PDF herunterladen
CC BY-NC-ND 4.0 · Int J Sports Med 2022; 43(03): 195-205
DOI: 10.1055/a-1551-9294
Review

The Molecular Signature of High-intensity Training in the Human Body

Patrick Wahl
1   Institute of Cardiovascular Research and Sport Medicine, German Sport University Cologne, Cologne, Germany
2   The German Research Center of Elite Sport Cologne, German Sport University Cologne, Koln, Germany
3   MSH Medical School Hamburg, Institute of Interdisciplinary Exercise Science and Sports Medicine, Hamburg, Germany
,
Wilhelm Bloch
2   The German Research Center of Elite Sport Cologne, German Sport University Cologne, Koln, Germany
4   Molecular and Cellular Sport Medicine, German Sport university, Cologne, Germany
,
Sebastian Proschinger
5   Department for Molecular and Cellular Sports Medicine, Institute for Cardiovascular Research and Sports Medicine, German Sport University Cologne, Cologne, Germany
› Institutsangaben
› Weitere Informationen
Auch verfügbar auf
   Lizenzen und Reprints

Abstract

High-intensity training is becoming increasingly popular outside of elite sport for health prevention and rehabilitation. This expanded application of high-intensity training in different populations requires a deeper understanding of its molecular signature in the human body. Therefore, in this integrative review, cellular and systemic molecular responses to high-intensity training are described for skeletal muscle, cardiovascular system, and the immune system as major effectors and targets of health and performance. Different kinds of stimuli and resulting homeostatic perturbations (i. e., metabolic, mechanical, neuronal, and hormonal) are reflected, taking into account their role in the local and systemic deflection of molecular sensors and mediators, and their role in tissue and organ adaptations. In skeletal muscle, a high metabolic perturbation induced by high-intensity training is the major stimulus for skeletal muscle adaptation. In the cardio-vascular system, high-intensity training induces haemodynamic stress and deflection of the Ca 2+ handling as major stimuli for functional and structural adaptation of the heart and vessels. For the immune system haemodynamic stress, hormones, exosomes, and O2 availability are proposed stimuli that mediate their effects by alteration of different signalling processes leading to local and systemic (anti)inflammatory responses. Overall, high-intensity training shows specific molecular signatures that demonstrate its high potential to improve health and physical performance.

Key words

haemodynamic stress - calcium signalling - metabolic stimuli - skeletal muscle - immune system - cardiovascular system


Publikationsverlauf

Eingereicht: 07. April 2021

Angenommen: 13. Juli 2021

Accepted Manuscript online:
15. Juli 2021

Artikel online veröffentlicht:
12. Oktober 2021

© 2021. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References

  • 1 Ross LM, Porter RR, Durstine JL. High-intensity interval training (HIIT) for patients with chronic diseases. J Sport Health Sci 2016; 5: 139-144
    CrossrefPubMedGoogle Scholar
  • 2 Hoppeler H, Baum O, Lurman G. et al. Molecular mechanisms of muscle plasticity with exercise. Compr Physiol 2011; 1: 1383-1412
    CrossrefPubMedGoogle Scholar
  • 3 Ben-Zeev T, Okun E. High-intensity functional training: Molecular mechanisms and benefits. Neuromolecular Med 2021; 3: 335-338
    PubMed
  • 4 Jiménez-Maldonado A, García-Suárez PC, Rentería I. et al. Impact of high-intensity interval training and sprint interval training on peripheral markers of glycemic control in metabolic syndrome and type 2 diabetes. Biochim Biophys Acta Mol Basis Dis 2020; 1866: 165820
    CrossrefPubMedGoogle Scholar
  • 5 Gibala MJ, Little JP, van Essen M. et al. Short-term sprint interval versus traditional endurance training: Similar initial adaptations in human skeletal muscle and exercise performance. J Physiol 2006; 575: 901-911
    CrossrefPubMedGoogle Scholar
  • 6 Seiler S, Tønnessen E. Intervals, thresholds, and long slow distance: The role of intensity and duration in endurance training. Sportscience 2009; 13: 32-53
    PubMedGoogle Scholar
  • 7 Buchheit M, Laursen PB. High-intensity interval training, solutions to the programming puzzle: Part I: Cardiopulmonary emphasis. Sports Med 2013; 43: 313-338
    CrossrefPubMedGoogle Scholar
  • 8 Yu H, Chen X, Zhu W. et al. A quasi-experimental study of Chinese top-level speed skaters’ training load: Threshold versus polarized model. Int J Sports Physiol Perform 2012; 7: 103-112
    CrossrefPubMedGoogle Scholar
  • 9 Stöggl T, Sperlich B. Polarized training has greater impact on key endurance variables than threshold, high intensity, or high volume training. Front Physiol 2014; 5: 33
    CrossrefPubMedGoogle Scholar
  • 10 Wackerhage H. Molecules ageing and exercise. In: Wackerhage H. (ed) Muscular Exercise Physiology: An Introduction. London: Routledge; 2014
    CrossrefGoogle Scholar
  • 11 Laursen PB. Training for intense exercise performance: High-intensity or high-volume training?. Scand J Med Sci Sports 2010; 20: 1-10
    CrossrefPubMedGoogle Scholar
  • 12 Egan B, Zierath JR. Exercise metabolism and the molecular regulation of skeletal muscle adaptation. Cell Metab 2013; 17: 162-184
    CrossrefPubMedGoogle Scholar
  • 13 O'Neill HM. AMPK and exercise: Glucose uptake and insulin sensitivity. Diabetes Metab J 2013; 37: 1-21
    CrossrefPubMedGoogle Scholar
  • 14 Bae HR, Kim DH, Park MH. et al. β-Hydroxybutyrate suppresses inflammasome formation by ameliorating endoplasmic reticulum stress via AMPK activation. Oncotarget 2016; 7: 66444-66454
    CrossrefPubMedGoogle Scholar
  • 15 Liu JQ, Zhang L, Yao J. et al. AMPK alleviates endoplasmic reticulum stress by inducing the ER-chaperone ORP150 via FOXO1 to protect human bronchial cells from apoptosis. Biochem Biophys Res Commun 2018; 497: 564-570
    CrossrefPubMedGoogle Scholar
  • 16 Dasgupta B, Chhipa RR. Evolving lessons on the complex role of ampk in normal physiology and cancer. Trends Pharmacol Sci 2016; 37: 192-206
    CrossrefPubMedGoogle Scholar
  • 17 Arany Z, Foo S-Y, Ma Y. et al. HIF-independent regulation of VEGF and angiogenesis by the transcriptional coactivator PGC-1alpha. Nature 2008; 451: 1008-1012
    CrossrefPubMedGoogle Scholar
  • 18 Gavin TP, Ruster RS, Carrithers JA. et al. No difference in the skeletal muscle angiogenic response to aerobic exercise training between young and aged men. J Physiol 2007; 585: 231-239
    CrossrefPubMedGoogle Scholar
  • 19 Hoier B, Nordsborg N, Andersen S. et al. Pro-and anti-angiogenic factors in human skeletal muscle in response to acute exercise and training. J Physiol 2012; 590: 595-606
    CrossrefPubMedGoogle Scholar
  • 20 Jensen L, Bangsbo J, Hellsten Y. Effect of high intensity training on capillarization and presence of angiogenic factors in human skeletal muscle. J Physiol 2004; 557: 571-582
    CrossrefPubMedGoogle Scholar
  • 21 Klausen K, Andersen LB, Pelle I. Adaptive changes in work capacity, skeletal muscle capillarization and enzyme levels during training and detraining. Acta Physiol Scand 1981; 113: 9-16
    CrossrefPubMedGoogle Scholar
  • 22 Wackerhage H. Molecular Exercise Physiology: An Introduction. London: Routledge; 2014
    CrossrefGoogle Scholar
  • 23 Popov DV. Adaptation of skeletal muscles to contractile activity of varying duration and intensity: The role of PGC-1α. Biochemistry (Mosc) 2018; 83: 613-628
    CrossrefPubMedGoogle Scholar
  • 24 Gibala M. Molecular responses to high-intensity interval exercise. Appl Physiol Nutr Metab 2009; 34: 428-432
    CrossrefPubMedGoogle Scholar
  • 25 Kupr B, Handschin C. Complex coordination of cell plasticity by a PGC-1α-controlled transcriptional network in skeletal muscle. Front Physiol 2015; 6: 325
    CrossrefPubMedGoogle Scholar
  • 26 Lira VA, Benton CR, Yan Z. et al. PGC-1alpha regulation by exercise training and its influences on muscle function and insulin sensitivity. Am J Physiol Endocrinol Metab 2010; 299: E145-E161
    CrossrefPubMedGoogle Scholar
  • 27 Little JP, Safdar A, Cermak N. et al. Acute endurance exercise increases the nuclear abundance of PGC-1alpha in trained human skeletal muscle. Am J Physiol Regul Integr Comp Physiol 2010; 298: R912-R917
    CrossrefPubMedGoogle Scholar
  • 28 Wright DC, Han D-H, Garcia-Roves PM. et al. Exercise-induced mitochondrial biogenesis begins before the increase in muscle PGC-1alpha expression. J Biol Chem 2007; 282: 194-199
    CrossrefPubMedGoogle Scholar
  • 29 Smith BK, Mukai K, Lally JS. et al. AMP-activated protein kinase is required for exercise-induced peroxisome proliferator-activated receptor co-activator 1 translocation to subsarcolemmal mitochondria in skeletal muscle. J Physiol 2013; 591: 1551-1561
    CrossrefPubMedGoogle Scholar
  • 30 Coccimiglio IF, Clarke DC. ADP is the dominant controller of AMP-activated protein kinase activity dynamics in skeletal muscle during exercise. PLoS Comput Biol 2020; 16: e1008079
    PubMed
  • 31 Egan B, Carson BP, Garcia-Roves PM. et al. Exercise intensity-dependent regulation of peroxisome proliferator-activated receptor coactivator-1 mRNA abundance is associated with differential activation of upstream signalling kinases in human skeletal muscle. J Physiol 2010; 588: 1779-1790
    CrossrefPubMedGoogle Scholar
  • 32 Di Donato DM, West DWD, Churchward-Venne TA. et al. Influence of aerobic exercise intensity on myofibrillar and mitochondrial protein synthesis in young men during early and late postexercise recovery. Am J Physiol Endocrinol Metab 2014; 306: E1025-E1032
    CrossrefPubMedGoogle Scholar
  • 33 Combes A, Dekerle J, Webborn N. et al. Exercise-induced metabolic fluctuations influence AMPK, p38-MAPK and CaMKII phosphorylation in human skeletal muscle. Physiol Rep 2015; 3: e12462
    CrossrefPubMedGoogle Scholar
  • 34 Bartlett JD, Hwa Joo C, Jeong T-S. et al. Matched work high-intensity interval and continuous running induce similar increases in PGC-1α mRNA, AMPK, p38, and p53 phosphorylation in human skeletal muscle. J Appl Physiol 1985 2012: 1135-1143
    PubMedGoogle Scholar
  • 35 Cochran AJR, Percival ME, Tricarico S. et al. Intermittent and continuous high-intensity exercise training induce similar acute but different chronic muscle adaptations. Exp Physiol 2014; 99: 782-791
    CrossrefPubMedGoogle Scholar
  • 36 Gibala MJ, McGee SL, Garnham AP. et al. Brief intense interval exercise activates AMPK and p38 MAPK signaling and increases the expression of PGC-1alpha in human skeletal muscle. J Appl Physiol 1985 2009: 929-934
    PubMedGoogle Scholar
  • 37 Coffey VG, Zhong Z, Shield A. et al. Early signaling responses to divergent exercise stimuli in skeletal muscle from well-trained humans. FASEB J 2006; 20: 190-192
    CrossrefPubMedGoogle Scholar
  • 38 Watt MJ, Southgate RJ, Holmes AG. et al. Suppression of plasma free fatty acids upregulates peroxisome proliferator-activated receptor (PPAR) alpha and delta and PPAR coactivator 1alpha in human skeletal muscle, but not lipid regulatory genes. J Mol Endocrinol 2004; 33: 533-544
    CrossrefPubMedGoogle Scholar
  • 39 Burgomaster KA, Howarth KR, Phillips SM. et al. Similar metabolic adaptations during exercise after low volume sprint interval and traditional endurance training in humans. J Physiol 2008; 586: 151-160
    CrossrefPubMedGoogle Scholar
  • 40 Little JP, Safdar A, Wilkin GP. et al. A practical model of low-volume high-intensity interval training induces mitochondrial biogenesis in human skeletal muscle: Potential mechanisms. J Physiol 2010; 588: 1011-1022
    CrossrefPubMedGoogle Scholar
  • 41 Hennig R, Lømo T. Firing patterns of motor units in normal rats. Nature 1985; 314: 164-166
    CrossrefPubMedGoogle Scholar
  • 42 Lee-Young RS, Canny BJ, Myers DE. et al. AMPK activation is fiber type specific in human skeletal muscle: Effects of exercise and short-term exercise training. J Appl Physiol (1985) 2009; 107: 283-289
    CrossrefPubMedGoogle Scholar
  • 43 Kristensen DE, Albers PH, Prats C. et al. Human muscle fibre type-specific regulation of AMPK and downstream targets by exercise. J Physiol 2015; 593: 2053-2069
    CrossrefPubMedGoogle Scholar
  • 44 Russell AP, Feilchenfeldt J, Schreiber S. et al. Endurance training in humans leads to fiber type-specific increases in levels of peroxisome proliferator-activated receptor-gamma coactivator-1 and peroxisome proliferator-activated receptor-alpha in skeletal muscle. Diabetes 2003; 52: 2874-2881
    CrossrefPubMedGoogle Scholar
  • 45 Kemi OJ, Ellingsen Ø, Ceci M. et al. Aerobic interval training enhances cardiomyocyte contractility and Ca2+cycling by phosphorylation of CaMKII and Thr-17 of phospholamban. J Mol Cell Cardiol 2007; 43: 354-361
    CrossrefPubMedGoogle Scholar
  • 46 Wisløff U, Loennechen JP, Falck G. et al. Increased contractility and calcium sensitivity in cardiac myocytes isolated from endurance trained rats. Cardiovasc Res 2001; 50: 495-508
    CrossrefPubMedGoogle Scholar
  • 47 Stølen TO, Høydal MA, Kemi OJ. et al. Interval training normalizes cardiomyocyte function, diastolic Ca 2+control, and SR Ca2+release synchronicity In a mouse model of diabetic cardiomyopathy. Circ Res 2009; 105: 527-536
    CrossrefPubMedGoogle Scholar
  • 48 Cassidy S, Thoma C, Houghton D. et al. High-intensity interval training: A review of its impact on glucose control and cardiometabolic health. Diabetologia 2017; 60: 7-23
    CrossrefPubMedGoogle Scholar
  • 49 Gunadi JW, Tarawan VM, Setiawan I. et al. Cardiac hypertrophy is stimulated by altered training intensity and correlates with autophagy modulation in male Wistar rats. BMC Sports Sci Med Rehabil 2019; 11: 9
    CrossrefPubMedGoogle Scholar
  • 50 Ghanimati R, Rajabi H, Ramezani F. et al. The effect of preconditioning with high-intensity training on tissue levels of G-CSF, its receptor and C-kit after an acute myocardial infarction in male rats. BMC Cardiovasc Disord 2020; 20: 75
    CrossrefPubMedGoogle Scholar
  • 51 Naderi N, Hemmatinafar M, Gaeini AA. et al. High-intensity interval training increase GATA4, CITED4 and c-Kit and decreases C/EBPβ in rats after myocardial infarction. Life Sci 2019; 221: 319-326
    CrossrefPubMedGoogle Scholar
  • 52 Fallahi A, Gaeini A, Shekarfroush S. et al. Cardioprotective effect of high intensity interval training and nitric oxide metabolites (NO2 − , NO3 − ). Iran J Public Health 2015; 44: 1270-1276
    PubMedGoogle Scholar
  • 53 Novoa U, Arauna D, Moran M. et al. High-intensity exercise reduces cardiac fibrosis and hypertrophy but does not restore the nitroso-redox imbalance in diabetic cardiomyopathy. Oxid Med Cell Longev 2017; 2017: 7921363
    CrossrefPubMedGoogle Scholar
  • 54 Schmitz B, Breulmann FL, Jubran B. et al. A three-step approach identifies novel shear stress-sensitive endothelial microRNAs involved in vasculoprotective effects of high-intensity interval training (HIIT). Oncotarget 2019; 10: 3625-3640
    CrossrefPubMedGoogle Scholar
  • 55 Wahl P, Wehmeier UF, Jansen FJ. et al. Acute effects of different exercise protocols on the circulating vascular microRNAs -16, -21, and -126 in trained subjects. Front Physiol 2016; 7: 643
    CrossrefPubMedGoogle Scholar
  • 56 Wahl P, Jansen F, Achtzehn S. et al. Effects of high intensity training and high volume training on endothelial microparticles and angiogenic growth factors. PLoS One 2014; 9: e96024
    CrossrefPubMedGoogle Scholar
  • 57 Adams V, Reich B, Uhlemann M. et al. Molecular effects of exercise training in patients with cardiovascular disease: Focus on skeletal muscle, endothelium, and myocardium. Am J Physiol Heart Circ Physiol 2017; 313: H72-H88
    CrossrefPubMedGoogle Scholar
  • 58 Schmitz B, Niehues H, Lenders M. et al. Effects of high-intensity interval training on microvascular glycocalyx and associated microRNAs. Am J Physiol Heart Circ Physiol 2019; 316: H1538-H1551
    CrossrefPubMedGoogle Scholar
  • 59 Adams V, Alves M, Fischer T. et al. High-intensity interval training attenuates endothelial dysfunction in a Dahl salt-sensitive rat model of heart failure with preserved ejection fraction. J Appl Physiol (1985) 2015; 119: 745-752
    CrossrefPubMedGoogle Scholar
  • 60 Tsai HH, Lin CP, Lin YH. et al. High-intensity Interval training enhances mobilization/functionality of endothelial progenitor cells and depressed shedding of vascular endothelial cells undergoing hypoxia. Eur J Appl Physiol 2016; 116: 2375-2388
    CrossrefPubMedGoogle Scholar
  • 61 Neufer PD, Bamman MM, Muoio DM. et al. understanding the cellular and molecular mechanisms of physical activity-induced health benefits. Cell Metab 2015; 22: 4-11
    CrossrefPubMedGoogle Scholar
  • 62 Walsh NP, Gleeson MM, Shephard RJ. et al. Institutional Repository Position statement part one : Immune function and exercise. Exerc Immunol Rev 2011; 17: 6-63
    PubMedGoogle Scholar
  • 63 Krüger K, Alack K, Ringseis R. et al. Apoptosis of T-Cell subsets after acute high-intensity interval exercise. Med Sci Sports Exerc 2016; 48: 2021-2029
    CrossrefPubMedGoogle Scholar
  • 64 Wadley AJ, Cullen T, Vautrinot J. et al. High intensity interval exercise increases the frequency of peripheral PD-1 + CD8 + central memory T-cells and soluble PD-L1 in humans. Brain Behav Immun Health 2020; 3: 100049
    CrossrefPubMedGoogle Scholar
  • 65 Postow MA, Callahan MK, Wolchok JD. Immune checkpoint blockade in cancer therapy. J Clin Oncol 2015; 33: 1974-1982
    CrossrefPubMedGoogle Scholar
  • 66 Schenk A, Joisten N, Walzik D. et al. Acute exercise impacts AhR and PD-1 levels of CD8 + T-cells—Exploratory results from a randomized cross-over trial comparing endurance versus resistance exercise. Eur J Appl Physiol 2020; 121: 637-644
    CrossrefPubMedGoogle Scholar
  • 67 Radak Z, Ishihara K, Tekus E. et al. Exercise, oxidants, and antioxidants change the shape of the bell-shaped hormesis curve. Redox Biol 2017; 12: 285-290
    CrossrefPubMedGoogle Scholar
  • 68 Krüger K, Mooren FC. Exercise-induced leukocyte apoptosis. Exerc Immunol Rev 2014; 20: 117-134
    PubMedGoogle Scholar
  • 69 Muri J, Kopf M. Redox regulation of immunometabolism. Nat Rev Immunol 2020; 21: 363-381
    CrossrefPubMedGoogle Scholar
  • 70 Jamurtas AZ, Fatouros IG, Deli CK. et al. The effects of acute low-volume HIIT and aerobic exercise on leukocyte count and redox status. J Sports Sci Med 2018; 17: 501-508
    PubMedGoogle Scholar
  • 71 Fisher G, Schwartz DD, Quindry J. et al. Lymphocyte enzymatic antioxidant responses to oxidative stress following high-intensity interval exercise. J Appl Physiol (1985) 2011; 110: 730-737
    CrossrefPubMedGoogle Scholar
  • 72 De Oliveira Ottone V, Costa KB, Tossige-Gomes R. et al. Late neutrophil priming following a single session of high-intensity interval exercise. Int J Sports Med 2019; 40: 171-179
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 73 Bartlett DB, Shepherd SO, Wilson OJ. et al. Neutrophil and monocyte bactericidal responses to 10 weeks of low-volume high-intensity interval or moderate-intensity continuous training in sedentary adults. Oxid Med Cell Longev 2017; 2017: 8148742
    CrossrefPubMedGoogle Scholar
  • 74 Durrer C, Francois M, Neudorf H. et al. Acute high-intensity interval exercise reduces human monocyte toll-like receptor 2 expression in type 2 diabetes. Am J Physiol Regul Integr Comp Physiol 2017; 312: R529-R538
    CrossrefPubMedGoogle Scholar
  • 75 Robinson E, Durrer C, Simtchouk S. et al. Short-term high-intensity interval and moderate-intensity continuous training reduce leukocyte TLR4 in inactive adults at elevated risk of type 2 diabetes. J Appl Physiol (1985) 2015; 119: 508-516
    CrossrefPubMedGoogle Scholar
  • 76 Joisten N, Proschinger S, Rademacher A. et al. High-intensity interval training reduces neutrophil-to-lymphocyte ratio in persons with multiple sclerosis during inpatient rehabilitation. Mult Scler 2021; 27: 1136–1139
    PubMed
  • 77 Wahl P, Mathes S, Bloch W. et al. Acute impact of recovery on the restoration of cellular immunological homeostasis. Int J Sports Med 2020; 41: 12-20
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 78 Furman D, Campisi J, Verdin E. et al. Chronic inflammation in the etiology of disease across the life span. Nat Med 2019; 25: 1822-1832
    CrossrefPubMedGoogle Scholar
  • 79 Horn A, Van der Meulen JH, Defour A. et al. Mitochondrial redox signaling enables repair of injured skeletal muscle cells. Sci Signal 2017; 10: eaaj1978
    PubMed
  • 80 Schieber M, Chandel NS. ROS function in redox signaling and oxidative stress. Curr Biol 2014; 24: 453-462
    CrossrefPubMedGoogle Scholar
  • 81 Louzada RA, Bouviere J, Matta LP. et al. Redox signaling in widespread health benefits of exercise. Antioxid Redox Signal 2020. Online ahead of print. DOI: 10.1089/ars.2019.7949
    CrossrefPubMed
  • 82 Parker L, Stepto NK, Shaw CS. et al. Acute high-intensity interval exercise-induced redox signaling is associated with enhanced insulin sensitivity in obese middle-aged men. Front Physiol 2016; 7: 411
    CrossrefPubMedGoogle Scholar
  • 83 Bartlett DB, Willis LH, Slentz CA. et al. Ten weeks of high-intensity interval walk training is associated with reduced disease activity and improved innate immune function in older adults with rheumatoid arthritis: A pilot study. Arthritis Res Ther 2018; 20: 127
    CrossrefPubMedGoogle Scholar