Physical fitness level is reflected by alterations in the human plasma metabolome.

An excessive energy intake combined with a low level of physical activity induces detrimental processes involved in disease development, e.g. type 2 diabetes and cardiovascular disease. However the underlying mechanisms for regulation of metabolic capacity and fitness status remain unclear. Metabolomics involves global studies of the metabolic reactions in an organism or cell. Thus hypotheses regarding biochemical events can be generated to increase the understanding of disease development and thereby aid in the development of novel treatments or preventions. We present the first standardized intervention study focusing on characterizing the human metabolome in relation to moderate differences in cardiorespiratory fitness. Gas chromatography-time of flight/mass spectrometry (GC-TOF/MS) was used to characterize 460 plasma samples from 27 individuals divided into two groups based on physical fitness level (VO(2)max). Multi- and univariate between group comparisons based on 197 metabolites were carried out in samples collected at rest prior to any intervention, over time following a nutritional load or a standardized exercise scheme, with and without nutritional load. We detected decreased levels of gamma-tocopherol (GT), a vitamin E isomer, in response to a high fitness level, whereas the opposite was seen for the alpha isomer (AT). In addition, the high fitness level was associated with elevated ω3-PUFA (DHA, 22 : 6ω3) and a decrease in ω6-PUFA (18 : 2ω6) as well as in saturated (16 : 0, 18 : 0), monounsaturated (18 : 1) and trans (16 : 1) fatty acids. We thus hypothesize that high fitness status induces an increased cardiorespiratory inflammatory and antioxidant defense system, more prone to deal with the inflammatory response following exercise and nutrition intake.

[1]  S. Powers,et al.  Reactive oxygen and nitrogen species as intracellular signals in skeletal muscle , 2011, The Journal of physiology.

[2]  C. Sensen,et al.  Metabolomic response to exercise training in lean and diet-induced obese mice. , 2011, Journal of applied physiology.

[3]  A. Nordström,et al.  Effects of badminton and ice hockey on bone mass in young males: a 12-year follow-up. , 2010, Bone.

[4]  Rahul C. Deo,et al.  Metabolic Signatures of Exercise in Human Plasma , 2010, Science Translational Medicine.

[5]  G. Biolo,et al.  Prolonged inactivity up-regulates cholesteryl ester transfer protein independently of body fat changes in humans. , 2010, The Journal of clinical endocrinology and metabolism.

[6]  M. Linden,et al.  Gamma tocopherol supplementation prevents exercise induced coagulation and platelet aggregation. , 2010, Thrombosis research.

[7]  B. K. Pedersen.  The diseasome of physical inactivity – and the role of myokines in muscle–fat cross talk , 2009, The Journal of physiology.

[8]  Brett R. Wenner,et al.  Metabolomics Applied to Diabetes Research , 2009, Diabetes.

[9]  Henrik Antti,et al.  Predictive metabolomics evaluation of nutrition-modulated metabolic stress responses in human blood serum during the early recovery phase of strenuous physical exercise. , 2009, Journal of proteome research.

[10]  M. Kiely,et al.  Cardiovascular risk factors in young, overweight, and obese European adults and associations with physical activity and omega-3 index. , 2009, Nutrition research.

[11]  C. Lavie,et al.  Exercise training and cardiac rehabilitation in primary and secondary prevention of coronary heart disease. , 2009, Mayo Clinic proceedings.

[12]  R. Rauramaa,et al.  The predictive value of cardiorespiratory fitness combined with coronary risk evaluation and the risk of cardiovascular and all‐cause death , 2007, Journal of internal medicine.

[13]  T. Moritz,et al.  A multivariate screening strategy for investigating metabolic effects of strenuous physical exercise in human serum. , 2007, Journal of proteome research.

[14]  Johan Trygg,et al.  Chemometrics in metabonomics. , 2007, Journal of proteome research.

[15]  W. Kraus,et al.  Modest Exercise Prevents the Progressive Disease Associated with Physical Inactivity , 2007, Exercise and sport sciences reviews.

[16]  M. Rantalainen,et al.  OPLS discriminant analysis: combining the strengths of PLS‐DA and SIMCA classification , 2006 .

[17]  M. Febbraio,et al.  Vitamin E isoform-specific inhibition of the exercise-induced heat shock protein 72 expression in humans. , 2006, Journal of applied physiology.

[18]  Johan Lindberg,et al.  Predictive metabolite profiling applying hierarchical multivariate curve resolution to GC-MS data--a potential tool for multi-parametric diagnosis. , 2006, Journal of proteome research.

[19]  J. Trygg,et al.  Extraction and GC/MS analysis of the human blood plasma metabolome. , 2005, Analytical chemistry.

[20]  Johan Trygg,et al.  High-throughput data analysis for detecting and identifying differences between samples in GC/MS-based metabolomic analyses. , 2005, Analytical chemistry.

[21]  D. Kell,et al.  Metabolomics by numbers: acquiring and understanding global metabolite data. , 2004, Trends in biotechnology.

[22]  J. Tur,et al.  Effect of exercise intensity and training on antioxidants and cholesterol profile in cyclists. , 2003, The Journal of nutritional biochemistry.

[23]  E Holmes,et al.  Chemometric contributions to the evolution of metabonomics: mathematical solutions to characterising and interpreting complex biological NMR spectra. , 2002, The Analyst.

[24]  A. Simopoulos.  Omega-3 Fatty Acids in Inflammation and Autoimmune Diseases , 2002, Journal of the American College of Nutrition.

[25]  B. Sjödin,et al.  Adaptive stress response of glutathione and uric acid metabolism in man following controlled exercise and diet. , 2002, Acta physiologica Scandinavica.

[26]  S. Wold,et al.  Orthogonal projections to latent structures (O‐PLS) , 2002 .

[27]  J Bangsbo,et al.  Allantoin formation and urate and glutathione exchange in human muscle during submaximal exercise. , 2001, Free radical biology & medicine.

[28]  S. Wold,et al.  PLS-regression: a basic tool of chemometrics , 2001 .

[29]  Y. Kudo,et al.  Characterization of process-induced lattice distortion in silicon by double-crystal x-ray topography using a curved collimator , 2001 .

[30]  I Mujika,et al.  Cardiorespiratory and metabolic characteristics of detraining in humans. , 2001, Medicine and science in sports and exercise.

[31]  J. Helge,et al.  Training affects muscle phospholipid fatty acid composition in humans. , 2001, Journal of applied physiology.

[32]  K. Häkkinen,et al.  Neuromuscular adaptation during prolonged strength training, detraining and re-strength-training in middle-aged and elderly people , 2000, European Journal of Applied Physiology.

[33]  A. Stocker,et al.  Vitamin E: non-antioxidant roles. , 2000, Progress in lipid research.

[34]  L L Ji,et al.  Antioxidants and oxidative stress in exercise. , 1999, Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine.

[35]  S. Powers,et al.  Exercise training-induced alterations in skeletal muscle antioxidant capacity: a brief review. , 1999, Medicine and science in sports and exercise.

[36]  B. Ames,et al.  γ-Tocopherol traps mutagenic electrophiles such as NOx and complements α-tocopherol: Physiological implications , 1997 .

[37]  J M Venäläinen,et al.  Relation of leisure-time physical activity and cardiorespiratory fitness to the risk of acute myocardial infarction. , 1994, The New England journal of medicine.

[38]  L. Ji,et al.  Responses of glutathione system and antioxidant enzymes to exhaustive exercise and hydroperoxide. , 1992, Journal of applied physiology.

[39]  H. Alessio,et al.  MDA content increases in fast- and slow-twitch skeletal muscle with intensity of exercise in a rat. , 1988, The American journal of physiology.

[40]  J. Weiter,et al.  Oral α-Tocopherol Supplements Decrease Plasma γ-Tocopherol Levels in Humans , 1985 .

[41]  J. Henriksson,et al.  Increase in skeletal muscle lipoprotein lipase following endurance training in man. , 1983, Atherosclerosis.

[42]  B. Saltin,et al.  Effect of training on circulatory response to exercise. , 1968, Journal of applied physiology.

[43]  P. Åstrand,et al.  Training of the oxygen transport system in man. , 1967, Journal of applied physiology.

[44]  B. Commoner,et al.  Free Radicals in Biological Materials , 1954, Nature.

[45]  O. Fiehn.  Metabolomics – the link between genotypes and phenotypes , 2004, Plant Molecular Biology.

[46]  R. Bolli,et al.  New perspectives on vitamin E: γ-tocopherol and carboxyethylhydroxychroman metabolites in biology and medicine , 2004 .

[47]  M. Francaux,et al.  Changes in plasma and urinary taurine and amino acids in runners immediately and 24 h after a marathon , 2001, Amino Acids.

[48]  W. Kohrt,et al.  The regulation of carbohydrate and fat metabolism during and after exercise. , 1998, Frontiers in bioscience : a journal and virtual library.

[49]  K. Davies,et al.  HSP70 and other possible heat shock or oxidative stress proteins are induced in skeletal muscle, heart, and liver during exercise. , 1991, Free radical biology & medicine.