Benefits of higher resistance-training volume are related to ribosome biogenesis

Daniel Hammarström, Sjur Øfsteng, Lise Koll, Marita Hanestadhaugen, Ivana Hollan, William Apró, Jon Elling Whist, Eva Blomstrand, Bent R Rønnestad, Stian Ellefsen, Daniel Hammarström, Sjur Øfsteng, Lise Koll, Marita Hanestadhaugen, Ivana Hollan, William Apró, Jon Elling Whist, Eva Blomstrand, Bent R Rønnestad, Stian Ellefsen

Abstract

Key points: For individuals showing suboptimal adaptations to resistance training, manipulation of training volume is a potential measure to facilitate responses. This remains unexplored. Here, 34 untrained individuals performed contralateral resistance training with moderate and low volume for 12 weeks. Moderate volume led to larger increases in muscle cross-sectional area, strength and type II fibre-type transitions. These changes coincided with greater activation of signalling pathways controlling muscle growth and greater induction of ribosome synthesis. Out of 34 participants, thirteen displayed clear benefit of MOD on muscle hypertrophy and sixteen showed clear benefit of MOD on muscle strength gains. This coincided with greater total RNA accumulation in the early phase of the training period, suggesting that ribosomal biogenesis regulates the dose-response relationship between training volume and muscle hypertrophy. These results demonstrate that there is a dose-dependent relationship between training volume and outcomes. On the individual level, benefits of higher training volume were associated with increased ribosomal biogenesis.

Abstract: Resistance-exercise volume is a determinant of training outcomes. However not all individuals respond in a dose-dependent fashion. In this study, 34 healthy individuals (males n = 16, 23.6 (4.1) years; females n = 18, 22.0 (1.3) years) performed moderate- (3 sets per exercise, MOD) and low-volume (1 set, LOW) resistance training in a contralateral fashion for 12 weeks (2-3 sessions per week). Muscle cross-sectional area (CSA) and strength were assessed at Weeks 0 and 12, along with biopsy sampling (m. vastus lateralis). Muscle biopsies were also sampled before and 1 h after the fifth session (Week 2). MOD resulted in larger increases in muscle CSA (5.2 (3.8)% versus 3.7 (3.7)%, P < 0.001) and strength (3.4-7.7% difference, all P < 0.05. This coincided with greater reductions in type IIX fibres from Week 0 to Week 12 (MOD, -4.6 percentage points; LOW -3.2 percentage points), greater phosphorylation of S6-kinase 1 (p85 S6K1Thr412 , 19%; p70 S6K1Thr389 , 58%) and ribosomal protein S6Ser235/236 (37%), greater rested-state total RNA (8.8%) and greater exercise-induced c-Myc mRNA expression (25%; Week 2, all P < 0.05). Thirteen and sixteen participants, respectively, displayed clear benefits in response to MOD on muscle hypertrophy and strength. Benefits were associated with greater accumulation of total RNA at Week 2 in the MOD leg, with every 1% difference increasing the odds of MOD benefit by 7.0% (P = 0.005) and 9.8% (P = 0.002). In conclusion, MOD led to greater functional and biological adaptations than LOW. Associations between dose-dependent total RNA accumulation and increases in muscle mass and strength point to ribosome biogenesis as a determinant of dose-dependent training responses.

Keywords: resistance-training; ribosome biogenesis; training-volume.

© 2019 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.

References

    1. Ahtiainen JP, Walker S, Peltonen H, Holviala J, Sillanpaa E, Karavirta L, Sallinen J, Mikkola J, Valkeinen H, Mero A, Hulmi JJ & Hakkinen K (2016). Heterogeneity in resistance training-induced muscle strength and mass responses in men and women of different ages. Age (Dordr) 38, 10.
    1. Ahtiainen JP, Walker S, Silvennoinen M, Kyrolainen H, Nindl BC, Hakkinen K, Nyman K, Selanne H & Hulmi JJ (2015). Exercise type and volume alter signaling pathways regulating skeletal muscle glucose uptake and protein synthesis. Eur J Appl Physiol 115, 1835-1845.
    1. Andersen JL & Aagaard P (2000). Myosin heavy chain IIX overshoot in human skeletal muscle. Muscle Nerve 23, 1095-1104.
    1. Andersen JL & Gruschy-Knudsen T (2018). Rapid switch-off of the human myosin heavy chain IIX gene after heavy load muscle contractions is sustained for at least four days. Scand J Med Sci Sports 28, 371-380.
    1. Bates D, Mächler M, Bolker B & Walker S (2015). Fitting linear mixed-effects models using lme4. J Stat Softw 67, 48.
    1. Brook MS, Wilkinson DJ, Mitchell WK, Lund JN, Phillips BE, Szewczyk NJ, Greenhaff PL, Smith K & Atherton PJ (2016). Synchronous deficits in cumulative muscle protein synthesis and ribosomal biogenesis underlie age-related anabolic resistance to exercise in humans. J Physiol 594, 7399-7417.
    1. Burd NA, Holwerda AM, Selby KC, West DW, Staples AW, Cain NE, Cashaback JG, Potvin JR, Baker SK & Phillips SM (2010). Resistance exercise volume affects myofibrillar protein synthesis and anabolic signalling molecule phosphorylation in young men. J Physiol 588, 3119-3130.
    1. Cannon J & Marino FE (2010). Early-phase neuromuscular adaptations to high- and low-volume resistance training in untrained young and older women. J Sports Sci 28, 1505-1514.
    1. Carpinelli RN & Otto RM (1998). Strength training. Single versus multiple sets. Sports Med 26, 73-84.
    1. Chaillou T, Kirby TJ & McCarthy JJ (2014). Ribosome biogenesis: Emerging evidence for a central role in the regulation of skeletal muscle mass. J Cell Physiol 229, 1584-1594.
    1. Chauvin C, Koka V, Nouschi A, Mieulet V, Hoareau-Aveilla C, Dreazen A, Cagnard N, Carpentier W, Kiss T, Meyuhas O & Pende M (2014). Ribosomal protein s6 kinase activity controls the ribosome biogenesis transcriptional program. Oncogene 33, 474-483.
    1. Chiang GG & Abraham RT (2005). Phosphorylation of mammalian target of rapamycin (mTOR) at Ser-2448 is mediated by p70S6 kinase. J Biol Chem 280, 25485-25490.
    1. Choi J, Lee M, Lee JK, Kang D & Choi JY (2017). Correlates associated with participation in physical activity among adults: A systematic review of reviews and update. BMC Public Health 17, 356.
    1. Damas F, Phillips SM, Libardi CA, Vechin FC, Lixandrão ME, Jannig PR, Costa LAR, Bacurau AV, Snijders T, Parise G, Tricoli V, Roschel H & Ugrinowitsch C (2016). Resistance training-induced changes in integrated myofibrillar protein synthesis are related to hypertrophy only after attenuation of muscle damage. J Physiol 594, 5209-5222.
    1. Drummond MJ, Fry CS, Glynn EL, Dreyer HC, Dhanani S, Timmerman KL, Volpi E & Rasmussen BB (2009). Rapamycin administration in humans blocks the contraction-induced increase in skeletal muscle protein synthesis. J Physiol 587, 1535-1546.
    1. Eftestol E, Egner IM, Lunde IG, Ellefsen S, Andersen T, Sjaland C, Gundersen K & Bruusgaard JC (2016). Increased hypertrophic response with increased mechanical load in skeletal muscles receiving identical activity patterns. Am J Physiol Cell Physiol 311, C616-C629.
    1. Ellefsen S, Stenslokken KO, Sandvik GK, Kristensen TA & Nilsson GE (2008). Improved normalization of real-time reverse transcriptase polymerase chain reaction data using an external RNA control. Anal Biochem 376, 83-93.
    1. Ellefsen S, Vikmoen O, Slettalokken G, Whist JE, Nygaard H, Hollan I, Rauk I, Vegge G, Strand TA, Raastad T & Ronnestad BR (2014a). Irisin and FNDC5: Effects of 12-week strength training, and relations to muscle phenotype and body mass composition in untrained women. Eur J Appl Physiol 114, 1875-1888.
    1. Ellefsen S, Vikmoen O, Zacharoff E, Rauk I, Slettalokken G, Hammarstrom D, Strand TA, Whist JE, Hanestadhaugen M, Vegge G, Fagernes CE, Nygaard H, Hollan I & Ronnestad BR (2014b). Reliable determination of training-induced alterations in muscle fiber composition in human skeletal muscle using quantitative polymerase chain reaction. Scand J Med Sci Sports 24, e332-e342.
    1. Figueiredo VC, Caldow MK, Massie V, Markworth JF, Cameron-Smith D & Blazevich AJ (2015). Ribosome biogenesis adaptation in resistance training-induced human skeletal muscle hypertrophy. Am J Physiol Endocrinol Metab 309, E72-E83.
    1. Figueiredo VC, Markworth JF & Cameron-Smith D (2017). Considerations on mTOR regulation at serine 2448: Implications for muscle metabolism studies. Cell Mol Life Sci 74, 2537-2545.
    1. Figueiredo VC & McCarthy JJ (2019). Regulation of ribosome biogenesis in skeletal muscle hypertrophy. Physiology (Bethesda) 34, 30-42.
    1. Figueiredo VC, Roberts LA, Markworth JF, Barnett MP, Coombes JS, Raastad T, Peake JM & Cameron-Smith D (2016). Impact of resistance exercise on ribosome biogenesis is acutely regulated by post-exercise recovery strategies. Physiol Rep 4, e12670.
    1. Figueiredo VC, Zeng N, D'Souza RF, Markworth JF, Della Gatta PA, Petersen A, Barnett MPG & Cameron-Smith D (2018). High dose of whey protein after resistance exercise promotes 45 S preribosomal RNA synthesis in older men. Nutrition 50, 105-107.
    1. Fleige S & Pfaffl MW (2006). RNA integrity and the effect on the real-time qRT-PCR performance. Mol Aspects Med 27, 126-139.
    1. Fyfe JJ, Bishop DJ, Bartlett JD, Hanson ED, Anderson MJ, Garnham AP & Stepto NK (2018). Enhanced skeletal muscle ribosome biogenesis, yet attenuated mTORC1 and ribosome biogenesis-related signalling, following short-term concurrent versus single-mode resistance training. Sci Rep 8, 560.
    1. Goodman CA, Frey JW, Mabrey DM, Jacobs BL, Lincoln HC, You JS & Hornberger TA (2011). The role of skeletal muscle mTOR in the regulation of mechanical load-induced growth. J Physiol 589, 5485-5501.
    1. Henras AK, Plisson-Chastang C, O'Donohue M-F, Chakraborty A & Gleizes P-E (2015). An overview of pre-ribosomal RNA processing in eukaryotes. Wiley Interdiscip Rev RNA 6, 225-242.
    1. Hosmer DW, Lemeshow S & Sturdivant RX (2013). Applied Logistic Regression, 3rd edn. Wiley, Hoboken, New Jersey.
    1. Jespersen JG, Nedergaard A, Andersen LL, Schjerling P & Andersen JL (2011). Myostatin expression during human muscle hypertrophy and subsequent atrophy: Increased myostatin with detraining. Scand J Med Sci Sports 21, 215-223.
    1. Kim PL, Staron RS & Phillips SM (2005). Fasted-state skeletal muscle protein synthesis after resistance exercise is altered with training. J Physiol 568, 283-290.
    1. Kosmidis I (2019). Brglm2: Bias Reduction in Generalized Linear Models. Available at: .
    1. Krieger JW (2009). Single versus multiple sets of resistance exercise: A meta-regression. J Strength Cond Res 23, 1890-1901.
    1. Krieger JW (2010). Single vs. multiple sets of resistance exercise for muscle hypertrophy: A meta-analysis. J Strength Cond Res 24, 1150-1159.
    1. Luo W, Chen J, Li L, Ren X, Cheng T, Lu S, Lawal RA, Nie Q, Zhang X & Hanotte O (2019). C-myc inhibits myoblast differentiation and promotes myoblast proliferation and muscle fibre hypertrophy by regulating the expression of its target genes, miRNAs and lincRNAs. Cell Death Differ 26, 426-442.
    1. Magnusson A, Skaug H, Nielsen A, Berg C, Kristensen K, Maechler M, van Bentham K, Bolker B & Brooks M (2019). GlmmTMB: Generalized Linear Mixed Models using Template Model Builder. Available at: .
    1. Matz MV, Wright RM & Scott JG (2013). No control genes required: Bayesian analysis of qRT-PCR data. PLoS One 8, e71448.
    1. Millward DJ, Garlick PJ, James WPT, Nnanyelugo DO & Ryatt JS (1973). Relationship between protein synthesis and RNA content in skeletal muscle. Nature 241, 204-205.
    1. Mitchell CJ, Churchward-Venne TA, Bellamy L, Parise G, Baker SK & Phillips SM (2013). Muscular and systemic correlates of resistance training-induced muscle hypertrophy. PLoS One 8, e78636.
    1. Mitchell CJ, Churchward-Venne TA, West DW, Burd NA, Breen L, Baker SK & Phillips SM (2012). Resistance exercise load does not determine training-mediated hypertrophic gains in young men. J Appl Physiol (1985) 113, 71-77.
    1. Mobley CB, Haun CT, Roberson PA, Mumford PW, Kephart WC, Romero MA, Osburn SC, Vann CG, Young KC, Beck DT, Martin JS, Lockwood CM & Roberts MD (2018). Biomarkers associated with low, moderate, and high vastus lateralis muscle hypertrophy following 12 weeks of resistance training. PLoS One 13, e0195203.
    1. Morton RW, Murphy KT, McKellar SR, Schoenfeld BJ, Henselmans M, Helms E, Aragon AA, Devries MC, Banfield L, Krieger JW & Phillips SM (2018). A systematic review, meta-analysis and meta-regression of the effect of protein supplementation on resistance training-induced gains in muscle mass and strength in healthy adults. Br J Sports Med 52, 376-384.
    1. Nader GA, McLoughlin TJ & Esser KA (2005). MTOR function in skeletal muscle hypertrophy: Increased ribosomal RNA via cell cycle regulators. Am J Physiol Cell Physiol 289, C1457-C1465.
    1. Nader GA, von Walden F, Liu C, Lindvall J, Gutmann L, Pistilli EE & Gordon PM (2014). Resistance exercise training modulates acute gene expression during human skeletal muscle hypertrophy. J Appl Physiol (1985) 116, 693-702.
    1. Nemes S, Jonasson JM, Genell A & Steineck G (2009). Bias in odds ratios by logistic regression modelling and sample size. BMC Med Res Methodol 9, 56.
    1. Nüesch E, Trelle S, Reichenbach S, Rutjes AWS, Tschannen B, Altman DG, Egger M & Jüni P (2010). Small study effects in meta-analyses of osteoarthritis trials: Meta-epidemiological study. BMJ 341, c3515.
    1. Ostrowski KJ, Wilson GJ, Weatherby R, Murphy PW & Lyttle AD (1997). The effect of weight training volume on hormonal output and muscular size and function. J Strength Cond Res 11, 148-154.
    1. Pareja-Blanco F, Rodriguez-Rosell D, Sanchez-Medina L, Sanchis-Moysi J, Dorado C, Mora-Custodio R, Yanez-Garcia JM, Morales-Alamo D, Perez-Suarez I, Calbet JAL & Gonzalez-Badillo JJ (2017). Effects of velocity loss during resistance training on athletic performance, strength gains and muscle adaptations. Scand J Med Sci Sports 27, 724-735.
    1. Phillips BE, Williams JP, Greenhaff PL, Smith K & Atherton PJ (2017). Physiological adaptations to resistance exercise as a function of age. JCI Insight 2, e95581.
    1. Pinheiro JC & Bates DM (2000). Mixed-Effects Models in S and S-PLUS. Springer, New York.
    1. Ratamess N, Alvar BA, Evetoch TK, Housh TJ, Kibler B, Kraemer WJ & Triplett NT (2009). American College of Sports Medicine position stand. Progression models in resistance training for healthy adults. Med Sci Sports Exerc 41, 687-708.
    1. Raue U, Trappe TA, Estrem ST, Qian HR, Helvering LM, Smith RC & Trappe S (2012). Transcriptome signature of resistance exercise adaptations: Mixed muscle and fiber type specific profiles in young and old adults. J Appl Physiol (1985) 112, 1625-1636.
    1. R Core Team (2018). R: A Language and Environment for Statistical Computing. R Foundation for Statistical Computing, Vienna, Austria. Available at: .
    1. Reidy PT, Borack MS, Markofski MM, Dickinson JM, Fry CS, Deer RR, Volpi E & Rasmussen BB (2017). Post-absorptive muscle protein turnover affects resistance training hypertrophy. Eur J Appl Physiol 117, 853-866.
    1. Rhea MR, Alvar BA, Ball SD & Burkett LN (2002). Three sets of weight training superior to 1 set with equal intensity for eliciting strength. J Strength Cond Res 16, 525-529.
    1. Rhea MR, Alvar BA, Burkett LN & Ball SD (2003). A meta-analysis to determine the dose response for strength development. Med Sci Sports Exerc 35, 456-464.
    1. Ritz C & Spiess AN (2008). qpcR: An R package for sigmoidal model selection in quantitative real-time polymerase chain reaction analysis. Bioinformatics 24, 1549-1551.
    1. Ronnestad BR, Egeland W, Kvamme NH, Refsnes PE, Kadi F & Raastad T (2007). Dissimilar effects of one- and three-set strength training on strength and muscle mass gains in upper and lower body in untrained subjects. J Strength Cond Res 21, 157-163.
    1. Roux PP, Shahbazian D, Vu H, Holz MK, Cohen MS, Taunton J, Sonenberg N & Blenis J (2007). RAS/ERK signaling promotes site-specific ribosomal protein S6 phosphorylation via RSK and stimulates Cap-dependent translation. J Biol Chem 282, 14056-14064.
    1. Rueden CT, Schindelin J, Hiner MC, DeZonia BE, Walter AE, Arena ET & Eliceiri KW (2017). ImageJ2: ImageJ for the next generation of scientific image data. BMC Bioinformatics 18, 529.
    1. Schoenfeld BJ, Ogborn D & Krieger JW (2016). Dose-response relationship between weekly resistance training volume and increases in muscle mass: A systematic review and meta-analysis. J Sports Sci 35, 1-10.
    1. Seaborne RA, Strauss J, Cocks M, Shepherd S, O'Brien TD, van Someren KA, Bell PG, Murgatroyd C, Morton JP, Stewart CE & Sharples AP (2018). Human skeletal muscle possesses an epigenetic memory of hypertrophy. Sci Rep 8, 1898.
    1. Sennepin AD, Charpentier S, Normand T, Sarre C, Legrand A & Mollet LM (2009). Multiple reprobing of western blots after inactivation of peroxidase activity by its substrate, hydrogen peroxide. Anal Biochem 393, 129-131.
    1. Starkey DB, Pollock ML, Ishida Y, Welsch MA, Brechue WF, Graves JE & Feigenbaum MS (1996). Effect of resistance training volume on strength and muscle thickness. Med Sci Sports Exerc 28, 1311-1320.
    1. Stec MJ, Kelly NA, Many GM, Windham ST, Tuggle SC & Bamman MM (2016). Ribosome biogenesis may augment resistance training-induced myofiber hypertrophy and is required for myotube growth in vitro. Am J Physiol Endocrinol Metab 310, E652-E661.
    1. Stec MJ, Mayhew DL & Bamman MM (2015). The effects of age and resistance loading on skeletal muscle ribosome biogenesis. J Appl Physiol (1985) 119, 851-857.
    1. Terzis G, Georgiadis G, Stratakos G, Vogiatzis I, Kavouras S, Manta P, Mascher H & Blomstrand E (2008). Resistance exercise-induced increase in muscle mass correlates with p70S6 kinase phosphorylation in human subjects. Eur J Appl Physiol 102, 145-152.
    1. Terzis G, Spengos K, Mascher H, Georgiadis G, Manta P & Blomstrand E (2010). The degree of p70 S6k and S6 phosphorylation in human skeletal muscle in response to resistance exercise depends on the training volume. Eur J Appl Physiol 110, 835-843.
    1. Thalacker-Mercer A, Stec M, Cui X, Cross J, Windham S & Bamman M (2013). Cluster analysis reveals differential transcript profiles associated with resistance training-induced human skeletal muscle hypertrophy. Physiol Genomics 45, 499-507.
    1. Tichopad A, Dilger M, Schwarz G & Pfaffl MW (2003). Standardized determination of real-time PCR efficiency from a single reaction set-up. Nucleic Acids Res 31, e122.
    1. Timmons JA (2011). Variability in training-induced skeletal muscle adaptation. J Appl Physiol (1985) 110, 846-853.
    1. Untergasser A, Cutcutache I, Koressaar T, Ye J, Faircloth BC, Remm M & Rozen SG (2012). Primer3 - new capabilities and interfaces. Nucleic Acids Res 40, e115.
    1. van Riggelen J, Yetil A & Felsher DW (2010). MYC as a regulator of ribosome biogenesis and protein synthesis. Nat Rev Cancer 10, 301-309.
    1. von Walden F, Casagrande V, Ostlund Farrants AK & Nader GA (2012). Mechanical loading induces the expression of a Pol I regulon at the onset of skeletal muscle hypertrophy. Am J Physiol Cell Physiol 302, C1523-C1530.
    1. von Walden F, Liu C, Aurigemma N & Nader GA (2016). MTOR signaling regulates myotube hypertrophy by modulating protein synthesis, rDNA transcription and chromatin remodeling. Am J Physiol Cell Physiol 311, C663-C672.
    1. West DW, Baehr LM, Marcotte GR, Chason CM, Tolento L, Gomes AV, Bodine SC & Baar K (2016). Acute resistance exercise activates rapamycin-sensitive and -insensitive mechanisms that control translational activity and capacity in skeletal muscle. J Physiol 594, 453-468.
    1. Widrick JJ, Stelzer JE, Shoepe TC & Garner DP (2002). Functional properties of human muscle fibers after short-term resistance exercise training. Am J Physiol Regul Integr Comp Physiol 283, R408-R416.
    1. Wilkinson SB, Tarnopolsky MA, Grant EJ, Correia CE & Phillips SM (2006). Hypertrophy with unilateral resistance exercise occurs without increases in endogenous anabolic hormone concentration. Eur J Appl Physiol 98, 546-555.
    1. Ye J, Coulouris G, Zaretskaya I, Cutcutache I, Rozen S & Madden TL (2012). Primer-blast: A tool to design target-specific primers for polymerase chain reaction. BMC Bioinformatics 13, 134.
    1. Zak R, Rabinowitz M & Platt C (1967). Ribonucleic acids associated with myofibrils. Biochemistry 6, 2493-2499.

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