Resistance Training Improves Hypertrophic and Mitochondrial Adaptation in Skeletal Muscle

Abstract

Resistance training is employed for pursuing muscle strength characterized by activation of mammalian target of rapamycin (mTOR)-mediated hypertrophic signaling for protein production. Endurance training elevates peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) signaling of mitochondrial adaptations for oxidative phosphorylation. Now, emerging evidence suggests that, like endurance training, resistance training also elicits profound effects on mitochondrial adaptations in skeletal muscle, which means that resistance training yields both strength and endurance phenotypes in myofibers, which has treatment value for the muscle loss and poor aerobic capacity in humans. Our review outlines a brief overview of muscle hypertrophic signals with resistance training, and focuses on the effects of resistance training on mitochondrial biogenesis and respiration in skeletal muscle. This study provides novel insights into the therapeutic strategy of resistance training for the metabolically dysfunctional individuals with declined mitochondrial function.

Key words

resistance training - skeletal muscle - mitochondria - metabolic disease

Publication History

Received: 12 July 2022

Accepted: 20 March 2023

Accepted Manuscript online:
21 March 2023

Article published online:
30 May 2023

• References

• 1 Memme JM, Erlich AT, Phukan G. et al. Exercise and mitochondrial health. J Physiol 2019; 599: 803-817
• 2 Nitzsche N, Lenz JC, Voronoi P. et al. Adaption of maximal glycolysis rate after resistance exercise with different volume load. Sports Med Int Open 2020; 4: E39-E44
• 3 Westcott WL. Resistance training is medicine: effects of strength training on health. Curr Sports Med Rep 2012; 11: 209-216
• 4 Barajas-Galindo DE, Gonzalez Arnaiz E, Ferrero Vicente P. et al. Effects of physical exercise in sarcopenia. A systematic review. Endocrinol Diabetes Nutr (Engl Ed.) 2021; 68: 159-169
• 5 Gordon BA, Benson AC, Bird SR. et al. Resistance training improves metabolic health in type 2 diabetes: A systematic review. Diabetes Res Clin Pract 2009; 83: 157-175
• 6 Reljic D, Herrmann HJ, Neurath MF. et al. Iron beats electricity: resistance training but not whole-body electromyostimulation improves cardiometabolic health in obese metabolic syndrome patients during caloric restriction-a randomized-controlled study. Nutrients 2021; 13: 1640
• 7 Stanghelle B, Bentzen H, Giangregorio L. et al. Effects of a resistance and balance exercise programme on physical fitness, health-related quality of life and fear of falling in older women with osteoporosis and vertebral fracture: a randomized controlled trial. Osteoporos Int 2020; 31: 1069-1078
• 8 Westcott WL, Winett RA, Annesi JJ. et al. Prescribing physical activity: Applying the ACSM protocols for exercise type, intensity, and duration across 3 training frequencies. Phys Sportsmed 2009; 37: 51-58
• 9 Atherton PJ, Babraj J, Smith K. et al. Selective activation of AMPK-PGC-1alpha or PKB-TSC2-mTOR signaling can explain specific adaptive responses to endurance or resistance training-like electrical muscle stimulation. FASEB J 2005; 19: 786-788
• 10 Schlegel A, Stainier DY. Lessons from "lower" organisms: what worms, flies, and zebrafish can teach us about human energy metabolism. PLoS Genet 2007; 3: e199
• 11 Vissing K, McGee S, Farup J. et al. Differentiated mTOR but not AMPK signaling after strength vs. endurance exercise in training-accustomed individuals. Scand J Med Sci Sports 2013; 23: 355-366
• 12 Hawley JA, Hargreaves M, Joyner MJ. et al. Integrative biology of exercise. Cell 2014; 159: 738-749
• 13 Solsona R, Pavlin L, Bernardi H. et al. Molecular regulation of skeletal muscle growth and organelle biosynthesis: practical recommendations for exercise training. Int J Mol Sci 2021; 22: 2741
• 14 Drummond MJ, Fry CS, Glynn EL. et al. Rapamycin administration in humans blocks the contraction-induced increase in skeletal muscle protein synthesis. J Physiol 2009; 587: 1535-1546
• 15 Goodman CA. Role of mTORC1 in mechanically induced increases in translation and skeletal muscle mass. J Appl Physiol (1985) 2019; 127: 581-590
• 16 Bodine SC, Stitt TN, Gonzalez M. et al. Akt/mTOR pathway is a crucial regulator of skeletal muscle hypertrophy and can prevent muscle atrophy in vivo. Nat Cell Biol 2001; 3: 1014-1019
• 17 Pallafacchina G, Calabria E, Serrano AL. et al. A protein kinase B-dependent and rapamycin-sensitive pathway controls skeletal muscle growth but not fiber type specification. Proc Natl Acad Sci U S A 2002; 99: 9213-9218
• 18 Bentzinger CF, Lin S, Romanino K. et al. Differential response of skeletal muscles to mTORC1 signaling during atrophy and hypertrophy. Skelet Muscle 2013; 3: 6
• 19 Bentzinger CF, Romanino K, Cloetta D. et al. Skeletal muscle-specific ablation of raptor, but not of rictor, causes metabolic changes and results in muscle dystrophy. Cell Metab 2008; 8: 411-424
• 20 D'Lugos AC, Patel SH, Ormsby JC. et al. Prior acetaminophen consumption impacts the early adaptive cellular response of human skeletal muscle to resistance exercise. J Appl Physiol (1985) 2018; 124: 1012-1024
• 21 Stuart CA, Lee ML, South MA. et al. Muscle hypertrophy in prediabetic men after 16 wk of resistance training. J Appl Physiol (1985) 2017; 123: 894-901
• 22 Lim CH, Luu TS, Phoung LQ. et al. Satellite cell activation and mTOR signaling pathway response to resistance and combined exercise in elite weight lifters. Eur J Appl Physiol 2017; 117: 2355-2363
• 23 Schiaffino S, Reggiani C, Akimoto T. et al. Molecular mechanisms of skeletal muscle hypertrophy. J Neuromuscul Dis 2021; 8: 169-183
• 24 Yoshida T, Delafontaine P. Mechanisms of IGF-1-mediated regulation of skeletal muscle hypertrophy and atrophy. Cells 2020; 9: 1970
• 25 Miyazaki M, Moriya N, Takemasa T. Transient activation of mTORC1 signaling in skeletal muscle is independent of Akt1 regulation. Physiol Rep 2020; 8: e14599
• 26 Miyazaki M, McCarthy JJ, Fedele MJ. et al. Early activation of mTORC1 signalling in response to mechanical overload is independent of phosphoinositide 3-kinase/Akt signalling. J Physiol 2011; 589: 1831-1846
• 27 You JS, Lincoln HC, Kim CR. et al. The role of diacylglycerol kinase zeta and phosphatidic acid in the mechanical activation of mammalian target of rapamycin (mTOR) signaling and skeletal muscle hypertrophy. J Biol Chem 2014; 289: 1551-1563
• 28 You JS, Dooley MS, Kim CR. et al. A DGKzeta-FoxO-ubiquitin proteolytic axis controls fiber size during skeletal muscle remodeling. Sci Signal 2018; 11: eaao6847
• 29 Ruas JL, White JP, Rao RR. et al. A PGC-1alpha isoform induced by resistance training regulates skeletal muscle hypertrophy. Cell 2012; 151: 1319-1331
• 30 Csibi A, Cornille K, Leibovitch MP. et al. The translation regulatory subunit eIF3f controls the kinase-dependent mTOR signaling required for muscle differentiation and hypertrophy in mouse. PLoS One 2010; 5: e8994
• 31 Foster KG, Fingar DC. Mammalian target of rapamycin (mTOR): Conducting the cellular signaling symphony. J Biol Chem 2010; 285: 14071-14077
• 32 Ochi E, Ishii N, Nakazato K. Time course change of IGF1/Akt/mTOR/p70s6k pathway activation in rat gastrocnemius muscle during repeated bouts of eccentric exercise. J Sports Sci Med 2010; 9: 170-175
• 33 Moberg M, Apro W, Ekblom B. et al. Activation of mTORC1 by leucine is potentiated by branched-chain amino acids and even more so by essential amino acids following resistance exercise. Am J Physiol Cell Physiol 2016; 310: C874-C884
• 34 Hannan KM, Brandenburger Y, Jenkins A. et al. mTOR-dependent regulation of ribosomal gene transcription requires S6K1 and is mediated by phosphorylation of the carboxy-terminal activation domain of the nucleolar transcription factor UBF. Mol Cell Biol 2003; 23: 8862-8877
• 35 Crameri RM, Langberg H, Magnusson P. et al. Changes in satellite cells in human skeletal muscle after a single bout of high intensity exercise. J Physiol 2004; 558: 333-340
• 36 Dreyer HC, Blanco CE, Sattler FR. et al. Satellite cell numbers in young and older men 24 hours after eccentric exercise. Muscle Nerve 2006; 33: 242-253
• 37 Masschelein E, D'Hulst G, Zvick J. et al. Exercise promotes satellite cell contribution to myofibers in a load-dependent manner. Skelet Muscle 2020; 10: 21
• 38 Luk HY, Levitt DE, Boyett JC. et al. Resistance exercise-induced hormonal response promotes satellite cell proliferation in untrained men but not in women. Am J Physiol Endocrinol Metab 2019; 317: E421-E432
• 39 Snijders T, Nederveen JP, Bell KE. et al. Prolonged exercise training improves the acute type II muscle fibre satellite cell response in healthy older men. J Physiol 2019; 597: 105-119
• 40 Goh Q, Song T, Petrany MJ. et al. Myonuclear accretion is a determinant of exercise-induced remodeling in skeletal muscle. Elife 2019; 8: 44876
• 41 Murach KA, White SH, Wen Y. et al. Differential requirement for satellite cells during overload-induced muscle hypertrophy in growing versus mature mice. Skelet Muscle 2017; 7: 14
• 42 McCarthy JJ, Mula J, Miyazaki M. et al. Effective fiber hypertrophy in satellite cell-depleted skeletal muscle. Development 2011; 138: 3657-3666
• 43 Bachman JF, Klose A, Liu W. et al. Prepubertal skeletal muscle growth requires Pax7-expressing satellite cell-derived myonuclear contribution. Development 2018; 145: 167197
• 44 Halling JF, Pilegaard H. PGC-1alpha-mediated regulation of mitochondrial function and physiological implications. Appl Physiol Nutr Metab 2020; 45: 927-936
• 45 Drake JC, Wilson RJ, Yan Z. Molecular mechanisms for mitochondrial adaptation to exercise training in skeletal muscle. FASEB J 2016; 30: 13-22
• 46 Lin J, Wu H, Tarr PT. et al. Transcriptional co-activator PGC-1 alpha drives the formation of slow-twitch muscle fibres. Nature 2002; 418: 797-801
• 47 Geng T, Li P, Okutsu M. et al. PGC-1alpha plays a functional role in exercise-induced mitochondrial biogenesis and angiogenesis but not fiber-type transformation in mouse skeletal muscle. Am J Physiol Cell Physiol 2010; 298: C572-C579
• 48 Tanner CB, Madsen SR, Hallowell DM. et al. Mitochondrial and performance adaptations to exercise training in mice lacking skeletal muscle LKB1. Am J Physiol Endocrinol Metab 2013; 305: E1018-E1029
• 49 Trewin AJ, Berry BJ, Wojtovich AP. Exercise and mitochondrial dynamics: keeping in shape with ROS and AMPK. Antioxidants (Basel) 2018; 7: 7
• 50 Bengal E, Aviram S, Hayek T. p38 MAPK in glucose metabolism of skeletal muscle: Beneficial or harmful?. Int J Mol Sci 2020; 21: 6480
• 51 Hood DA, Memme JM, Oliveira AN. et al. Maintenance of skeletal muscle mitochondria in health, exercise, and aging. Annu Rev Physiol 2019; 81: 19-41
• 52 Spinelli JB, Haigis MC. The multifaceted contributions of mitochondria to cellular metabolism. Nat Cell Biol 2018; 20: 745-754
• 53 Gustafsson AB, Dorn GW. Evolving and expanding the roles of mitophagy as a homeostatic and pathogenic process. Physiol Rev 2019; 99: 853-892
• 54 Hall AR, Burke N, Dongworth RK. et al. Mitochondrial fusion and fission proteins: Novel therapeutic targets for combating cardiovascular disease. Br J Pharmacol 2014; 171: 1890-1906
• 55 Dorn GW. 2nd KR The mitochondrial dynamism-mitophagy-cell death interactome: Multiple roles performed by members of a mitochondrial molecular ensemble. Circ Res 2015; 116: 167-182
• 56 Romanello V, Sandri M. Mitochondrial quality control and muscle mass maintenance. Front Physiol 2015; 6: 422
• 57 Porter C, Reidy PT, Bhattarai N. et al. Resistance exercise training alters mitochondrial function in human skeletal muscle. Med Sci Sports Exerc 2015; 47: 1922-1931
• 58 Tang JE, Hartman JW, Phillips SM. Increased muscle oxidative potential following resistance training induced fibre hypertrophy in young men. Appl Physiol Nutr Metab 2006; 31: 495-501
• 59 Lim C, Kim HJ, Morton RW. et al. Resistance exercise-induced changes in muscle phenotype are load dependent. Med Sci Sports Exerc 2019; 51: 2578-2585
• 60 Salvadego D, Domenis R, Lazzer S. et al. Skeletal muscle oxidative function in vivo and ex vivo in athletes with marked hypertrophy from resistance training. J Appl Physiol (1985) 2013; 114: 1527-1535
• 61 Lee H, Kim K, Kim B. et al. A cellular mechanism of muscle memory facilitates mitochondrial remodelling following resistance training. J Physiol 2018; 596: 4413-4426
• 62 Kitaoka Y, Ogasawara R, Tamura Y. et al. Effect of electrical stimulation-induced resistance exercise on mitochondrial fission and fusion proteins in rat skeletal muscle. Appl Physiol Nutr Metab 2015; 40: 1137-1142
• 63 Uemichi K, Shirai T, Hanakita H. et al. Effect of mechanistic/mammalian target of rapamycin complex 1 on mitochondrial dynamics during skeletal muscle hypertrophy. Physiol Rep 2021; 9: e14789
• 64 Pesta D, Hoppel F, Macek C. et al. Similar qualitative and quantitative changes of mitochondrial respiration following strength and endurance training in normoxia and hypoxia in sedentary humans. Am J Physiol Regul Integr Comp Physiol 2011; 301: R1078-R1087
• 65 Groennebaek T, Jespersen NR, Jakobsgaard JE. et al. Skeletal muscle mitochondrial protein synthesis and respiration increase with low-load blood flow restricted as well as high-load resistance training. Front Physiol 2018; 9: 1796
• 66 Camera DM, Hawley JA, Coffey VG. Resistance exercise with low glycogen increases p53 phosphorylation and PGC-1alpha mRNA in skeletal muscle. Eur J Appl Physiol 2015; 115: 1185-1194
• 67 Hyatt HW, Powers SK. Mitochondrial dysfunction is a common denominator linking skeletal muscle wasting due to disease, aging, and prolonged inactivity. Antioxidants (Basel) 2021; 10: 588
• 68 Lee EJ, Neppl RL. Influence of age on skeletal muscle hypertrophy and atrophy signaling: established paradigms and unexpected links. Genes (Basel) 2021; 12: 688
• 69 Marcell TJ. Sarcopenia: causes, consequences, and preventions. J Gerontol A Biol Sci Med Sci 2003; 58: M911-M916
• 70 Holloway GP, Holwerda AM, Miotto PM. et al. Age-associated impairments in mitochondrial ADP sensitivity contribute to redox stress in senescent human skeletal muscle. Cell Rep 2018; 22: 2837-2848
• 71 Marcinek DJ, Schenkman KA, Ciesielski WA. et al. Reduced mitochondrial coupling in vivo alters cellular energetics in aged mouse skeletal muscle. J Physiol 2005; 569: 467-473
• 72 Zullo A, Fleckenstein J, Schleip R. et al. Structural and functional changes in the coupling of fascial tissue, skeletal muscle, and nerves during aging. Front Physiol 2020; 11: 592
• 73 Robinson MM, Dasari S, Konopka AR. et al. Enhanced protein translation underlies improved metabolic and physical adaptations to different exercise training modes in young and old humans. Cell Metab 2017; 25: 581-592
• 74 Flack KD, Davy BM, DeBerardinis M. et al. Resistance exercise training and in vitro skeletal muscle oxidative capacity in older adults. Physiol Rep 2016; 4: e12849
• 75 Parise G, Brose AN, Tarnopolsky MA. Resistance exercise training decreases oxidative damage to DNA and increases cytochrome oxidase activity in older adults. Exp Gerontol 2005; 40: 173-180
• 76 Mesquita PHC, Lamb DA, Parry HA. et al. Acute and chronic effects of resistance training on skeletal muscle markers of mitochondrial remodeling in older adults. Physiol Rep 2020; 8: e14526
• 77 Gharahdaghi N, Rudrappa S, Brook MS. et al. Testosterone therapy induces molecular programming augmenting physiological adaptations to resistance exercise in older men. J Cachexia Sarcopenia Muscle 2019; 10: 1276-1294
• 78 Miller MS, Callahan DM, Tourville TW. et al. Moderate-intensity resistance exercise alters skeletal muscle molecular and cellular structure and function in inactive older adults with knee osteoarthritis. J Appl Physiol (1985) 2017; 122: 775-787
• 79 Gilliam LA, St Clair DK. Chemotherapy-induced weakness and fatigue in skeletal muscle: The role of oxidative stress. Antioxid Redox Signal 2011; 15: 2543-2563
• 80 Mijwel S, Cardinale DA, Norrbom J. et al. Exercise training during chemotherapy preserves skeletal muscle fiber area, capillarization, and mitochondrial content in patients with breast cancer. FASEB J 2018; 32: 5495-5505
• 81 Groennebaek T, Sieljacks P, Nielsen R. et al. Effect of blood flow restricted resistance exercise and remote ischemic conditioning on functional capacity and myocellular adaptations in patients with heart failure. Circ Heart Fail 2019; 12: e006427
• 82 Bittel AJ, Bittel DC, Mittendorfer B. et al. A single bout of premeal resistance exercise improves postprandial glucose metabolism in obese men with prediabetes. Med Sci Sports Exerc 2021; 53: 694-703
• 83 Harriss DJ, Jones C, MacSween A. Ethical standards in sport and exercise science research: 2022 update. Int J Sports Med 2022; 43: 1065-1070