Skip to main content
Log in

Resistance exercise with low glycogen increases p53 phosphorylation and PGC-1α mRNA in skeletal muscle

  • Original Article
  • Published:
European Journal of Applied Physiology Aims and scope Submit manuscript

Abstract

Purpose

We determined the effect of reduced muscle glycogen availability on cellular pathways regulating mitochondrial biogenesis and substrate utilization after a bout of resistance exercise.

Methods

Eight young, recreationally trained men undertook a glycogen depletion protocol of one-leg cycling to fatigue (LOW), while the contralateral (control) leg rested (CONT). Following an overnight fast, subjects completed 8 sets of 5 unilateral leg press repetitions (REX) at 80 % 1 Repetition Maximum (1RM) on each leg. Subjects consumed 500 mL protein/CHO beverage (20 g whey + 40 g maltodextrin) upon completion of REX and 2 h later. Muscle biopsies were obtained at rest and 1 and 4 h after REX in both legs.

Results

Resting muscle glycogen was higher in the CONT than LOW leg (~384 ± 114 vs 184 ± 36 mmol kg−1 dry wt; P < 0.05), and 1 h and 4 h post-exercise (P < 0.05). Phosphorylation of p53Ser15 increased 1 h post-exercise in LOW (~115 %, P < 0.05) and was higher than CONT at this time point (~87 %, P < 0.05). p38MAPKThr180/Tyr182 phosphorylation increased 1 h post-exercise in both CONT and LOW (~800–900 %; P < 0.05) but remained above rest at 4 h only in CONT (~585 %, P < 0.05; different between legs P < 0.05). Peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) mRNA was elevated 4 h post-exercise in LOW (~200 %, P < 0.05; different between legs P < 0.05). There were no changes in Fibronectin type III domain-containing protein 5 (FNDC5) mRNA for CONT or LOW legs post-exercise.

Conclusion

Undertaking resistance exercise with low glycogen availability may enhance mitochondrial-related adaptations through p53 and PGC-1α-mediated signalling.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

Abbreviations

ACC:

Acetyl-CoA carboxylase

ANOVA:

Analysis of variance

CHO:

Carbohydrate

COXIV:

Cytochrome C oxidase IV

CONT:

Control

FNDC5:

Fibronectin type III domain-containing protein 5

GAPDH:

Glyceraldehyde-3-phosphate dehydrogenase

MAPK:

Mitogen-activated protein kinase

PDK4:

Pyruvate dehydrogenase kinase isozyme 4

PGC-1α:

Peroxisome proliferator-activated receptor gamma coactivator-1α

REX:

Resistance exercise

RM:

Repetition maximum

RT-qPCR:

Real-time quantitative polymerase chain reaction

Tfam:

Mitochondrial transcription factor A

VEGF:

Vascular endothelial growth factor

VO2peak :

Peak oxygen uptake

References

  • Apró W, Wang L, Pontén M, Blomstrand E, Sahlin K (2013) Resistance exercise induced mTORC1 signaling is not impaired by subsequent endurance exercise in human skeletal muscle. Am J Physiol Endocrinol Metab 305(1):E22–E32. doi:10.1152/ajpendo.00091.2013

    Article  PubMed  Google Scholar 

  • Balakrishnan VS, Rao M, Menon V, Gordon PL, Pilichowska M, Castaneda F, Castaneda-Sceppa C (2010) Resistance training increases muscle mitochondrial biogenesis in patients with chronic kidney disease. Clin J Am Soc Nephrol 5(6):996–1002. doi:10.2215/cjn.09141209

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Bartlett JD, Hwa Joo C, Jeong TS, Louhelainen J, Cochran AJ, Gibala MJ, Gregson W, Close GL, Drust B, Morton JP (2012) Matched work high-intensity interval and continuous running induce similar increases in PGC-1alpha mRNA, AMPK, p38, and p53 phosphorylation in human skeletal muscle. J Appl Physiol 112(7):1135–1143. doi:10.1152/japplphysiol.01040.2011

    Article  CAS  PubMed  Google Scholar 

  • Bartlett JD, Louhelainen J, Iqbal Z, Cochran AJ, Gibala MJ, Gregson W, Close GL, Drust B, Morton JP (2013) Reduced carbohydrate availability enhances exercise-induced p53 signaling in human skeletal muscle: implications for mitochondrial biogenesis. Am J Physiol Regul Integr Comp Physiol 304(6):R450–R458. doi:10.1152/ajpregu.00498.2012

    Article  CAS  PubMed  Google Scholar 

  • Bartlett JD, Close GL, Drust B, Morton JP (2014) The emerging role of p53 in exercise metabolism. Sports Med 44(3):303–309. doi:10.1007/s40279-013-0127-9

    Article  PubMed  Google Scholar 

  • Batterham A, Hopkins W (2006) Making meaningful inferences about magnitudes. Int J Sports Physiol Perform Mar 1(1):50–57

    Google Scholar 

  • Bostrom P, Wu J, Jedrychowski MP, Korde A, Ye L, Lo JC, Rasbach KA, Bostrom EA, Choi JH, Long JZ, Kajimura S, Zingaretti MC, Vind BF, Tu H, Cinti S, Hojlund K, Gygi SP, Spiegelman BM (2012) A PGC1-alpha-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature 481(7382):463–468. doi:10.1038/nature10777

    Article  PubMed Central  PubMed  Google Scholar 

  • Burd NA, Andrews RJ, West DWD, Little JP, Cochran AJR, Hector AJ, Cashaback JGA, Gibala MJ, Potvin JR, Baker SK, Phillips SM (2012) Muscle time under tension during resistance exercise stimulates differential muscle protein sub-fractional synthetic responses in men. J Physiol 590(2):351–362. doi:10.1113/jphysiol.2011.221200

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Camera DM, West DW, Burd NA, Phillips SM, Garnham AP, Hawley JA, Coffey VG (2012) Low muscle glycogen concentration does not suppress the anabolic response to resistance exercise. J Appl Physiol 113(2):206–214. doi:10.1152/japplphysiol.00395.2012

    Article  CAS  PubMed  Google Scholar 

  • Camera DM, West DW, Phillips SM, Rerecich T, Stellingwerff T, Hawley JA, Coffey VG (2015) Protein ingestion increases myofibrillar protein synthesis after concurrent exercise. Med Sci Sports Exerc 47(1):82–91

    Article  CAS  PubMed  Google Scholar 

  • Churchley EG, Coffey VG, Pedersen DJ, Shield A, Carey KA, Cameron-Smith D, Hawley JA (2007) Influence of preexercise muscle glycogen content on transcriptional activity of metabolic and myogenic genes in well-trained humans. J Appl Physiol 102(4):1604–1611. doi:10.1152/japplphysiol.01260.2006

    Article  CAS  PubMed  Google Scholar 

  • Cluberton LJ, McGee SL, Murphy RM, Hargreaves M (2005) Effect of carbohydrate ingestion on exercise-induced alterations in metabolic gene expression. J Appl Physiol 99(4):1359–1363. doi:10.1152/japplphysiol.00197.2005

    Article  CAS  PubMed  Google Scholar 

  • Coffey VG, Zhong Z, Shield A, Canny BJ, Chibalin AV, Zierath JR, Hawley JA (2005) Early signaling responses to divergent exercise stimuli in skeletal muscle from well-trained humans. FASEB J. doi:10.1096/fj.05-4809fje

    PubMed  Google Scholar 

  • Coffey VG, Jemiolo B, Edge J, Garnham AP, Trappe SW, Hawley JA (2009) Effect of consecutive repeated sprint and resistance exercise bouts on acute adaptive responses in human skeletal muscle. Am J Physiol Regul Integr Comp Physiol 297(5):R1441–R1451. doi:10.1152/ajpregu.00351.2009

    Article  CAS  PubMed  Google Scholar 

  • Gordon PM, Liu D, Sartor MA, IglayReger HB, Pistilli EE, Gutmann L, Nader GA, Hoffman EP (2012) Resistance exercise training influences skeletal muscle immune activation: a microarray analysis. J Appl Physiol 112(3):443–453. doi:10.1152/japplphysiol.00860.2011

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Hakkinen K, Newton RU, Gordon SE, McCormick M, Volek JS, Nindl BC, Gotshalk LA, Campbell WW, Evans WJ, Hakkinen A, Humphries BJ, Kraemer WJ (1998) Changes in muscle morphology, electromyographic activity, and force production characteristics during progressive strength training in young and older men. J Gerontol Ser A Biol Sci Med Sci 53(6):B415–B423

    Article  CAS  Google Scholar 

  • Hawley JA, Morton JP (2014) Ramping up the signal: promoting endurance training adaptation in skeletal muscle by nutritional manipulation. Clin Exp Pharmacol Physiol 41(8):608–613. doi:10.1111/1440-1681.12246

    Article  CAS  PubMed  Google Scholar 

  • Hawley J, Noakes T (1992) Peak power output predicts maximal oxygen uptake and performance time in trained cyclists. Eur J Appl Physiol 65(1):79–83

    Article  CAS  Google Scholar 

  • Hickson R (1980) Interference of strength development by simultaneously training for strength and endurance. Eur J Appl Physiol Occup Physiol 45(2–3):255–263

    Article  CAS  PubMed  Google Scholar 

  • Hopkins W, Marshall S, Batterham A, Hanin J (2009) Progressive statistics for studies in sports medicine and exercise science. Med Sci Sport Exer 41(1):3–13

    Article  Google Scholar 

  • Jemiolo B, Trappe S (2004) Single muscle fiber gene expression in human skeletal muscle: validation of internal control with exercise. Biochem Biophys Res Commun 320(3):1043–1050. doi:10.1016/j.bbrc.2004.05.223

    Article  CAS  PubMed  Google Scholar 

  • Jones RG, Plas DR, Kubek S, Buzzai M, Mu J, Xu Y, Birnbaum MJ, Thompson CB (2005) AMP-activated protein kinase induces a p53-dependent metabolic checkpoint. Mol Cell 18(3):283–293. doi:10.1016/j.molcel.2005.03.027

    Article  CAS  PubMed  Google Scholar 

  • Koopman R, Zorenc AHG, Gransier RJJ, Cameron-Smith D, van Loon LJC (2006) Increase in S6K1 phosphorylation in human skeletal muscle following resistance exercise occurs mainly in type II muscle fibers. Am J Physiol Endocrinol Metab 290(6):E1245–E1252. doi:10.1152/ajpendo.00530.2005

    Article  CAS  PubMed  Google Scholar 

  • Kuhl JE, Ruderman NB, Musi N, Goodyear LJ, Patti ME, Crunkhorn S, Dronamraju D, Thorell A, Nygren J, Ljungkvist O, Degerblad M, Stahle A, Brismar TB, Andersen KL, Saha AK, Efendic S, Bavenholm PN (2006) Exercise training decreases the concentration of malonyl-CoA and increases the expression and activity of malonyl-CoA decarboxylase in human muscle. Am J Physiol Endocrinol Metab 290(6):E1296–E1303. doi:10.1152/ajpendo.00341.2005

    Article  CAS  PubMed  Google Scholar 

  • Little JP, Safdar A, Bishop D, Tarnopolsky MA, Gibala MJ (2011) An acute bout of high-intensity interval training increases the nuclear abundance of PGC-1α and activates mitochondrial biogenesis in human skeletal muscle. Am J Physiol Regul Integr Comp Physiol 300(6):R1303–R1310. doi:10.1152/ajpregu.00538.2010

    Article  CAS  PubMed  Google Scholar 

  • Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2−ΔΔCT Method. Methods 25(4):402–408. doi:10.1006/meth.2001.1262

    Article  CAS  PubMed  Google Scholar 

  • Maughan RJ, Poole DC (1981) The effects of a glycogen-loading regimen on the capacity to perform anaerobic exercise. Eur J Appl Physiol Occup Physiol 46(3):211–219

    Article  CAS  PubMed  Google Scholar 

  • Park JY, Wang PY, Matsumoto T, Sung HJ, Ma W, Choi JW, Anderson SA, Leary SC, Balaban RS, Kang JG, Hwang PM (2009) p53 improves aerobic exercise capacity and augments skeletal muscle mitochondrial DNA content. Circ Res 105(7):705–712. doi:10.1161/circresaha.109.205310

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Pekkala S, Wiklund PK, Hulmi JJ, Ahtiainen JP, Horttanainen M, Pollanen E, Makela KA, Kainulainen H, Hakkinen K, Nyman K, Alen M, Herzig KH, Cheng S (2013) Are skeletal muscle FNDC5 gene expression and irisin release regulated by exercise and related to health? J Physiol 591(Pt 21):5393–5400. doi:10.1113/jphysiol.2013.263707

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Perry CGR, Lally J, Holloway GP, Heigenhauser GJF, Bonen A, Spriet LL (2010) Repeated transient mRNA bursts precede increases in transcriptional and mitochondrial proteins during training in human skeletal muscle. J Physiol 588(23):4795–4810. doi:10.1113/jphysiol.2010.199448

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Psilander N, Frank P, Flockhart M, Sahlin K (2013) Exercise with low glycogen increases PGC-1alpha gene expression in human skeletal muscle. Eur J Appl Physiol 113(4):951–963. doi:10.1007/s00421-012-2504-8

    Article  CAS  PubMed  Google Scholar 

  • Saleem A, Hood DA (2013) Acute exercise induces tumour suppressor protein p53 translocation to the mitochondria and promotes a p53–Tfam–mitochondrial DNA complex in skeletal muscle. J Physiol 591(Pt 14):3625–3636. doi:10.1113/jphysiol.2013.252791

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Saleem A, Adhihetty PJ, Hood DA (2009) Role of p53 in mitochondrial biogenesis and apoptosis in skeletal muscle. Physiol Gen 37(1):58–66. doi:10.1152/physiolgenomics.90346.2008

    Article  CAS  Google Scholar 

  • Saleem A, Carter HN, Hood DA (2014) p53 is necessary for the adaptive changes in cellular milieu subsequent to an acute bout of endurance exercise. Am J Physiol Cell Physiol 306(3):C241–C249. doi:10.1152/ajpcell.00270.2013

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Salvadego D, Domenis R, Lazzer S, Porcelli S, Rittweger J, Rizzo G, Mavelli I, Simunic B, Pisot R, Grassi B (2013) Skeletal muscle oxidative function in vivo and ex vivo in athletes with marked hypertrophy from resistance training. J Appl Physiol 114(11):1527–1535. doi:10.1152/japplphysiol.00883.2012

    Article  CAS  PubMed  Google Scholar 

  • She QB, Bode AM, Ma WY, Chen NY, Dong Z (2001) Resveratrol-induced activation of p53 and apoptosis is mediated by extracellular-signal-regulated protein kinases and p38 kinase. Cancer Res 61(4):1604–1610

    CAS  PubMed  Google Scholar 

  • Tam BT, Siu PM (2014) Autophagic cellular responses to physical exercise in skeletal muscle. Sports Med 44(5):625–640. doi:10.1007/s40279-013-0140-z

    Article  PubMed  Google Scholar 

  • Tang JE, Hartman JW, Phillips SM (2006) Increased muscle oxidative potential following resistance training induced fibre hypertrophy in young men. Appl Physiol Nutr Metab 31(5):495–501. doi:10.1139/h06-026

    Article  CAS  PubMed  Google Scholar 

  • Wang L, Sahlin K (2012) The effect of continuous and interval exercise on PGC-1alpha and PDK4 mRNA in type I and type II fibres of human skeletal muscle. Acta Physiol 204(4):525–532. doi:10.1111/j.1748-1716.2011.02354.x

    Article  CAS  Google Scholar 

  • Wang L, Mascher H, Psilander N, Blomstrand E, Sahlin K (2011) Resistance exercise enhances the molecular signaling of mitochondrial biogenesis induced by endurance exercise in human skeletal muscle. J Appl Physiol 111(5):1335–1344. doi:10.1152/japplphysiol.00086.2011

    Article  CAS  PubMed  Google Scholar 

  • Yang Y, Creer A, Jemiolo B, Trappe S (2005) Time course of myogenic and metabolic gene expression in response to acute exercise in human skeletal muscle. J Appl Physiol 98(5):1745–1752. doi:10.1152/japplphysiol.01185.2004

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We thank Fonterra Co-Operative Group Limited, Australia for the gift of whey protein for this study. The authors declare no conflicts of interest.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Donny M. Camera.

Additional information

Communicated by Michael Lindinger.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Camera, D.M., Hawley, J.A. & Coffey, V.G. Resistance exercise with low glycogen increases p53 phosphorylation and PGC-1α mRNA in skeletal muscle. Eur J Appl Physiol 115, 1185–1194 (2015). https://doi.org/10.1007/s00421-015-3116-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00421-015-3116-x

Keywords

Navigation