Skip to main content

Exercise with low glycogen increases PGC-1α gene expression in human skeletal muscle

European Journal of Applied Physiology volume 113, pages 951–963 (2013)Cite this article

Abstract

Recent studies suggest that carbohydrate restriction can improve the training-induced adaptation of muscle oxidative capacity. However, the importance of low muscle glycogen on the molecular signaling of mitochondrial biogenesis remains unclear. Here, we compare the effects of exercise with low (LG) and normal (NG) glycogen on different molecular factors involved in the regulation of mitochondrial biogenesis. Ten highly trained cyclists (VO2max 65 ± 1 ml/kg/min, W max 387 ± 8 W) exercised for 60 min at approximately 64 % VO2max with either low [166 ± 21 mmol/kg dry weight (dw)] or normal (478 ± 33 mmol/kg dw) muscle glycogen levels achieved by prior exercise/diet intervention. Muscle biopsies were taken before, and 3 h after, exercise. The mRNA of peroxisome proliferator-activated receptor-γ coactivator-1 was enhanced to a greater extent when exercise was performed with low compared with normal glycogen levels (8.1-fold vs. 2.5-fold increase). Cytochrome c oxidase subunit I and pyruvate dehydrogenase kinase isozyme 4 mRNA were increased after LG (1.3- and 114-fold increase, respectively), but not after NG. Phosphorylation of AMP-activated protein kinase, p38 mitogen-activated protein kinases and acetyl-CoA carboxylase was not changed 3 h post-exercise. Mitochondrial reactive oxygen species production and glutathione oxidative status tended to be reduced 3 h post-exercise. We conclude that exercise with low glycogen levels amplifies the expression of the major genetic marker for mitochondrial biogenesis in highly trained cyclists. The results suggest that low glycogen exercise may be beneficial for improving muscle oxidative capacity.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

USD 39.95

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

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

References

  • Baar K, McGee S (2008) Optimizing training adaptations by manipulating glycogen. Eur J Sport Sci 8:97–106

    Article  Google Scholar 

  • Bergstrom J (1975) Percutaneous needle biopsy of skeletal muscle in physiological and clinical research. Scand J Clin Lab Invest 35:609–616

    PubMed  Article  CAS  Google Scholar 

  • Bergstrom J, Hermansen L, Hultman E, Saltin B (1967) Diet, muscle glycogen and physical performance. Acta Physiol Scand 71:140–150

    PubMed  Article  CAS  Google Scholar 

  • Broberg S, Sahlin K (1989) Adenine nucleotide degradation in human skeletal muscle during prolonged exercise. J Appl Physiol 67:116–122

    PubMed  CAS  Google Scholar 

  • Burke LM, Hawley JA, Wong SH, Jeukendrup AE (2011) Carbohydrates for training and competition. J Sports Sci 29(Suppl 1):S17–S27

    PubMed  Article  Google Scholar 

  • Civitarese AE, Carling S, Heilbronn LK, Hulver MH, Ukropcova B, Deutsch WA, Smith SR, Ravussin E (2007) Calorie restriction increases muscle mitochondrial biogenesis in healthy humans. PLoS Med 4:e76

    PubMed  Article  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 99:1359–1363

    PubMed  Article  CAS  Google Scholar 

  • Cochran AJ, Little JP, Tarnopolsky MA, Gibala MJ (2010) Carbohydrate feeding during recovery alters the skeletal muscle metabolic response to repeated sessions of high-intensity interval exercise in humans. J Appl Physiol 108:628–636

    PubMed  Article  CAS  Google Scholar 

  • Egan B, Carson BP, Garcia-Roves PM, Chibalin AV, Sarsfield FM, Barron N, McCaffrey N, Moyna NM, Zierath JR, O’Gorman DJ (2010) 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 588:1779–1790

    PubMed  Article  CAS  Google Scholar 

  • Finley LW, Lee J, Souza A, Desquiret-Dumas V, Bullock K, Rowe GC, Procaccio V, Clish CB, Arany Z, Haigis MC (2012) Skeletal muscle transcriptional coactivator PGC-1alpha mediates mitochondrial, but not metabolic, changes during calorie restriction. Proc Natl Acad Sci USA 109:2931–2936

    PubMed  Article  CAS  Google Scholar 

  • Garcia-Roves P, Huss JM, Han DH, Hancock CR, Iglesias-Gutierrez E, Chen M, Holloszy JO (2007) Raising plasma fatty acid concentration induces increased biogenesis of mitochondria in skeletal muscle. Proc Natl Acad Sci USA 104:10709–10713

    PubMed  Article  CAS  Google Scholar 

  • Gibala MJ, McGee SL, Garnham AP, Howlett KF, Snow RJ, Hargreaves M (2009) Brief intense interval exercise activates AMPK and p38 MAPK signaling and increases the expression of PGC-1alpha in human skeletal muscle. J Appl Physiol 106:929–934

    PubMed  Article  CAS  Google Scholar 

  • Gleyzer N, Vercauteren K, Scarpulla RC (2005) Control of mitochondrial transcription specificity factors (TFB1M and TFB2M) by nuclear respiratory factors (NRF-1 and NRF-2) and PGC-1 family coactivators. Mol Cell Biol 25:1354–1366

    PubMed  Article  CAS  Google Scholar 

  • Hancock CR, Han DH, Higashida K, Kim SH, Holloszy JO (2011) Does calorie restriction induce mitochondrial biogenesis? A reevaluation. FASEB J 25:785–791

    PubMed  Article  CAS  Google Scholar 

  • Hansen AK, Fischer CP, Plomgaard P, Andersen JL, Saltin B, Pedersen BK (2005) Skeletal muscle adaptation: training twice every second day vs. training once daily. J Appl Physiol 98:93–99

    PubMed  Article  Google Scholar 

  • Harris RC, Hultman E, Nordesjo LO (1974) Glycogen, glycolytic intermediates and high-energy phosphates determined in biopsy samples of musculus quadriceps femoris of man at rest. Methods and variance of values. Scand J Clin Lab Invest 33:109–120

    PubMed  Article  CAS  Google Scholar 

  • Hoeks J, Hesselink MK, Russell AP, Mensink M, Saris WH, Mensink RP, Schrauwen P (2006) Peroxisome proliferator-activated receptor-gamma coactivator-1 and insulin resistance: acute effect of fatty acids. Diabetologia 49:2419–2426

    PubMed  Article  CAS  Google Scholar 

  • Holloszy JO (2008) Regulation by exercise of skeletal muscle content of mitochondria and GLUT4. J Physiol Pharmacol 59(Suppl 7):5–18

    PubMed  Google Scholar 

  • Hulston CJ, Venables MC, Mann CH, Martin C, Philp A, Baar K, Jeukendrup AE (2010) Training with low muscle glycogen enhances fat metabolism in well-trained cyclists. Med Sci Sports Exerc 42:2046–2055

    PubMed  Article  CAS  Google Scholar 

  • Irrcher I, Ljubicic V, Hood DA (2009) Interactions between ROS and AMP kinase activity in the regulation of PGC-1alpha transcription in skeletal muscle cells. Am J Physiol Cell Physiol 296:C116–C123

    PubMed  Article  CAS  Google Scholar 

  • Jager S, Handschin C, St-Pierre J, Spiegelman BM (2007) AMP-activated protein kinase (AMPK) action in skeletal muscle via direct phosphorylation of PGC-1alpha. Proc Natl Acad Sci USA 104:12017–12022

    PubMed  Article  Google Scholar 

  • Ji LL (1993) Antioxidant enzyme response to exercise and aging. Med Sci Sports Exerc 25:225–231

    PubMed  CAS  Google Scholar 

  • Jiang N, Zhang G, Bo H, Qu J, Ma G, Cao D, Wen L, Liu S, Ji LL, Zhang Y (2009) Upregulation of uncoupling protein-3 in skeletal muscle during exercise: a potential antioxidant function. Free Radic Biol Med 46:138–145

    PubMed  Article  CAS  Google Scholar 

  • Kang C, O’Moore KM, Dickman JR, Ji LL (2009) Exercise activation of muscle peroxisome proliferator-activated receptor-gamma coactivator-1alpha signaling is redox sensitive. Free Radic Biol Med 47:1394–1400

    PubMed  Article  CAS  Google Scholar 

  • Katz A (2007) Modulation of glucose transport in skeletal muscle by reactive oxygen species. J Appl Physiol 102:1671–1676

    PubMed  Article  CAS  Google Scholar 

  • Leick L, Plomgaard P, Gronlokke L, Al-Abaiji F, Wojtaszewski JF, Pilegaard H (2010) Endurance exercise induces mRNA expression of oxidative enzymes in human skeletal muscle late in recovery. Scand J Med Sci Sports 20:593–599

    PubMed  Article  CAS  Google Scholar 

  • Lin J, Handschin C, Spiegelman BM (2005) Metabolic control through the PGC-1 family of transcription coactivators. Cell Metab 1:361–370

    PubMed  Article  Google Scholar 

  • Lira VA, Benton CR, Yan Z, Bonen A (2010) PGC-1alpha regulation by exercise training and its influences on muscle function and insulin sensitivity. Am J Physiol Endocrinol Metab 299:E145–E161

    PubMed  CAS  Google Scholar 

  • Little JP, Safdar A, Cermak N, Tarnopolsky MA, Gibala MJ (2010) Acute endurance exercise increases the nuclear abundance of PGC-1alpha in trained human skeletal muscle. Am J Physiol Regul Integr Comp Physiol 298:R912–R917

    PubMed  Article  CAS  Google Scholar 

  • Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 25:402–408

    PubMed  Article  CAS  Google Scholar 

  • Mathai AS, Bonen A, Benton CR, Robinson DL, Graham TE (2008) Rapid exercise-induced changes in PGC-1alpha mRNA and protein in human skeletal muscle. J Appl Physiol 105:1098–1105

    PubMed  Article  CAS  Google Scholar 

  • Molnar AM, Servais S, Guichardant M, Lagarde M, Macedo DV, Pereira-Da-Silva L, Sibille B, Favier R (2006) Mitochondrial H2O2 production is reduced with acute and chronic eccentric exercise in rat skeletal muscle. Antioxid Redox Signal 8:548–558

    PubMed  Article  CAS  Google Scholar 

  • Morton JP, Croft L, Bartlett JD, Maclaren DP, Reilly T, Evans L, McArdle A, Drust B (2009) Reduced carbohydrate availability does not modulate training-induced heat shock protein adaptations but does upregulate oxidative enzyme activity in human skeletal muscle. J Appl Physiol 106:1513–1521

    PubMed  Article  CAS  Google Scholar 

  • Narkar VA, Downes M, Yu RT, Embler E, Wang YX, Banayo E, Mihaylova MM, Nelson MC, Zou Y, Juguilon H, Kang H, Shaw RJ, Evans RM (2008) AMPK and PPARdelta agonists are exercise mimetics. Cell 134:405–415

    PubMed  Article  CAS  Google Scholar 

  • Nordsborg NB, Lundby C, Leick L, Pilegaard H (2010) Relative workload determines exercise-induced increases in PGC-1alpha mRNA. Med Sci Sports Exerc 42:1477–1484

    PubMed  Article  CAS  Google Scholar 

  • Norrbom J, Sundberg CJ, Ameln H, Kraus WE, Jansson E, Gustafsson T (2004) PGC-1alpha mRNA expression is influenced by metabolic perturbation in exercising human skeletal muscle. J Appl Physiol 96:189–194

    PubMed  Article  CAS  Google Scholar 

  • Olesen J, Kiilerich K, Pilegaard H (2010) PGC-1alpha-mediated adaptations in skeletal muscle. Pflugers Arch 460:153–162

    PubMed  Article  CAS  Google Scholar 

  • Pilegaard H, Keller C, Steensberg A, Helge JW, Pedersen BK, Saltin B, Neufer Section Sign PD (2002) Influence of pre-exercise muscle glycogen content on exercise-induced transcriptional regulation of metabolic genes. J Physiol 541:261–271

    Google Scholar 

  • Pilegaard H, Saltin B, Neufer PD (2003) Exercise induces transient transcriptional activation of the PGC-1alpha gene in human skeletal muscle. J Physiol 546:851–858

    PubMed  Article  CAS  Google Scholar 

  • Pilegaard H, Osada T, Andersen LT, Helge JW, Saltin B, Neufer PD (2005) Substrate availability and transcriptional regulation of metabolic genes in human skeletal muscle during recovery from exercise. Metabolism 54:1048–1055

    PubMed  Article  CAS  Google Scholar 

  • Powers SK, Nelson WB, Hudson MB (2011) Exercise-induced oxidative stress in humans: cause and consequences. Free Radic Biol Med 51:942–950

    PubMed  Article  CAS  Google Scholar 

  • Psilander N, Wang L, Westergren J, Tonkonogi M, Sahlin K (2010) Mitochondrial gene expression in elite cyclists: effects of high-intensity interval exercise. Eur J Appl Physiol 110:597–606

    PubMed  Article  Google Scholar 

  • Russell AP, Hesselink MK, Lo SK, Schrauwen P (2005) Regulation of metabolic transcriptional co-activators and transcription factors with acute exercise. FASEB J 19:986–988

    PubMed  CAS  Google Scholar 

  • Tsintzas K, Jewell K, Kamran M, Laithwaite D, Boonsong T, Littlewood J, Macdonald I, Bennett A (2006) Differential regulation of metabolic genes in skeletal muscle during starvation and refeeding in humans. J Physiol 575:291–303

    PubMed  Article  CAS  Google Scholar 

  • Wang L, Psilander N, Tonkonogi M, Ding S, Sahlin K (2009) Similar expression of oxidative genes after interval and continuous exercise. Med Sci Sports Exerc 41:2136–2144

    PubMed  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

    Google Scholar 

  • Watt MJ, Southgate RJ, Holmes AG, Febbraio MA (2004) 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 33:533–544

    PubMed  Article  CAS  Google Scholar 

  • Wojtaszewski JF, MacDonald C, Nielsen JN, Hellsten Y, Hardie DG, Kemp BE, Kiens B, Richter EA (2003) Regulation of 5’AMP-activated protein kinase activity and substrate utilization in exercising human skeletal muscle. Am J Physiol Endocrinol Metab 284:E813–E822

    PubMed  CAS  Google Scholar 

  • Yeo WK, Paton CD, Garnham AP, Burke LM, Carey AL, Hawley JA (2008) Skeletal muscle adaptation and performance responses to once a day versus twice every second day endurance training regimens. J Appl Physiol 105:1462–1470

    PubMed  Article  CAS  Google Scholar 

  • Yeo WK, McGee SL, Carey AL, Paton CD, Garnham AP, Hargreaves M, Hawley JA (2010) Acute signalling responses to intense endurance training commenced with low or normal muscle glycogen. Exp Physiol 95:351–358

    PubMed  Article  CAS  Google Scholar 

Download references

Acknowledgments

The study was supported by grants from the Swedish National Centre for Research in Sports, the Swedish Research Council and the Swedish School of Sport and Health Sciences, Stockholm, Sweden. We thank all the participants for their time and effort. We also gratefully acknowledge Marjan Pontén for her excellent technical assistance. No conflicts of interest, financial or otherwise, are declared by the authors.

Author information

Authors and Affiliations

  1. The Åstrand Laboratory of Work Physiology, GIH, The Swedish School of Sport and Health Sciences, Box 5626, 114 86, Stockholm, Sweden

    Niklas Psilander, Per Frank, Mikael Flockhart & Kent Sahlin

  2. Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden

    Niklas Psilander, Per Frank & Kent Sahlin

Authors
  1. Niklas Psilander
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Per Frank
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mikael Flockhart
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kent Sahlin
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Niklas Psilander.

Additional information

Communicated by Martin Flueck.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

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

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00421-012-2504-8

Keywords

  • Train low
  • Carbohydrate restriction
  • Gene expression
  • PGC-1α
  • Oxidative stress