cited by 3,502 · see citing works
Skeletal Muscle Adaptability: Significance for Metabolism and Performance
Saltin, B., & Gollnick, P. D. (1983) · Comprehensive physiology · doi:10.1002/cphy.cp100119 · Cited by 917 · see citing works
Handbook of Physiology. Section 12. Exercise: Regulation and Integration of Multiple Systems
Coast, J. R. (1997) · Medicine & Science in Sports & Exercise · doi:10.1097/00005768-199703000-00021 · Cited by 915 · see citing works
Exercise : regulation and integration of multiple systems
Rowell, L. B., & Shepherd, J. T. (1996) · Medical Entomology and Zoology · Cited by 810 · see citing works
Maines, M. D., Trakshel, G. M., & Kutty, R. K. (1986) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)42488-4 · Cited by 759 · see citing works
Gong, D., He, Y., Karas, M., & Reitman, M. L. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.39.24129 · Cited by 740 · see citing works
Waging war on modern chronic diseases: primary prevention through exercise biology
Booth, F. W., Gordon, S. E., Carlson, C. J., & Hamilton, M. T. (2000) · Journal of Applied Physiology · doi:10.1152/jappl.2000.88.2.774 · Cited by 693 · see citing works
Energy metabolism in uncoupling protein 3 gene knockout mice
Vidal-Puig, A. J., Grujic, D., Zhang, C.-Y., Hagen, T., Boss, O., Ido, Y., Szczepanik, A., Wade, J., Mootha, V., Cortright, R., et al. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m910179199 · Cited by 677 · see citing works
Evidence for existence of tissue-specific regulation of the mammalian pyruvate dehydrogenase complex
Bowker-Kinley, M. M., DAVIS, I. W., Wu, P., HARRIS, A. R., & POPOV, M. K. (1998) · Biochemical Journal · doi:10.1042/bj3290191 · Cited by 567 · see citing works
Gimeno, R. E., Dembski, M., Weng, X., Deng, N., Shyjan, A. W., Gimeno, C. J., Iris, F., Ellis, S. J., Woolf, E. A., & Tartaglia, L. A. (1997) · Diabetes · doi:10.2337/diab.46.5.900 · Cited by 496 · see citing works
Transcriptional control of rat heme oxygenase by heat shock.
Shibahara, S., Müller, R., & Taguchi, H. (1987) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)45138-1 · Cited by 415 · see citing works
Gong, D., Monemdjou, S., Gavrilova, O., Leon, L. R., Marcus‐Samuels, B., Chou, C. J., Everett, C. A., Kozak, L. P., Li, C., Deng, C., et al. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m910177199 · Cited by 385 · see citing works
Dynamic knee extension as model for study of isolated exercising muscle in humans
Andersen, P., Adams, R. P., Sjøgaard, G., Thorboe, A., & Saltin, B. (1985) · Journal of Applied Physiology · doi:10.1152/jappl.1985.59.5.1647 · Cited by 385 · see citing works
Wu, P., Sato, J., Zhao, Y., Jaskiewicz, J. A., POPOV, M. K., & HARRIS, A. R. (1998) · Biochemical Journal · doi:10.1042/bj3290197 · Cited by 310 · see citing works
Hemoglobin Provides Protection Against Lethal Endotoxemia in Rats: The Role of Heme Oxygenase-1
Otterbein, L. E., Sylvester, S. L., & Choi, A. M. K. (1995) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/ajrcmb.13.5.7576696 · Cited by 308 · see citing works
Utilization of skeletal muscle triacylglycerol during postexercise recovery in humans
Kiens, B., & Richter, E. A. (1998) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1998.275.2.e332 · Cited by 290 · see citing works
Wu, P., Inskeep, K., Bowker-Kinley, M. M., Popov, K. M., & Harris, R. A. (1999) · Diabetes · doi:10.2337/diabetes.48.8.1593 · Cited by 290 · see citing works
Exercise induces a transient increase in transcription of the GLUT-4 gene in skeletal muscle
Neufer, P. D., & Dohm, G. L. (1993) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.1993.265.6.c1597 · Cited by 192 · see citing works
Maines, M. D., Mayer, R., Ewing, J. F., & McCoubrey, W. K. (1993) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)10290-5 · Cited by 182 · see citing works
Seip, R. L., Mair, K., Cole, T. G., & Semenkovich, C. F. (1997) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1997.272.2.e255 · Cited by 173 · see citing works
Muscle Plasticity: Energy Demand and Supply Processes
Booth, F. W., & Baldwin, K. M. (1996) · Comprehensive physiology · doi:10.1002/cphy.cp120124 · Cited by 165 · see citing works
Effects of exercise on GLUT-4 and glycogenin gene expression in human skeletal muscle
Kraniou, Y. N., Cameron‐Smith, D., Misso, M. L., Collier, G. R., & Hargreaves, M. (2000) · Journal of Applied Physiology · doi:10.1152/jappl.2000.88.2.794 · Cited by 153 · see citing works
Oxidation of urate in human skeletal muscle during exercise
Hellsten, Y., Tullson, P. C., Richter, E. A., & Bangsbo, J. (1997) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(96)00286-9 · Cited by 136 · see citing works
Regulation of Gene Expression in Skeletal Muscle by Contractile Activity
Williams, R. S., & Neufer, P. D. (1996) · Comprehensive physiology · doi:10.1002/cphy.cp120125 · Cited by 132 · see citing works
Role of local contractile activity and muscle fiber type on LPL regulation during exercise
Hamilton, M. T., Etienne, J., McClure, W. C., Pavey, B. S., & Holloway, A. K. (1998) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1998.275.6.e1016 · Cited by 132 · see citing works
Regulating ATP turnover rates over broad dynamic work ranges in skeletal muscles
Hochachka, P. W., & Matheson, G. O. (1992) · Journal of Applied Physiology · doi:10.1152/jappl.1992.73.5.1697 · Cited by 131 · see citing works
Tsuboyama-Kasaoka, N., Tsunoda, N., Maruyama, K., Takahashi, M. M., Kim, H., Ikemoto, S., & Ezaki, O. (1998) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1998.8818 · Cited by 131 · see citing works
Vusse, G. J., & Reneman, R. S. (1996) · Comprehensive physiology · doi:10.1002/cphy.cp120121 · Cited by 128 · see citing works
Murphy, B. J., Laderoute, K. R., Short, S., & Sutherland, R. J. (1991) · British Journal of Cancer · doi:10.1038/bjc.1991.241 · Cited by 125 · see citing works
Rat skeletal muscle hexokinase II mRNA and activity are increased by a single bout of acute exercise
O'Doherty, R. M., Bracy, D. P., Osawa, H., Wasserman, D. H., & Granner, D. K. (1994) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1994.266.2.e171 · Cited by 98 · see citing works
Hildebrandt, A. L., & Neufer, P. D. (2000) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.2000.278.6.e1078 · Cited by 93 · see citing works
Regulation of skeletal muscle UCP-2 and UCP-3 gene expression by exercise and denervation
Cortright, R. N., Zheng, D., Jones, J. P., Fluckey, J. D., DiCarlo, S. E., Grujić, D., Lowell, B. B., & Dohm, G. L. (1999) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1999.276.1.e217 · Cited by 88 · see citing works
Regulation of hexokinase II activity and expression in human muscle by moderate exercise
Koval, J., DeFronzo, R. A., O'Doherty, R. M., Printz, R. L., Ardehali, H., Granner, D. K., & Mandarino, L. J. (1998) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1998.274.2.e304 · Cited by 79 · see citing works
Vesely, M. J. J., Exon, D. J., Clark, J., Foresti, R., Green, C. J., & Motterlini, R. (1998) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.1998.275.4.c1087 · Cited by 79 · see citing works
Induction of heme oxygenase-1 (HSP32) mRNA in skeletal muscle following contractions
Essig, D. A., Borger, D. R., & Jackson, D. A. (1997) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.1997.272.1.c59 · Cited by 77 · see citing works
Recombinant human uncoupling protein‐3 increases thermogenesis in yeast cells
Hinz, W., Faller, B., Grueninger, S., Gazzotti, P., & Chiesi, M. (1999) · FEBS Letters · doi:10.1016/s0014-5793(99)00331-2 · Cited by 68 · see citing works
Neufer, P. D., Ordway, G. A., & Williams, R. S. (1998) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.1998.274.2.c341 · Cited by 68 · see citing works
Darwich, R., & Massarani, B. (2000) · Journal of Applied Physics · doi:10.1063/1.373804 · Cited by 67 · see citing works
Carbohydrate feeding speeds reversal of enhanced glucose uptake in muscle after exercise
Young, J. C., Garthwaite, S. M., Bryan, J. E., Cartier, L.-J., & Holloszy, J. O. (1983) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1983.245.5.r684 · Cited by 50 · see citing works
Regulation of Extramuscular Fuel Sources During Exercise
Wasserman, D. H., & Cherrington, A. D. (1996) · Comprehensive physiology · doi:10.1002/cphy.cp120123 · Cited by 41 · see citing works
How Much Pain for Cardiac Gain?
Barinaga, M. (1997) · Science · doi:10.1126/science.276.5317.1324 · Cited by 30 · see citing works
Heterogeneity of response to exercise of rat muscle pyruvate dehydrogenase complex
Denyer, G. S., Cooney, G. J., Storlien, L. H., Jenkins, A. B., Kraegen, E. W., Kusunoki, M., & Caterson, I. D. (1991) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/bf00372995 · Cited by 21 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Acute Exercise Remodels Promoter Methylation in Human Skeletal Muscle
Barrès, R., Yan, J., Egan, B., Treebak, J. T., Rasmussen, M., Fritz, T., Caidahl, K., Krook, A., O'Gorman, D. J., & Zierath, J. R. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.01.001 · Cited by 965 · see citing works
“Exercise increases the messenger RNA (mRNA) expression and protein levels of a plethora of genes regulating mitochondrial function and fuel usage, including PGC-1a, transcription factor A, mitochondrial (TFAM); peroxisome proliferator-activated receptor d (PPAR-d); and pyruvate dehydrogenase kinase, isoenzyme 4 (PDK4)…”
BackgroundInfluentialDishman, R. K., Berthoud, H., Booth, F. W., Cotman, C. W., Edgerton, V. R., Fleshner, M. R., Gandevia, S. C., Gomez‐Pinilla, F., Greenwood, B. N., Hillman, C. H., et al. (2006) · Obesity · doi:10.1038/oby.2006.46 · Cited by 958 · see citing works
Evidence for a release of brain-derived neurotrophic factor from the brain during exercise
Rasmussen, P., Brassard, P., Adser, H., Pedersen, M. V., Leick, L., Hart, E., Secher, N. H., Pedersen, B. K., & Pilegaard, H. (2009) · Experimental Physiology · doi:10.1113/expphysiol.2009.048512 · Cited by 914 · see citing works
Self-citationExercise induces transient transcriptional activation of the PGC‐1α gene in human skeletal muscle
Pilegaard, H., Saltin, B., & Neufer, P. D. (2003) · The Journal of Physiology · doi:10.1113/jphysiol.2002.034850 · Cited by 885 · see citing works
The Molecular Bases of Training Adaptation
Coffey, V. G., & Hawley, J. A. (2007) · Sports Medicine · doi:10.2165/00007256-200737090-00001 · Cited by 756 · see citing works
Invited Review: Contractile activity-induced mitochondrial biogenesis in skeletal muscle
Hood, D. A. (2001) · Journal of Applied Physiology · doi:10.1152/jappl.2001.90.3.1137 · Cited by 692 · see citing works
Perry, C. G. R., Lally, J., Holloway, G. P., Heigenhauser, G. J. F., Bonen, A., & Spriet, L. L. (2010) · The Journal of Physiology · doi:10.1113/jphysiol.2010.199448 · Cited by 559 · see citing works
Searching for the exercise factor: is IL-6 a candidate?
Pedersen (2003) · Journal of Muscle Research and Cell Motility · doi:10.1023/a:1026070911202 · Cited by 564 · see citing works
The role of FoxO in the regulation of metabolism
Gross, D. N., van den Heuvel, A. P. J., & Birnbaum, M. J. (2008) · Oncogene · doi:10.1038/onc.2008.25 · Cited by 555 · see citing works
Keller, C., Steensberg, A., Pilegaard, H., Osada, T., Saltin, B., Pedersen, B. K., & Neufer, P. D. (2001) · The FASEB Journal · doi:10.1096/fj.01-0507fje · Cited by 514 · see citing works
Endurance training enhances BDNF release from the human brain
Seifert, T., Brassard, P., Wissenberg, M., Rasmussen, P., Nordby, P., Stallknecht, B., Adser, H., Jakobsen, A. H., Pilegaard, H., Nielsen, H. B., et al. (2010) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00525.2009 · Cited by 502 · see citing works
AMPK in skeletal muscle function and metabolism
Kjøbsted, R., Hingst, J. R., Fentz, J., Foretz, M., Sanz, M.-N., Pehmøller, C. K., Shum, M., Marette, A., Mounier, R., Treebak, J. T., et al. (2017) · The FASEB Journal · doi:10.1096/fj.201700442r · Cited by 496 · see citing works
Sympathetic Overstimulation During Critical Illness: Adverse Effects of Adrenergic Stress
Dünser, M. W., & Hasibeder, W. R. (2009) · Journal of Intensive Care Medicine · doi:10.1177/0885066609340519 · Cited by 485 · see citing works
AMPK and the biochemistry of exercise: implications for human health and disease
Richter, E. A., & Ruderman, N. B. (2009) · Biochemical Journal · doi:10.1042/bj20082055 · Cited by 481 · see citing works
Molecular basis of skeletal muscle plasticity-from gene to form and function
Flück, M., & Hoppeler, H. H. (2003) · Reviews of physiology, biochemistry and pharmacology · doi:10.1007/s10254-002-0004-7 · Cited by 476 · see citing works
Understanding the Cellular and Molecular Mechanisms of Physical Activity-Induced Health Benefits
Neufer, P. D., Bamman, M. M., Muoio, D. M., Bouchard, C., Cooper, D. M., Goodpaster, B. H., Booth, F. W., Kohrt, W. M., Gerszten, R. E., Mattson, M. P., et al. (2015) · Cell Metabolism · doi:10.1016/j.cmet.2015.05.011 · Cited by 474 · see citing works
Skeletal Muscle Lipid Metabolism in Exercise and Insulin Resistance
Kiens, B. (2006) · Physiological Reviews · doi:10.1152/physrev.00023.2004 · Cited by 478 · see citing works
Analysis of global mRNA expression in human skeletal muscle during recovery from endurance exercise
Mahoney, D. J., Parise, G., Melov, S., Safdar, A., & Tarnopolsky, M. A. (2005) · The FASEB Journal · doi:10.1096/fj.04-3149fje · Cited by 418 · see citing works
Waging war on physical inactivity: using modern molecular ammunition against an ancient enemy.
Booth, F., Chakravarthy, M., Gordon, S., & Spangenburg, E. (2002) · Journal of applied physiology · doi:10.1152/japplphysiol.00073.2002 · Cited by 467 · see citing works
IL-6 and TNF-α expression in, and release from, contracting human skeletal muscle
Steensberg, A., Keller, C., Starkie, R. L., Osada, T., Febbraio, M. A., & Pedersen, B. K. (2002) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00255.2002 · Cited by 410 · see citing works
Control of the size of the human muscle mass
Rennie, M. J., Wackerhage, H., Spangenburg, E. E., & Booth, F. W. (2004) · Annual Review of Physiology · doi:10.1146/annurev.physiol.66.052102.134444 · Cited by 399 · see citing works
Energy-sensing and signaling by AMP-activated protein kinase in skeletal muscle
Winder, W. W. (2001) · Journal of Applied Physiology · doi:10.1152/jappl.2001.91.3.1017 · Cited by 375 · see citing works
Dressel, U., Allen, T. L., Pippal, J. B., Rohde, P. R., Lau, P., & Muscat, G. E. O. (2003) · Molecular Endocrinology · doi:10.1210/me.2003-0151 · Cited by 370 · see citing works
Coordination of metabolic plasticity in skeletal muscle
Hood, D. A., Irrcher, I., Ljubicic, V., & Joseph, A.-M. (2006) · Journal of Experimental Biology · doi:10.1242/jeb.02182 · Cited by 370 · see citing works
Biological Mechanisms of Physical Activity in Preventing Cognitive Decline
Lista, I., & Sorrentino, G. (2009) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-009-9488-x · Cited by 367 · see citing works
Wende, A. R., Huss, J. M., Schaeffer, P. J., Giguère, V., & Kelly, D. P. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.24.10684-10694.2005 · Cited by 354 · see citing works
Kozakowska, M., Pietraszek‐Gremplewicz, K., Józkowicz, A., & Dulak, J. (2015) · Journal of Muscle Research and Cell Motility · doi:10.1007/s10974-015-9438-9 · Cited by 332 · see citing works
Periodized Nutrition for Athletes
Jeukendrup, A. E. (2017) · Sports Medicine · doi:10.1007/s40279-017-0694-2 · Cited by 299 · see citing works
Flück, M. (2006) · Journal of Experimental Biology · doi:10.1242/jeb.02149 · Cited by 303 · see citing works
Exercise training increases lipid metabolism gene expression in human skeletal muscle
Tunstall, R. J., Mehan, K. A., Wadley, G. D., Collier, G. R., Bonen, A., Hargreaves, M., & Cameron-Smith, D. (2002) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00475.2001 · Cited by 292 · see citing works
Regulation of muscle GLUT-4 transcription by AMP-activated protein kinase
Zheng, D., MacLean, P. S., Pohnert, S. C., Knight, J. B., Olson, A. L., Winder, W. W., & Dohm, G. L. (2001) · Journal of Applied Physiology · doi:10.1152/jappl.2001.91.3.1073 · Cited by 292 · see citing works
Yang, Y., Creer, A., Jemiolo, B., & Trappe, S. (2005) · Journal of Applied Physiology · doi:10.1152/japplphysiol.01185.2004 · Cited by 290 · see citing works
Physiological activation of hypoxia inducible factor‐1 in human skeletal muscle
Ameln, H., Gustafsson, T., Sundberg, C. J., Okamoto, K., Jansson, E., Poellinger, L., & Makino, Y. (2005) · The FASEB Journal · doi:10.1096/fj.04-2304fje · Cited by 276 · see citing works
Exercise and gene expression: physiological regulation of the human genome through physical activity
Booth, F. W., Chakravarthy, M. V., & Spangenburg, E. E. (2002) · The Journal of Physiology · doi:10.1113/jphysiol.2002.019265 · Cited by 277 · see citing works
Effects of α‐AMPK knockout on exercise‐induced gene activation in mouse skeletal muscle
Jørgensen, S. B., Wojtaszewski, J. F. P., Viollet, B., Andreelli, F., Birk, J. B., Hellsten, Y., Schjerling, P., Vaulont, S., Neufer, P. D., Richter, E. A., et al. (2005) · The FASEB Journal · doi:10.1096/fj.04-3144fje · Cited by 274 · see citing works
Egan, B., & Sharples, A. P. (2023) · Physiological Reviews · doi:10.1152/physrev.00054.2021 · Cited by 278 · see citing works
Nielsen, A. R., Mounier, R., Plomgaard, P., Mortensen, O. H., Penkowa, M., Speerschneider, T., Pilegaard, H., & Pedersen, B. K. (2007) · The Journal of Physiology · doi:10.1113/jphysiol.2007.139618 · Cited by 266 · see citing works
Roche, T. E., & Hiromasa, Y. (2007) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-007-6380-z · Cited by 265 · see citing works
NCoR1 Is a Conserved Physiological Modulator of Muscle Mass and Oxidative Function
Yamamoto, H., Williams, E. G., Mouchiroud, L., Cantó, C., Fan, W., Downes, M., Héligon, C., Barish, G. D., Desvergne, B., Evans, R. M., et al. (2011) · Cell · doi:10.1016/j.cell.2011.10.017 · Cited by 261 · see citing works
Time- and exercise-dependent gene regulation in human skeletal muscle
Zambon, A. C., McDearmon, E. L., Salomonis, N., Vranizan, K. M., Johansen, K. L., Adey, D., Takahashi, J. S., Schambelan, M., & Conklin, B. R. (2003) · Genome Biology · doi:10.1186/gb-2003-4-10-r61 · Cited by 254 · see citing works
Invited Review: Uncoupling proteins and thermoregulation
Argyropoulos, G., & Harper, M. (2002) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00994.2001 · Cited by 231 · see citing works
Cancer–related fatigue: can exercise physiology assist oncologists?
Lucía, A., Earnest, C. P., & Pérez, M. (2003) · The Lancet Oncology · doi:10.1016/s1470-2045(03)01221-x · Cited by 248 · see citing works
Huang, B., Wu, P., Bowker-Kinley, M. M., & Harris, R. A. (2002) · Diabetes · doi:10.2337/diabetes.51.2.276 · Cited by 246 · see citing works
PGC-1α-mediated adaptations in skeletal muscle
Olesen, J., Kiilerich, K., & Pilegaard, H. (2010) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-010-0834-0 · Cited by 244 · see citing works
Cameron-Smith, D., Burke, L. M., Angus, D. J., Tunstall, R. J., Cox, G. R., Bonen, A., Hawley, J. A., & Hargreaves, M. (2003) · The American Journal of Clinical Nutrition · doi:10.1093/ajcn/77.2.313 · Cited by 243 · see citing works
Safdar, A., Abadi, A., Akhtar, M., Hettinga, B. P., & Tarnopolsky, M. A. (2009) · PLoS ONE · doi:10.1371/journal.pone.0005610 · Cited by 238 · see citing works
Leick, L., Wojtaszewski, J. F. P., Johansen, S. T., Kiilerich, K., Comes, G., Hellsten, Y., Hidalgo, J., & Pilegaard, H. (2007) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00666.2007 · Cited by 236 · see citing works
Pilegaard, H., Keller, C., Steensberg, A., Wulff Helge, J., Klarlund Pedersen, B., Saltin, B., & Neufer, P. D. (2002) · The Journal of Physiology · doi:10.1113/jphysiol.2002.016832 · Cited by 234 · see citing works
Zoll, J., Ponsot, E., Dufour, S. P., Doutreleau, S., Ventura‐Clapier, R., Vogt, M., Hoppeler, H. H., Richard, R., & Flück, M. (2006) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00359.2005 · Cited by 232 · see citing works
Plasticity of skeletal muscle mitochondria: structure and function.
HOPPELER, H., & FL??CK, M. (2003) · Medicine & Science in Sports & Exercise · doi:10.1097/00005768-200301000-00016 · Cited by 267 · see citing works
Muoio, D. M., Way, J. M., Tanner, C. J., Winegar, D. A., Kliewer, S. A., Houmard, J. A., Kraus, W. E., & Dohm, G. L. (2002) · Diabetes · doi:10.2337/diabetes.51.4.901 · Cited by 226 · see citing works
Knudsen, J. G., Murholm, M., Carey, A. L., Biensø, R., Basse, A., Allen, T., Hidalgo, J., Kingwell, B., Febbraio, M., Hansen, J., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0084910 · Cited by 202 · see citing works
Antioxidant supplements and endurance exercise: Current evidence and mechanistic insights
Mason, S. A., Trewin, A. J., Parker, L., & Wadley, G. D. (2020) · Redox Biology · doi:10.1016/j.redox.2020.101471 · Cited by 226 · see citing works
Exercise adaptations: molecular mechanisms and potential targets for therapeutic benefit
McGee, S. L., & Hargreaves, M. (2020) · Nature Reviews Endocrinology · doi:10.1038/s41574-020-0377-1 · Cited by 221 · see citing works
Wu, P., Peters, J. M., & Harris, R. A. (2001) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.2001.5608 · Cited by 206 · see citing works
UCP2 and UCP3 in muscle controlling body metabolism
Schrauwen, P., & Hesselink, M. K. C. (2002) · Journal of Experimental Biology · doi:10.1242/jeb.205.15.2275 · Cited by 205 · see citing works
Hawley, J. A. (2009) · Applied Physiology Nutrition and Metabolism · doi:10.1139/h09-023 · Cited by 203 · see citing works
Watt, M. J., Heigenhauser, G. J. F., Dyck, D. J., & Spriet, L. L. (2002) · The Journal of Physiology · doi:10.1113/jphysiol.2002.018820 · Cited by 201 · see citing works
Sprecher, D. L., Massien, C., Pearce, G., Billin, A. N., Perlstein, I., Willson, T. M., Hassall, D. G., Ancellin, N., Patterson, S. D., Lobe, D. C., et al. (2006) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.0000252790.70572.0c · Cited by 200 · see citing works
Jørgensen, S. B., Treebak, J. T., Viollet, B., Schjerling, P., Vaulont, S., Wojtaszewski, J. F. P., & Richter, E. A. (2006) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00243.2006 · Cited by 176 · see citing works
Resistance exercise alters MRF and IGF-I mRNA content in human skeletal muscle
Psilander, N., Damsgaard, R., & Pilegaard, H. (2003) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00903.2002 · Cited by 178 · see citing works
Lundby, C., Nordsborg, N. B., Kusuhara, K., Kristensen, K. M., Neufer, P. D., & Pilegaard, H. (2005) · European Journal of Applied Physiology · doi:10.1007/s00421-005-0022-7 · Cited by 173 · see citing works
Blood Flow Restriction Enhances Post–Resistance Exercise Angiogenic Gene Expression
Larkin-Kaiser, K. A., MacNeil, R. G., Dirain, M. L. S., SANDESARA, B., Manini, T. M., & Buford, T. W. (2012) · Medicine & Science in Sports & Exercise · doi:10.1249/mss.0b013e3182625928 · Cited by 173 · see citing works
SCHRAUWEN, P., SARIS, W. H. M., & HESSELINK, M. K. C. (2001) · The FASEB Journal · doi:10.1096/fj.01-0400hyp · Cited by 172 · see citing works
Wojtaszewski, J. F. P., Birk, J. B., Frøsig, C., Holten, M., Pilegaard, H., & Dela, F. (2005) · The Journal of Physiology · doi:10.1113/jphysiol.2005.082669 · Cited by 170 · see citing works
Nikolić, N., Bakke, S. S., Kase, E. T., Rudberg, I., Halle, I. F., Rustan, A. C., Thoresen, G. H., & Aas, V. (2012) · PLoS ONE · doi:10.1371/journal.pone.0033203 · Cited by 164 · see citing works
Ljubicic, V., Joseph, A.-M., Saleem, A., Uguccioni, G., Collu-Marchese, M., Lai, R. Y. J., Nguyen, L. M.-D., & Hood, D. A. (2010) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2009.07.031 · Cited by 167 · see citing works
Fischer, C. P., Plomgaard, P., Hansen, A. K., Pilegaard, H., Saltin, B., & Pedersen, B. K. (2004) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00206.2004 · Cited by 165 · see citing works
Self-citationHeat shock proteins and exercise: a primer
Noble, E. G., Milne, K. J., & Melling, C. W. J. (2008) · Applied Physiology Nutrition and Metabolism · doi:10.1139/h08-069 · Cited by 165 · see citing works
Rapid exercise-induced changes in PGC-1α mRNA and protein in human skeletal muscle
Mathai, A. S., Bonen, A., Benton, C. R., Robinson, D. L., & Graham, T. E. (2008) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00847.2007 · Cited by 158 · see citing works
Chen, Y., Nader, G. A., Baar, K. R., Fedele, M. J., Hoffman, E. P., & Esser, K. A. (2002) · The Journal of Physiology · doi:10.1113/jphysiol.2002.021220 · Cited by 158 · see citing works
Pro‐ and anti‐angiogenic factors in human skeletal muscle in response to acute exercise and training
Høier, B., Nordsborg, N. B., Andersen, S., Jensen, L., Nybo, L., Bangsbo, J., & Hellsten, Y. (2011) · The Journal of Physiology · doi:10.1113/jphysiol.2011.216135 · Cited by 158 · see citing works
Pilegaard, H., Saltin, B., & Neufer, P. D. (2003) · Diabetes · doi:10.2337/diabetes.52.3.657 · Cited by 157 · see citing works
Interleukin‐6 production in human subcutaneous abdominal adipose tissue: the effect of exercise
Lyngsø, D., Simonsen, L., & Bülow, J. (2002) · The Journal of Physiology · doi:10.1113/jphysiol.2002.019380 · Cited by 155 · see citing works
Pilegaard, H., Osada, T., Andersen, L. T., Helge, J. W., Saltin, B., & Neufer, P. D. (2005) · Metabolism · doi:10.1016/j.metabol.2005.03.008 · Cited by 154 · see citing works
Self-citationLIF is a contraction-induced myokine stimulating human myocyte proliferation
Broholm, C., Laye, M. J., Brandt, C., Vadalasetty, R., Pilegaard, H., Pedersen, B. K., & Scheele, C. C. (2011) · Journal of Applied Physiology · doi:10.1152/japplphysiol.01399.2010 · Cited by 155 · see citing works
Creer, A., Gallagher, P., Slivka, D., Jemiolo, B., Fink, W., & Trappe, S. (2005) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00110.2005 · Cited by 150 · see citing works
Response and adaptation of skeletal muscle to exercise - the role of reactive oxygen species
Niess, A. M. (2007) · Frontiers in bioscience · doi:10.2741/2431 · Cited by 146 · see citing works
Promoting training adaptations through nutritional interventions
Hawley, J. A., Tipton, K. D., & Millard-Stafford, M. L. (2006) · Journal of Sports Sciences · doi:10.1080/02640410500482727 · Cited by 149 · see citing works
Nielsen, J., Mustard, K. J., Graham, D. A., Yu, H.-Y., MacDonald, C. S., Pilegaard, H., Goodyear, L., Hardie, D. G., Richter, E., & Wojtaszewski, J. (2003) · Journal of applied physiology · doi:10.1152/japplphysiol.00642.2002 · Cited by 160 · see citing works
Effects of acute and chronic endurance exercise on mitochondrial uncoupling in human skeletal muscle
Fernström, M., Tonkonogi, M., & Sahlin, K. (2003) · The Journal of Physiology · doi:10.1113/jphysiol.2003.055202 · Cited by 148 · see citing works
De Bock, K., Richter, E. A., Russell, A. P., Eijnde, B. O., Derave, W., Ramaekers, M., Koninckx, E., Léger, B., Verhaeghe, J., & Hespel, P. (2005) · The Journal of Physiology · doi:10.1113/jphysiol.2005.083170 · Cited by 145 · see citing works
Watt, M. J., Southgate, R. J., Holmes, A. G., & Febbraio, M. A. (2004) · Journal of Molecular Endocrinology · doi:10.1677/jme.1.01499 · Cited by 144 · see citing works
Kiens, B., Roepstorff, C., Glatz, J. F. C., Bonen, A., Schjerling, P., Knudsen, J., & Nielsen, J. N. (2004) · Journal of Applied Physiology · doi:10.1152/japplphysiol.01278.2003 · Cited by 143 · see citing works
McArdle, F., Spiers, S., Aldemir, H., Vasilaki, A., Beaver, A., Iwanejko, L., McArdle, A., & Jackson, M. J. (2004) · The Journal of Physiology · doi:10.1113/jphysiol.2004.069914 · Cited by 139 · see citing works
Coffey, V. G., SHIELD, A. J., Canny, B. J., Carey, K. A., Cameron‐Smith, D., & Hawley, J. A. (2005) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00299.2005 · Cited by 144 · see citing works
Breen, L., Philp, A., Witard, O. C., Jackman, S. R., Selby, A., Smith, K., Baar, K., & Tipton, K. D. (2011) · The Journal of Physiology · doi:10.1113/jphysiol.2011.211888 · Cited by 143 · see citing works
Robach, P., Cairo, G., Gelfi, C., Bernuzzi, F., Pilegaard, H., Viganò, A., Santambrogio, P., Cerretelli, P., Calbet, J. A. L., Moutereau, S., et al. (2007) · Blood · doi:10.1182/blood-2006-08-040006 · Cited by 141 · see citing works
McGlory, C., Devries, M. C., & Phillips, S. M. (2017) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00613.2016 · Cited by 135 · see citing works
Adipose triglyceride lipase in human skeletal muscle is upregulated by exercise training
Alsted, T. J., Nybo, L., Schweiger, M., Fledelius, C., Jacobsen, P., Zimmermann, R., Zechner, R., & Kiens, B. (2008) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.90912.2008 · Cited by 135 · see citing works
Interleukin-6 production by contracting human skeletal muscle: autocrine regulation by IL-6
Keller, P., Keller, C., Carey, A. L., Jauffred, S., Fischer, C. P., Steensberg, A., & Pedersen, B. K. (2003) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2003.09.048 · Cited by 135 · see citing works
Roth, S. M., Ferrell, R. E., Peters, D. G., Metter, E. J., Hurley, B. F., & Rogers, M. A. (2002) · Physiological Genomics · doi:10.1152/physiolgenomics.00028.2002 · Cited by 134 · see citing works
Enhanced Endurance Performance by Periodization of Carbohydrate Intake: “Sleep Low” Strategy
MARQUET, L.-A., BRISSWALTER, J., LOUIS, J., TIOLLIER, E., BURKE, L. M., HAWLEY, J. A., & HAUSSWIRTH, C. (2016) · Medicine & Science in Sports & Exercise · doi:10.1249/mss.0000000000000823 · Cited by 134 · see citing works
Fiorenza, M., Gunnarsson, T. P., Hostrup, M., Iaia, F. M., Schena, F. F., Pilegaard, H., & Bangsbo, J. (2018) · The Journal of Physiology · doi:10.1113/jp275972 · Cited by 132 · see citing works
Pilegaard, H., & Neufer, P. D. (2004) · Proceedings of The Nutrition Society · doi:10.1079/pns2004345 · Cited by 133 · see citing works
Marques‐Aleixo, I., Oliveira, P. J., Moreira, P. I., Magalhães, J., & Ascensão, A. A. M. R. (2012) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2012.08.002 · Cited by 132 · see citing works
Brown Adipose Tissue Growth and Development
Symonds, M. E. (2013) · Scientifica · doi:10.1155/2013/305763 · Cited by 133 · see citing works
Perry, C. G. R., & Hawley, J. A. (2018) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a029686 · Cited by 130 · see citing works
Sailani, M. R., Halling, J. F., Møller, H. D., Lee, H., Plomgaard, P., Pilegaard, H., Snyder, M. P., & Regenberg, B. (2019) · Scientific Reports · doi:10.1038/s41598-018-37895-8 · Cited by 129 · see citing works
Ringholm, S., Biensø, R. S., Kiilerich, K., Guadalupe‐Grau, A., Aachmann‐Andersen, N. J., Saltin, B., Plomgaard, P., Lundby, C., Wojtaszewski, J. F. P., Calbet, J. A. L., et al. (2011) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00230.2011 · Cited by 130 · see citing works
- Authors
- Pilegaard, H., Ordway, G. A., Saltin, B., & Neufer, P. D.
- Affiliations
- University of Copenhagen (DK)
- The University of Texas Southwestern Medical Center (US)
- Yale University (US)
- Venue
- American Journal of Physiology-Endocrinology and Metabolism
- Publisher
- American Physiological Society
- Published
- 2000-10-01
- Volume
- 279
- Issue
- 4
- Pages
- E806-E814
- ISSN
- 0193-1849 (ISSN-L)
- 1522-1555
- OpenAlex
- W2156516623
- Cited by
- 563
- References
- 45
- Citations by year
- 2026: 8 · 2025: 7 · 2024: 15 · 2023: 5 · 2022: 10 · 2021: 18 · 2020: 17 · 2019: 13 · 2018: 20 · 2017: 25 · 2016: 22 · 2015: 29 · 2014: 19 · 2013: 32 · 2012: 26
- FWCI
- 54.07
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Physiology-Endocrinology and Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Funders
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR-45372, R01AR045372)
- Topics
- Health Sciences › Medicine › Complementary and alternative medicine › Cardiovascular and exercise physiology
- Health Sciences › Medicine › Rehabilitation › Exercise and Physiological Responses
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Keywords
- post-exercise recovery, skeletal muscle, gene transcription, training effects, UCP3, PDK4, heme oxygenase-1, lipoprotein lipase, carnitine palmitoyltransferase 1, vastus lateralis, exercise intensity and duration, metabolic gene expression
- MeSH terms
- Uncoupling Protein 3, Actins, Adult, Carnitine O-Palmitoyltransferase, Carrier Proteins, Exercise Test, Physical Exertion, Gene Expression Regulation, Glycogen Synthase, Heme Oxygenase (Decyclizing), Hexokinase, Humans, Ion Channels, Isoenzymes, Leg, Lipoprotein Lipase, Male, Membrane Proteins, Protein Kinases, Rest, RNA, Messenger, Transcription, Genetic, Muscle, Skeletal, Mitochondrial Proteins, Heme Oxygenase-1
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