Skip to main content
SpringerLink
Log in

Metabolomics investigation of exercise-modulated changes in metabolism in rat liver after exhaustive and endurance exercises

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

Abstract

Exhaustive exercise and endurance exercise training modify the physiological status of the body differently. The present study aimed to evaluate the alteration in biochemical composition with exhaustive and endurance exercises in rats using metabolomics strategy. The metabolite profile of liver tissue was investigated on gas chromatography–mass spectrometry (GC–MS). Data further underwent partial least-squares-discriminant analysis (PLS-DA) to compare the effects on metabolites in sedentary control, exhaustively exercised and endurance trained rats. GC–MS detected 115 highly reproducible peaks in chromatograms from individual liver tissue extracts, and we identified 55 of them. The three groups showed significant differences in metabolic profile. Changes in liver metabolism involved metabolites such as amino acids, fatty acids, organic acids, and carbohydrates. Endurance training elevated the greater rate of tricarboxylic acid cycle and antioxidant activity, and exhaustive exercise led to accumulated urea markers and an inflammation response in liver. In addition, GC–MS-based metabolomic analysis is a promising tool to investigate a pathological status with different exercise programs.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  • Baldwin KM, Fitts RH, Booth FW, Winder WW, Holloszy JO (1975) Depletion of muscle and liver glycogen during exercise. Protective effect of training. Pflugers Arch 354:203–212

    Article  CAS  PubMed  Google Scholar 

  • Bedford TG, Tipton CM, Wilson NC, Oppliger RA, Gisolfi CV (1979) Maximum oxygen consumption of rats and its changes with various experimental procedures. J Appl Physiol 47:1278–1283

    CAS  PubMed  Google Scholar 

  • Bloomer RJ (2008) Effect of exercise on oxidative stress biomarkers. Adv Clin Chem 46:1–50

    Article  CAS  PubMed  Google Scholar 

  • Bray MS, Hagberg JM, Pérusse L, Rankinen T, Roth SM, Wolfarth B, Bouchard C (2009) The human gene map for performance and health-related fitness phenotypes: the 2006–2007 update. Med Sci Sports Exerc 41:35–73

    PubMed  Google Scholar 

  • Burniston JG (2008) Changes in the rat skeletal muscle proteome induced by moderate-intensity endurance exercise. Biochim Biophys Acta 1784:1077–1086

    CAS  PubMed  Google Scholar 

  • Chan EC, Koh PK, Mal M, Cheah PY, Eu KW, Backshall A, Cavill R, Nicholson JK, Keun HC (2009) Metabolic profiling of human colorectal cancer using high-resolution magic angle spinning nuclear magnetic resonance (HR-MAS NMR) spectroscopy and gas chromatography mass spectrometry (GC/MS). J Proteome Res 8:352–361

    Article  CAS  PubMed  Google Scholar 

  • Chorell E, Moritz T, Branth S, Antti H, Svensson MB (2009) Predictive metabolomics evaluation of nutrition-modulated metabolic stress responses in human blood serum during the early recovery phase of strenuous physical exercise. J Proteome Res 8:2966–2977

    Article  CAS  PubMed  Google Scholar 

  • Davies KJ, Quintanilha AT, Brooks GA, Packer L (1982) Free radicals and tissue damage produced by exercise. Biochem Biophys Res Commun 107:1198–1205

    Article  CAS  PubMed  Google Scholar 

  • Eberlein M, Scheibner KA, Black KE, Collins SL, Chan-Li Y, Powell JD, Horton MR (2008) Anti-oxidant inhibition of hyaluronan fragment-induced inflammatory gene expression. J Inflamm (Lond) 5:20–30

    Article  Google Scholar 

  • Ellis DI, Dunn WB, Griffin JL, Allwood JW, Goodacre R (2007) Metabolic fingerprinting as a diagnostic tool. Pharmacogenomics 8:1243–1266

    Article  CAS  PubMed  Google Scholar 

  • Fiehn O (2002) Metabolomics—the link between genotypes and phenotypes. Plant Mol Biol 48:155–171

    Article  CAS  PubMed  Google Scholar 

  • Fiehn O, Kopka J, Dörmann P, Altmann T, Trethewey RN, Willmitzer L (2000) Metabolite profiling for plant functional genomics. Nat Biotechnol 18:1157–1161

    Article  CAS  PubMed  Google Scholar 

  • Gill JM, Cooper AR (2008) Physical activity and prevention of type 2 diabetes mellitus. Sports Med 38:807–824

    Article  PubMed  Google Scholar 

  • Gill JM, Hardman AE (2003) Exercise and postprandial lipid metabolism: an update on potential mechanisms and interactions with high-carbohydrate diets. J Nutr Biochem 14:122–132

    Article  CAS  PubMed  Google Scholar 

  • Gomez-Cabrera MC, Domenech E, Viña J (2008) Moderate exercise is an antioxidant: upregulation of antioxidant genes by training. Free Radic Biol Med 44:126–131

    Article  CAS  PubMed  Google Scholar 

  • Gutteridge JM (1999) Redox imbalance in the critically ill. Br Med Bull 55:49–75

    Article  CAS  PubMed  Google Scholar 

  • Hellsten Y, Frandsen U, Orthenblad N, Sjødin B, Richter EA (1997) Xanthine oxidase in human skeletal muscle following eccentric exercise: a role in inflammation. J Physiol 498:239–248

    CAS  PubMed  Google Scholar 

  • Huang CC, Tsai SC, Lin WT (2008) Potential ergogenic effects of l-arginine against oxidative and inflammatory stress induced by acute exercise in aging rats. Exp Gerontol 43:571–577

    Article  CAS  PubMed  Google Scholar 

  • Idle JR, Gonzalez FJ (2007) Metabolomics. Cell Metab 6:348–351

    Article  CAS  PubMed  Google Scholar 

  • Lee SH, Woo HM, Jung BH, Lee J, Kwon OS, Pyo HS, Choi MH, Chung BC (2007) Metabolomic approach to evaluate the toxicological effects of nonylphenol with rat urine. Anal Chem 79:6102–6110

    Article  CAS  PubMed  Google Scholar 

  • Leeuwenburgh C, Ji LL (1995) Glutathione depletion in rested and exercised mice: biochemical consequence and adaptation. Arch Biochem Biophys 316:941–949

    Article  CAS  PubMed  Google Scholar 

  • Li X, Xu Z, Lu X, Yang X, Yin P, Kong H, Yu Y, Xu G (2009) Comprehensive two-dimensional gas chromatography/time-of -flight mass spectrometry for metabonomics: biomarker discovery for diabetes mellitus. Anal Chim Acta 633:257–262

    Article  CAS  PubMed  Google Scholar 

  • Lin WT, Yang SC, Tsai SC, Huang CC, Lee NY (2006) l-Arginine attenuates xanthine oxidase and myeloperoxidase activities in hearts of rats during exhaustive exercise. Br J Nutr 95:67–75

    Article  CAS  PubMed  Google Scholar 

  • Litvinova L, Viru A (1995) Effect of exercise and adrenal insufficiency on urea production in rat. Eur J Appl Physiol 70:536–540

    Article  CAS  Google Scholar 

  • Liu CC, Huang CC, Lin WT, Hsieh CC, Huang SY, Lin SJ, Yang SC (2005) Lycopene supplementation attenuated xanthine oxidase and myeloperoxidase activities in skeletal muscle tissues of rats after exhaustive exercise. Br J Nutr 94:595–601

    Article  CAS  PubMed  Google Scholar 

  • Mooren FC, Blöming D, Lechtermann A, Lerch MM, Völker K (2002) Lymphocyte apoptosis after exhaustive and moderate exercise. J Appl Physiol 93:147–153

    CAS  PubMed  Google Scholar 

  • Mougios V (2006) Exercise biochemistry. Human kinetics, Champaign, pp 129-131

  • Oztasan N, Taysi S, Gumustekin K, Altinkaynak K, Aktas O, Timur H, Siktar E, Keles S, Akar S, Akcay F, Dane S, Gul M (2004) Endurance training attenuates exercise-induced oxidative stress in erythrocytes in rat. Eur J Appl Physiol 91:622–627

    Article  CAS  PubMed  Google Scholar 

  • Poortmans JR (1988) Protein metabolism. In: Poortmans JRP (ed) Principles of exercise biochemistry. Karger, Basel, pp 164–193

    Google Scholar 

  • Powers SK, Jackson MJ (2008) Exercise-induced oxidative stress: cellular mechanisms and impact on muscle force production. Physiol Rev 88:1243–1276

    Article  CAS  PubMed  Google Scholar 

  • Radák Z, Asano K, Inoue M, Kizaki T, Oh-Ishi S, Suzuki K, Taniguchi N, Ohno H (1995) Superoxide dismutase derivative reduces oxidative damage in skeletal muscle of rats during exhaustive exercise. J Appl Physiol 79:129–135

    PubMed  Google Scholar 

  • Shyur LF, Huang CC, Lo CP, Chiu CY, Chen YP, Wang SY, Chang ST (2008) Hepatoprotective phytocompounds from Cryptomeria japonica are potent modulators of inflammatory mediators. Phytochemistry 69:1348–1358

    Article  CAS  PubMed  Google Scholar 

  • Skenderi KP, Tsironi M, Lazaropoulou C, Anastasiou CA, Matalas AL, Kanavaki I, Thalmann M, Goussetis E, Papassotiriou I, Chrousos GP (2008) Changes in free radical generation and antioxidant capacity during ultramarathon foot race. Eur J Clin Invest 38:159–165

    Article  CAS  PubMed  Google Scholar 

  • Smolka MB, Zoppi CC, Alves AA, Silveira LR, Marangoni S, Pereira-Da-Silva L, Novello JC, Macedo DV (2000) HSP72 as a complementary protection against oxidative stress induced by exercise in the soleus muscle of rats. Am J Physiol Regul Integr Comp Physiol 279:R1539–R1545

    CAS  PubMed  Google Scholar 

  • Suzuki K, Nakaji S, Yamada M, Totsuka M, Sato K, Sugawara K (2002) Systemic inflammatory response to exhaustive exercise. Cytokine kinetics. Exerc Immunol Rev 8:6–48

    PubMed  Google Scholar 

  • Tanimura Y, Shimizu K, Tanabe K, Otsuki T, Yamauchi R, Matsubara Y, Iemitsu M, Maeda S, Ajisaka R (2008) Exercise-induced oxidative DNA damage and lymphocytopenia in sedentary young males. Med Sci Sports Exerc 40:1455–1462

    Article  CAS  PubMed  Google Scholar 

  • Thompson PD, Franklin BA, Balady GJ, Blair SN, Corrado D, Estes NA 3rd, Fulton JE, Gordon NF, Haskell WL, Link MS, Maron BJ, Mittleman MA, Pelliccia A, Wenger NK, Willich SN, Costa F; American Heart Association Council on Nutrition, Physical Activity, and Metabolism; American Heart Association Council on Clinical Cardiology; American College of Sports Medicine (2007) Exercise and acute cardiovascular events placing the risks into perspective: a scientific statement from the American Heart Association Council on Nutrition, Physical Activity, and Metabolism and the Council on Clinical Cardiology. Circulation 115:2358–2368

    Google Scholar 

  • Tsai K, Hsu TG, Hsu KM, Cheng H, Liu TY, Hsu CF, Kong CW (2001) Oxidative DNA damage in human peripheral leukocytes induced by massive aerobic exercise. Free Radic Biol Med 31:1465–1472

    Article  CAS  PubMed  Google Scholar 

  • Viña J, Gimeno A, Sastre J, Desco C, Asensi M, Pallardó FV, Cuesta A, Ferrero JA, Terada LS, Repine JE (2000a) Mechanism of free radical production in exhaustive exercise in humans and rats; role of xanthine oxidase and protection by allopurinol. IUBMB Life 49:539–544

    Article  PubMed  Google Scholar 

  • Viña J, Gomez-Cabrera MC, Lloret A, Marquez R, Miñana JB, Pallardó FV, Sastre J (2000b) Free radicals in exhaustive physical exercise: mechanism of production, and protection by antioxidants. IUBMB Life 50:271–277

    Article  PubMed  Google Scholar 

  • Viru A (1987) Metabolization of structural proteins during exercise. Sports Med 4:95–128

    Article  CAS  PubMed  Google Scholar 

  • Vollaard NB, Shearman JP, Cooper CE (2005) Exercise-induced oxidative stress: myths, realities and physiological relevance. Sports Med 35:1045–1062

    Article  PubMed  Google Scholar 

  • Woo HM, Kim KM, Choi MH, Jung BH, Lee J, Kong G, Nam SJ, Kim S, Bai SW, Chung BC (2009) Mass spectrometry based metabolomic approaches in urinary biomarker study of women’s cancers. Clin Chim Acta 400:63–69

    Article  CAS  PubMed  Google Scholar 

  • Yan B, A J, Wang G, Lu H, Huang X, Liu Y, Zha W, Hao H, Zhang Y, Liu L, Gu S, Huang Q, Zheng Y, Sun J (2009) Metabolomic investigation into variation of endogenous metabolites in professional athletes subject to strength-endurance training. J Appl Physiol 106:531–538

    Google Scholar 

Download references

Acknowledgments

This study was supported by the National Science Council of Taiwan (NSC-97-2410-H029-037-MY2). The authors thank the Metabolomics Core Facility (Agricultural Biotechnology Research Center, Academia Sinica) for GC–MS analysis. We also thank Laura Heraty for her careful reading of the manuscript.

Author information

Authors and Affiliations

  1. Agricultural Biotechnology Research Center, Academia Sinica, No. 128, Sec. 2, Academia Road, Nankang, Taipei, 11529, Taiwan, ROC

    Chi-Chang Huang, Pi-Wen Tsai & Chia-Chung Hou

  2. Department of Hospitality Management, College of Agriculture, Tunghai University, Taichung, 40704, Taiwan, ROC

    Wan-Teng Lin

  3. Graduate Institute of Pharmacognosy Science, Taipei Medical University, Taipei, 11031, Taiwan, ROC

    Feng-Lin Hsu

Authors
  1. Chi-Chang Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Wan-Teng Lin
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Feng-Lin Hsu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Pi-Wen Tsai
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Chia-Chung Hou
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Chia-Chung Hou.

Additional information

Communicated by Susan Ward.

C.-C. Huang and W.-T. Lin contributed equally and appear in alphabetical order.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Huang, CC., Lin, WT., Hsu, FL. et al. Metabolomics investigation of exercise-modulated changes in metabolism in rat liver after exhaustive and endurance exercises. Eur J Appl Physiol 108, 557–566 (2010). https://doi.org/10.1007/s00421-009-1247-7

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00421-009-1247-7

Keywords

Search

Navigation