Abstract
The study examines plasma metabolic profiles of patients with chronic obstructive pulmonary disease (COPD) to prove whether the disease influences metabolism at rest and after endurance training. This is based on the hypothesis that metabolome levels should reflect impaired skeletal muscle bioenergetics in COPD. The study aims to test this hypothesis by evaluating plasma metabolic profiles in COPD patients before and after 8 weeks of endurance exercise training. We studied blood samples from 18 COPD patients and 12 healthy subjects. Pre- and post-training blood plasma samples at rest and after constant-work rate exercise (CWRE) at 70% of pre-training Watts peak were analyzed by 1H-nuclear magnetic resonance spectroscopy to assess metabolite profiles. The two groups presented training-induced physiological changes in the VO2 peak and in blood lactate levels (P < 0.01 each). Before training, the two groups also showed differences in metabolic profiles at rest (P < 0.05). Levels of valine (r = 0.51, P < 0.01), alanine (r = 0.45, P < 0.05) and isoleucine (r = 0.51, P < 0.01) were positively associated with body composition (Fat Free Mass Index). While training showed a significant impact on the metabolic profile in healthy subjects (P < 0.001), with changes in levels of amino acids, creatine, succinate, pyruvate, glucose and lactate (P < 0.05 each), no equivalent training-induced effects were seen in COPD patients in whom only lactate decreased (P < 0.05). This study shows that plasma metabolic profiling contributes to the phenotypic characterization of COPD patients.
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Aue, W. P., Karhan, J., & Ernst, R. R. (1976). Homonuclear broad band decoupling and two-dimensional J-resolved NMR spectroscopy. Journal of Chemical Physics, 64, 4226–4227.
Bolton, C. E., Broekhuizen, R., Ionescu, A. A., et al. (2007). Cellular protein breakdown and systemic inflammation are unaffected by pulmonary rehabilitation in COPD. Thorax, 62(2), 109–114.
Chan, E. C., Koh, P. K., Mal, M., et al. (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). Journal of Proteome Research, 8(1), 352–361.
Deutz, N. E., Wagenmakers, A. J., & Soeters, P. B. (1999). Discrepancy between muscle and whole body protein turnover. Current opinion in clinical nutrition and metabolic care, 2(1), 29–32.
Engelen, M. P., Schols, A. M., Does, J. D., et al. (2000). Exercise-induced lactate increase in relation to muscle substrates in patients with chronic obstructive pulmonary disease. American Journal of Respiratory and Critical Care medicine, 162(5), 1697–1704.
Engelen, M. P., Wouters, E. F., Deutz, N. E., et al. (2001). Effects of exercise on amino acid metabolism in patients with chronic obstructive pulmonary disease. American Journal of Respiratory and Critical Care medicine, 163(4), 859–864.
Green, H. J., Bombardier, E., Burnett, M., et al. (2008a). Organization of metabolic pathways in vastus lateralis of patients with chronic obstructive pulmonary disease. American Journal of Physiology–Regulatory, Integrative and Comparative Physiology, 295(3), R935–R941.
Green, H. J., Burnett, M. E., D’Arsigny, C. L., et al. (2008b). Altered metabolic and transporter characteristics of vastus lateralis in chronic obstructive pulmonary disease. Journal of Applied Physiology, 105(3), 879–886.
Gunther, U. L., Ludwig, C., & Ruterjans, H. (2000). NMRLAB-Advanced NMR data processing in matlab. Journal of Magnetic Resonance, 145(2), 201–208.
Haller, R. G., Henriksson, K. G., Jorfeldt, L., et al. (1991). Deficiency of skeletal muscle succinate dehydrogenase and aconitase. Pathophysiology of exercise in a novel human muscle oxidative defect. Journal of Clinical Investigation, 88(4), 1197–1206.
Hansford, R. G., Hogue, B. A., & Mildaziene, V. (1997). Dependence of H2O2 formation by rat heart mitochondria on substrate availability and donor age. Journal of Bioenergy and Biomembrane, 29(1), 89–95.
Holmes, E., Wilson, I. D., & Nicholson, J. K. (2008). Metabolic phenotyping in health and disease. Cell, 134(5), 714–717.
Hwang, T. L., & Shaka, A. J. (1995). Water suppression that works. excitation sculpting using arbitrary waveforms and pulsed field gradients. Journal of Magnetic Resonance, A112, 235–239.
Kargotich, S., Keast, D., Goodman, C., et al. (2007). Monitoring 6 weeks of progressive endurance training with plasma glutamine. International Journal of Sports Medicine, 28(3), 211–216.
Keun, H. C. (2007). Biomarker discovery for drug development and translational medicine using metabonomics. Ernst Schering Foundation Symposium Proceedings, (4), 79–98.
Kuo, C. D., Wu, W. G., Wang, J. H., et al. (1989). Proton nuclear magnetic resonance studies of plasma to determine metabolic status of patients with adult respiratory distress syndrome. Clinical Chemistry, 35(4), 667–670.
Kutsuzawa, T., Shioya, S., Kurita, D., et al. (2009). Plasma branched-chain amino acid levels and muscle energy metabolism in patients with chronic obstructive pulmonary disease. Clinical Nutrition, 28(2), 203–208.
Langen, R. C., Schols, A. M., Kelders, M. C., et al. (2001). Inflammatory cytokines inhibit myogenic differentiation through activation of nuclear factor-kappaB. FASEB J., 15(7), 1169–1180.
Maltais, F., LeBlanc, P., Jobin, J., et al. (1997). Intensity of training and physiologic adaptation in patients with chronic obstructive pulmonary disease. American Journal of Respiratory and Critical Care Medicine, 155(2), 555–561.
Maltais, F., Simard, A. A., Simard, C., et al. (1996). Oxidative capacity of the skeletal muscle and lactic acid kinetics during exercise in normal subjects and in patients with COPD. American Journal of Respiratory and Critical Care Medicine, 153(1), 288–293.
Morrison, W. L., Gibson, J. N., Scrimgeour, C., et al. (1988). Muscle wasting in emphysema. Clinical Science (London), 75(4), 415–420.
Newsholme, E. A., & Parry-Billings, M. (1990). Properties of glutamine release from muscle and its importance for the immune system. JPEN Journal of Parenteral and Enteral Nutrition, 14(4 Suppl), 63S–67S.
Nicholson, J. K., & Lindon, J. C. (2008). Systems biology: Metabonomics. Nature, 455(7216), 1054–1056.
Nici, L., Donner, C., Wouters, E., et al. (2006). American thoracic society/european respiratory society statement on pulmonary rehabilitation. American Journal of Respiratory and Critical Care Medicine, 173(12), 1390–1413.
Puente-Maestu, L., Perez-Parra, J., Godoy, R., et al. (2009). Abnormal mitochondrial function in locomotor and respiratory muscles of COPD patients. The European Respiratory Journal, 33(5), 1045–1052.
Rabinovich, R. A., Ardite, E., Troosters, T., et al. (2001). Reduced muscle redox capacity after endurance training in patients with chronic obstructive pulmonary disease. American Journal of Respiratory and Critical Care Medicine, 164(7), 1114–1118.
Rabinovich, R. A., Bastos, R., Ardite, E., et al. (2007). Mitochondrial dysfunction in COPD patients with low body mass index. The European Respiratory Journal, 29(4), 643–650.
Rutten, E. P., Engelen, M. P., Wouters, E. F., et al. (2006a). Effect of glutamate ingestion on whole-body glutamate turnover in healthy elderly and patients with chronic obstructive pulmonary disease. Nutrition, 22(5), 496–503.
Rutten, E. P., Engelen, M. P., Wouters, E. F., et al. (2006b). Metabolic effects of glutamine and glutamate ingestion in healthy subjects and in persons with chronic obstructive pulmonary disease. The American Journal of Clinical Nutrition, 83(1), 115–123.
Rutten, E. P., Franssen, F. M., Engelen, M. P., et al. (2006c). Greater whole-body myofibrillar protein breakdown in cachectic patients with chronic obstructive pulmonary disease. The American Journal of Clinical Nutrition, 83(4), 829–834.
Sala, E., Roca, J., Marrades, R. M., et al. (1999). Effects of endurance training on skeletal muscle bioenergetics in chronic obstructive pulmonary disease. American Journal of Respiratory and Critical Care Medicine, 159(6), 1726–1734.
Thrippleton, M. J., Edden, R. A., & Keeler, J. (2005). Suppression of strong coupling artefacts in J-spectra. Journal of Magnetic Resonance, 174(1), 97–109.
Tiziani, S., Emwas, A. H., Lodi, A., et al. (2008). Optimized metabolite extraction from blood serum for 1H nuclear magnetic resonance spectroscopy. Analytical Biochemistry, 377(1), 16–23.
Tiziani, S., Lodi, A., Khanim, F. L., et al. (2009). Metabolomic profiling of drug responses in acute myeloid leukaemia cell lines. PLoS ONE, 4(1), e4251.
Troosters, T., Casaburi, R., Gosselink, R., et al. (2005). Pulmonary rehabilitation in chronic pulmonary disease. American Journal of Respiratory and Critical Care Medicine, 172(1), 19–38.
Vilaró, J., Gimeno, E., Sanchez Ferez, N., et al. (2007). Daily living activity in chronic obstructive pulmonary disease: validation of the Spanish version and comparative analysis of 2 questionnaires. Medical Clinic (Barcelone)., 129(9), 326–332.
Weljie, A. M., Dowlatabadi, R., Miller, B. J., et al. (2007). An inflammatory arthritis-associated metabolite biomarker pattern revealed by 1H NMR spectroscopy. Journal of Proteome Research, 6(9), 3456–3464.
Wouters, E. F. (2000). Nutrition and metabolism in COPD. Chest, 117(5 Suppl 1), 274S–280S.
Acknowledgments
The authors thank the contribution of Elena Gimeno, Jordi Vilaro, Phillip Muñoz, Yolanda Torralba and all the technical staff of the Lung Function Laboratory for their collaboration in the physiological studies and during the training program. This study was supported by European Commission (FP6) BIOBRIDGE (LSHG-CT-2006-037939.); Fundació Marató TV3-042010 Fondo de Investigaciones Sanitarias (FIS-PI061510); CIBERES (CB-06/06), ISCIII-RTICC (RD06/0020/0046); Comissionat per a Universitats i Recerca de la Generalitat de Catalunya (2009SGR1308 and 2009SGR911), and Icrea Academia award 2010 granted to M. Cascante, and Spanish Government Ministry of Science and Innovation and the European Union FEDER funds (SAF2008-00164). Financial support was also given by the Access to Research Infrastructures activity in the 6th Framework Program of the EC (Contract# RII3-026145, EU-NMR) for obtaining NMR spectra at HWB-NMR.
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Diego A. Rodríguez and Gema Alcarraz-Vizán contributed equally to this work.
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Rodríguez, D.A., Alcarraz-Vizán, G., Díaz-Moralli, S. et al. Plasma metabolic profile in COPD patients: effects of exercise and endurance training. Metabolomics 8, 508–516 (2012). https://doi.org/10.1007/s11306-011-0336-x
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DOI: https://doi.org/10.1007/s11306-011-0336-x