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  • 1.
    Alvehus, Malin
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Boman, Niklas
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Söderlund, Karin
    Svensson, Michael B.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Buren, Jonas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Metabolic adaptations in skeletal muscle, adipose tissue, and whole-body oxidative capacity in response to resistance training2014In: European Journal of Applied Physiology, ISSN 1439-6319, E-ISSN 1439-6327, Vol. 114, no 7, 1463-1471 p.Article in journal (Refereed)
    Abstract [en]

    The effects of resistance training on mitochondrial biogenesis and oxidative capacity in skeletal muscle are not fully characterized, and even less is known about alterations in adipose tissue. We aimed to investigate adaptations in oxidative metabolism in skeletal muscle and adipose tissue after 8 weeks of heavy resistance training in apparently healthy young men. Expression of genes linked to oxidative metabolism in the skeletal muscle and adipose tissue was assessed before and after the training program. Body composition, peak oxygen uptake (VO2 peak), fat oxidation, activity of mitochondrial enzyme in muscle, and serum adiponectin levels were also determined before and after resistance training. In muscle, the expression of the genes AdipoR1 and COX4 increased after resistance training (9 and 13 %, respectively), whereas the expression levels of the genes PGC-1 alpha, SIRT1, TFAM, CPT1b, and FNDC5 did not change. In adipose tissue, the expression of the genes SIRT1 and CPT1b decreased after training (20 and 23 %, respectively). There was an increase in lean mass (from 59.7 +/- A 6.1 to 61.9 +/- A 6.2 kg), VO2 peak (from 49.7 +/- A 5.5 to 56.3 +/- A 5.0 ml/kg/min), and fat oxidation (from 6.8 +/- A 2.1 to 9.1 +/- A 2.7 mg/kg fat-free mass/min) after training, whereas serum adiponectin levels decreased significantly and enzyme activity of citrate synthase and 3-hydroxyacyl-CoA dehydrogenase did not change. Despite significant increases in VO2 peak, fat oxidation, and lean mass following resistance training, the total effect on gene expression and enzyme activity linked to oxidative metabolism was moderate.

  • 2.
    Boman, Niklas
    et al.
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Idrottsmedicin.
    Burén, Jonas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Åkerfeldt, T
    Svensson, Michael B.
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Idrottsmedicin.
    Effects of protein ingestion on the hormonal response to resistance exercise and increases in lean body mass after eight weeks of trainingManuscript (preprint) (Other academic)
  • 3. Burgess, D H
    et al.
    Svensson, M
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Dandrea, T
    Grönlund, K
    Hammarquist, F
    Orrenius, S
    Cotgreave, I A
    Human skeletal muscle cytosols are refractory to cytochrome c-dependent activation of type-II caspases and lack APAF-1.1999In: Cell Death and Differentiation, ISSN 1350-9047, E-ISSN 1476-5403, Vol. 6, no 3, 256-61 p.Article in journal (Refereed)
    Abstract [en]

    Apoptotic regulatory mechanisms in skeletal muscle have not been revealed. This is despite indications that remnant apoptotic events are detected following exercise, muscle injury and the progression of dystrophinopathies. The recent elicitation of a cytochrome c-mediated induction of caspases has led to speculation regarding a cytochrome c mechanism in muscle. We demonstrate that cytosols from skeletal muscle biopsies from healthy human volunteers lack the ability to activate type-II caspases by a cytochrome c-mediated pathway despite the confirmed presence of both procaspase-3 and -9. This was not due to the presence of an endogenous inhibitor, as the muscle cytosols enhanced caspase activity when added to a control cytosol, subsequently activated by cytochrome c and dATP. In addition, we demonstrate that muscle cytosols lack the apoptosis protease activator protein-1 (APAF-1), both at the protein and mRNA levels. These data indicate that human skeletal muscle cells will be refractory to mitochondrial-mediated events leading to apoptosis and thus can escape a major pro-apoptotic regulatory mechanism. This may reflect an evolutionary adaptation of cell survival in the presence of the profusion of mitochondria required for energy generation in motility.

  • 4.
    Chorell, Elin
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Moritz, Thomas
    Branth, Stefan
    Antti, Henrik
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Svensson, Michael
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    A predictive metabolomics evaluation of nutrition-modulated metabolic stress responses in human blood serum during the early recovery phase of strenuous physical exercise2009In: Journal of Proteome Research, ISSN 1535-3893, E-ISSN 1535-3907, Vol. 8, no 6, 2966-77 p.Article in journal (Refereed)
    Abstract [en]

    We have investigated whether postexercise ingestion of carbohydrates in combination with proteins generates a different systemic metabolic response, as compared to the sole ingestion of carbohydrate or water, in the early recovery phase following exercise. In addition, metabolic patterns related to fitness level were studied together with individual responses to nutritional modulation. Twenty-four male subjects were exposed to 90 min of ergometer-cycling. Each participant was subject to four identical test-sessions, including ingestion of one of four beverages (water, low-carbohydrate beverage, high-carbohydrate beverage, and low-carbohydrate−protein beverage (LCHO-P)) immediately after cycling. Blood was collected at six time points, one pre- and five postexercise. Extracted blood serum was subject to metabolomic characterization by gas chromatography/time-of-flight mass spectrometry (GC−TOF MS). Data was processed using hierarchical multivariate curve resolution (HMCR), and multivariate statistical analysis was carried out using orthogonal partial least-squares (OPLS). Predictive metabolomics, including predictive HMCR and OPLS classification, was applied to ensure efficient sample processing and validation of detected metabolic patterns. Separation of subjects in relation to ingested beverage was detected and interpreted. Pseudouridine was suggested as a novel marker for pro-anabolic effect following LCHO-P ingestion, which was supported by the detected decrease of the catabolic marker 3-methylhistidine. Separation of subjects according to fitness level was achieved, and nutritional modulation by LCHO-P was shown to improve the metabolic status of less fit subjects in the recovery phase. In addition, the potential of the methodology for detection of early signs of insulin resistance was also demonstrated.

  • 5.
    Chorell, Elin
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Svensson, Michael
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Moritz, Thomas
    Swedish University of Agricultural Sciences.
    Antti, Henrik
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Physical fitness level is reflected by alterations in the human plasma metabolome2012In: Molecular BioSystems, ISSN 1742-206X, Vol. 8, no 4, 1187-1196 p.Article in journal (Refereed)
    Abstract [en]

    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 (VO2max). 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.

  • 6.
    Chorell, Elin
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Thysell, Elin
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Jonsson, Pär
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Eklund, Caroline
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Silfver, Anders
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Carlsson, Inga-Britt
    Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Lundgren, Krister
    Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Moritz, Thomas
    Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Svensson, Michael
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Antti, Henrik
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    A Multivariate Screening Strategy for Investigating Metabolic Effects of Strenuous Physical Exercise in Human Serum2007In: Journal of Proteome Research, ISSN 1535-3893, Vol. 6, no 6, 2113-2120 p.Article in journal (Refereed)
    Abstract [en]

    A novel hypothesis-free multivariate screening methodology for the study of human exercise metabolism in blood serum is presented. Serum gas chromatography/time-of-flight mass spectrometry (GC/TOFMS) data was processed using hierarchical multivariate curve resolution (H-MCR), and orthogonal partial least-squares discriminant analysis (OPLS-DA) was used to model the systematic variation related to the acute effect of strenuous exercise. Potential metabolic biomarkers were identified using data base comparisons. Extensive validation was carried out including predictive H-MCR, 7-fold full cross-validation, and predictions for the OPLS-DA model, variable permutation for highlighting interesting metabolites, and pairwise t tests for examining the significance of metabolites. The concentration changes of potential biomarkers were verified in the raw GC/TOFMS data. In total, 420 potential metabolites were resolved in the serum samples. On the basis of the relative concentrations of the 420 resolved metabolites, a valid multivariate model for the difference between pre- and post-exercise subjects was obtained. A total of 34 metabolites were highlighted as potential biomarkers, all statistically significant (p < 8.1E-05). As an example, two potential markers were identified as glycerol and asparagine. The concentration changes for these two metabolites were also verified in the raw GC/TOFMS data.The strategy was shown to facilitate interpretation and validation of metabolic interactions in human serum as well as revealing the identity of potential markers for known or novel mechanisms of human exercise physiology. The multivariate way of addressing metabolism studies can help to increase the understanding of the integrative biology behind, as well as unravel new mechanistic explanations in relation to, exercise physiology.

  • 7. Cotgreave, Ian A
    et al.
    Goldschmidt, Lina
    Tonkonogi, Michail
    Svensson, Michael
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Differentiation-specific alterations to glutathione synthesis in and hormonally stimulated release from human skeletal muscle cells.2002In: The FASEB Journal, ISSN 0892-6638, E-ISSN 1530-6860, Vol. 16, no 3, 435-7 p.Article in journal (Refereed)
    Abstract [en]

    Muscle atrophy and cachexia are associated with many human diseases. These catabolic states are often associated with the loss of glutathione (GSH), which is thought to contribute to the induction of oxidative stress within the muscle. Glutathione synthesis and secretary characteristics were studied in human skeletal muscle myoblasts and myotube-like cells derived from the myoblasts by growth factor restriction. Differentiation was associated with a shift in the sulfur amino acid precursor specificity for synthesis of GSH from cystine to cysteine, as well as loss in ability to use extracellular glutathione and activation of methionine use. The thiol drug N-acetylcysteine was also shown to be an effective precursor irrespective of the state of differentiation. Additionally, myoblasts and myotube cultures were shown to secrete GSH continually, but only the differentiated cells responded to stress hormones such as glucagon, vasopressin, and phenylephrine, by increased secretion of the tripeptide. The data suggest that the skeletal muscle cells may provide an important hormonally regulated extra-hepatic source of systemic GSH and also shed light on the mechanisms of accelerated turnover of GSH operating during strenuous muscle activity and trauma. The data may also provide biochemical rationales for the nutritional and/or pharmacological manipulation of GSH with sulfur amino acid precursors during the treatment of muscle-specific oxidative stress and atrophy.

  • 8. Hellsten, Y
    et al.
    Svensson, M
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Sjödin, B
    Smith, S
    Christensen, A
    Richter, E A
    Bangsbo, J
    Allantoin formation and urate and glutathione exchange in human muscle during submaximal exercise.2001In: Free Radical Biology & Medicine, ISSN 0891-5849, E-ISSN 1873-4596, Vol. 31, no 11, 1313-22 p.Article in journal (Refereed)
    Abstract [en]

    Seven males performed two exhaustive cycling bouts (EX1 and EX2) at a work-rate of 90% of maximal oxygen uptake, separated by 60 min. During EX1 there was a significant accumulation of urate (from 0.16 +/- 0.02 to 0.27 +/- 0.03 micromol/kg d.w.) and allantoin (from 0.39 +/- 0.05 to 0.69 +/- 0.14 micromol/kg d.w.) in the muscle. An uptake of urate was observed in early recovery from EX1 (0-9 min: 486 +/- 136 micromol; p <.05). There was no exchange of total glutathione or cysteine over the muscle either during or after exercise, and muscle and plasma total glutathione remained unaltered (p <.05). The glycogen levels were lowered by 40% at the onset of EX2, yet the level of oxidative stress in EX1 and EX2 was similar as evidenced by a similar increase in muscle allantoin in both exercise bouts. The data suggest that urate is utilized as antioxidant in human skeletal muscle and that reactive oxygen species are formed in muscle during intense submaximal exercise. No net exchange of glutathione appears to occur over the muscle either at rest, during exercise or in recovery. Moreover, when an exhaustive exercise bout is repeated with lowered glycogen levels, the level of oxidative stress is not different than that of the first bout.

  • 9. Larsson, Anders
    et al.
    Svensson, Michael B
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Ronquist, Göran
    Åkerfeldt, Torbjörn
    Life style intervention in moderately overweight individuals is associated with decreased levels of cathepsins L and S in plasma2014In: Annals of Clinical and Laboratory Science, ISSN 0091-7370, E-ISSN 1550-8080, Vol. 44, no 3, 283-285 p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Adipose tissue cells produce cathepsins L and S, which have proatherogenic effects. Obesity is strongly linked to atherogenesis, cardiovascular morbidity, and mortality. OBJECTIVE: The aim of the present study was to see if life style interventions/weight reduction could decrease cathepsin L and S levels in blood plasma. METHOD: Study subjects (n=31) were recruited to a life style intervention program aiming at increased physical activity, more healthy eating habits, and weight reduction for most of the participants. Blood samples were collected at inclusion and after 4 and 8 weeks. RESULTS: Cathepsin L was significantly reduced at 4 weeks (p<0.0001) and 8 weeks (p=0.0004). A similar reduction was also seen for cathepsin S at 4 weeks (p=0.03) and 8 weeks (p=0.008). No significant change in fractalkine values was observed at 4 weeks (p=0.58), but a significant increase was apparent at 8 weeks (p=0.0002). CONCLUSION: The intervention program resulted in significant reductions of cathepsin L and S levels in plasma after 4 and 8 weeks of intervention.

  • 10. Malm, C
    et al.
    Svensson, M
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Ekblom, B
    Sjödin, B
    Effects of ubiquinone-10 supplementation and high intensity training on physical performance in humans.1997In: Acta Physiologica Scandinavica, ISSN 0001-6772, E-ISSN 1365-201X, Vol. 161, no 3, 379-84 p.Article in journal (Refereed)
    Abstract [en]

    This study investigated the effects of oral supplementation with ubiquinone-10 (Q10) (n = 9) compared with a placebo (n = 9) on aerobic and anaerobic physical performance over 22 days of supplementation. The supplementation period included 5 days of high intensity anaerobic training between days 11 and 14. The results demonstrated, that on an anaerobic (10 x 10 s) cycling test, the placebo group showed a significantly greater improvement than the Q10-group after a supplementation and training period (P < 0.001). Further, the Q10 group had a significantly lower increase in total work performed during the seven training sessions (15 x 10 s) compared with the placebo group (P < 0.001). There was a significant increase in maximal blood lactate accumulation during cycling in the both groups, when compared with levels before the training and recovery period. There was no significant difference between the groups, either in VO2max determined during running, or in submaximal and peak VO2, Rate of Perceived Exertion, respiratory quotient, blood lactate concentration or heart rate determined during submaximal and maximal cycling. Although insignificant (P = 0.1-0.3), there was evidence of higher submaximal VO2 (55-80% of VO2peak) during cycling in the Q10-group compared with the placebo group after training and recovery. It is concluded that with high intensity anaerobic training, there was a significantly greater increase in anaerobic performance in the placebo group compared with the Q10 group. The results suggest less increase in physical performance with Q10 supplement and high intensity anaerobic training, compared with placebo.

  • 11. Malm, C
    et al.
    Svensson, M
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Sjöberg, B
    Ekblom, B
    Sjödin, B
    Supplementation with ubiquinone-10 causes cellular damage during intense exercise.1996In: Acta Physiologica Scandinavica, ISSN 0001-6772, E-ISSN 1365-201X, Vol. 157, no 4, 511-2 p.Article in journal (Refereed)
  • 12.
    Malm, Christer
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Hadrevi, Jenny
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Bergström, Sven-Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Pedrosa-Domellof, Fatima
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Antti, Henrik
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Svensson, Michael
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Frängsmyr, Lars
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Evaluation of 2-D DIGE for skeletal muscle: Protocol and repeatability2008In: The Scandinavian Journal of Clinical & Laboratory Investigation, Vol. 68, no 8, 793-800 p.Article in journal (Refereed)
    Abstract [en]

    Proteomic analysis has the potential to yield vast amounts of data. The available proteomic methods have been hampered by methodological errors in quantification due to large gel-to-gel variations. The inclusion of an internal standard greatly reduces this variation, and therefore the purpose of this investigation was: 1) to develop a sample preparation protocol for human skeletal muscle for two-dimensional differentiated gel electrophoresis (DIGE) and 2) to investigate the repeatability of one particular system, the Ettan™ DIGE. To test repeatability, nine aliquots from the same homogenate were labelled with three different CyDye™ dyes (Cy2, Cy3, Cy5). Samples were run on 1824 cm gels, scanned with a Typhoon™ 9410 laser scanner and analysed in the DeCyder™ software. When selecting spots appearing only in triplicate (n = 1314), the mean error was 1.7 % (SD: 10.5 %; 95 % CI: 1.1-2.4 %). When setting the significance level to 99 %, no false-positive changes in protein volume ratios were detected. In the protocol presented here, only 0.5 mg tissue was used and separation of >2500 distinct protein spots in the pH range 3-11 and MW 10-200 kDa. Changes in protein abundance of <20 % could be detected. The method is especially useful when comparing muscle proteins between different conditions; for example, healthy and diseased tissue, before and after treatment or different exercise protocols.

  • 13. Sahlin, Kent
    et al.
    Fernström, Maria
    Svensson, Michael
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Tonkonogi, Michail
    No evidence of an intracellular lactate shuttle in rat skeletal muscle.2002In: Journal of Physiology, ISSN 0022-3751, E-ISSN 1469-7793, Vol. 541, no Pt 2, 569-74 p.Article in journal (Refereed)
    Abstract [en]

    The concerted view is that cytosolic pyruvate is transferred into mitochondria and after oxidative decarboxylation further metabolized in the tricarboxylic acid cycle. Recently this view has been challenged. Based on experimental evidence from rat skeletal muscle it has been concluded that mitochondria predominantly oxidize lactate in vivo and that this constitutes part of an 'intracellular lactate shuttle'. This view appears to be gaining acceptance in the scientific community and due to its conceptual importance, confirmation by independent experiments is required. We have repeated the experiments in mitochondria isolated from rat soleus muscle. Contrary to the previously published findings we cannot find any mitochondrial respiration with lactate. Analysis of lactate dehydrogenase (LDH) by spectrophotometry demonstrated that the activity in the mitochondrial fraction was only 0.7 % of total activity. However, even when external LDH was added to mitochondria, there were no signs of respiration with lactate. In the presence of conditions where lactate is converted to pyruvate (external additions of both LDH and NAD(+)), mitochondrial oxygen consumption increased. Furthermore, we provide theoretical evidence that direct mitochondrial lactate oxidation is energetically unlikely. Based on the present data we conclude that direct mitochondrial lactate oxidation does not occur in skeletal muscle. The presence of an 'intracellular lactate shuttle' can therefore be questioned.

  • 14.
    Svensson, M B
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Ekblom, B
    Cotgreave, I A
    Norman, B
    Sjöberg, B
    Ekblom, O
    Sjödin, B
    Sjödin, A
    Adaptive stress response of glutathione and uric acid metabolism in man following controlled exercise and diet.2002In: Acta Physiologica Scandinavica, ISSN 0001-6772, E-ISSN 1365-201X, Vol. 176, no 1, 43-56 p.Article in journal (Refereed)
    Abstract [en]

    Ergometer cycling performance as well as acute exercise-induced changes in the metabolism of energy-intermediates and glutathione (GSH) were investigated in skeletal muscle (SM) of 15 healthy young male subjects (VO(2max) approximately 54.7 mL kg(-1) min(-1), age approximately 25 years), before and after 3 days of controlled 'ìoverload-training' in combination with either high (62% of energy intake) or low (26% of energy intake) dietary intake of carbohydrates. The intake of a carbohydrate-rich diet clearly reduced the depletion of SM glycogen following the short-term training period, paralleled with a positive effect on the endurance performance, but not on high-intensity work-performance. An 'delayed over-reaching effect', defined as impaired work-performance, was observed after 2.5 days of recovery from the short-term training period, irrespective of the carbohydrate content of the diet and basal glycogen level in SM. Taken together, the main and novel findings of present investigation are: (1) an acute decrease of reduced GSH content and altered thiol-redox homeostasis in SM induced by strenuous high-intensity exercise; (2) an adaptive elevation of basal GSH level following the short-term training period; (3) an adaptive decrease of basal GSH level following 2.5 days recovery from training; (4) evidence of a relationship between the SM fibre type, physical performance capacity and GSH turnover during acute bouts of exercise; and (5) no evident effect of the level of carbohydrate intake on metabolism of GSH or energy intermediates. Furthermore, the induction of acute oxidative stress in exercising human SM and the adaptive responses to training are suggested to provide a protective antioxidant phenotype to the exercising SM during periods with repeated intense intermittent training.

  • 15.
    Svensson, M
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Malm, C
    Tonkonogi, M
    Ekblom, B
    Sjödin, B
    Sahlin, K
    Effect of Q10 supplementation on tissue Q10 levels and adenine nucleotide catabolism during high-intensity exercise.1999In: International Journal of Sport Nutrition, ISSN 1050-1606, Vol. 9, no 2, 166-80 p.Article in journal (Refereed)
    Abstract [en]

    The aim of the present study was to investigate the concentration of ubiquinone-10 (Q10), at rest, in human skeletal muscle and blood plasma before and after a period of high-intensity training with or without Q10 supplementation. Another aim was to explore whether adenine nucleotide catabolism, lipid peroxidation, and mitochondrial function were affected by Q10 treatment. Seventeen young healthy men were assigned to either a control (placebo) or Q10-supplementation (120 mg/day) group. Q10 supplementation resulted in a significantly higher plasma Q10/total cholesterol level on Days 11 and 20 compared with Day 1. There was no significant change in the concentration of Q10 in skeletal muscle or in isolated skeletal muscle mitochondria in either group. Plasma hypoxanthine and uric acid concentrations increased markedly after each exercise test session in both groups. After the training period, the postexercise increase in plasma hypoxanthine was markedly reduced in both groups, but the response was partially reversed after the recovery period. It was concluded that Q10 supplementation increases the concentration of Q10 in plasma but not in skeletal muscle.

  • 16.
    Thysell, Elin
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Chorell, Elin
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Svensson, Michael B
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Jonsson, Pär
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Antti, Henrik
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Validated and Predictive Processing of Gas Chromatography-Mass Spectrometry Based Metabolomics Data for Large Scale Screening Studies, Diagnostics and Metabolite Pattern Verification2012In: Metabolites, ISSN 2218-1989, Vol. 2, 796-817 p.Article in journal (Refereed)
    Abstract [en]

    The suggested approach makes it feasible to screen large metabolomics data, sample sets with retained data quality or to retrieve significant metabolic information from small sample sets that can be verified over multiple studies. Hierarchical multivariate curve resolution (H-MCR), followed by orthogonal partial least squares discriminant analysis (OPLS-DA) was used for processing and classification of gas chromatography/time of flight mass spectrometry (GC/TOFMS) data characterizing human serum samples collected in a study of strenuous physical exercise. The efficiency of predictive H-MCR processing of representative sample subsets, selected by chemometric approaches, for generating high quality data was proven. Extensive model validation by means of cross-validation and external predictions verified the robustness of the extracted metabolite patterns in the data. Comparisons of extracted metabolite patterns between models emphasized the reliability of the methodology in a biological information context. Furthermore, the high predictive power in longitudinal data provided proof for the potential use in clinical diagnosis. Finally, the predictive metabolite pattern was interpreted physiologically, highlighting the biological relevance of the diagnostic pattern. The suggested approach makes it feasible to screen large metabolomics data, sample sets with retained data quality or to retrieve significant metabolic information from small sample sets that can be verified over multiple studies. Hierarchical multivariate curve resolution (H-MCR), followed by orthogonal partial least squares discriminant analysis (OPLS-DA) was used for processing and classification of gas chromatography/time of flight mass spectrometry (GC/TOFMS) data characterizing human serum samples collected in a study of strenuous physical exercise. The efficiency of predictive H-MCR processing of representative sample subsets, selected by chemometric approaches, for generating high quality data was proven. Extensive model validation by means of cross-validation and external predictions verified the robustness of the extracted metabolite patterns in the data. Comparisons of extracted metabolite patterns between models emphasized the reliability of the methodology in a biological information context. Furthermore, the high predictive power in longitudinal data provided proof for the potential use in clinical diagnosis. Finally, the predictive metabolite pattern was interpreted physiologically, highlighting the biological relevance of the diagnostic pattern.

  • 17.
    Thysell, Elin
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Chorell, Elin
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Svensson, Michael B.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Moritz, Thomas
    Jonsson, Pär
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Antti, Henrik
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Processing of mass spectrometry based metabolomics data for large scale screening studies and diagnosticsManuscript (preprint) (Other academic)
    Abstract [en]

    In mass spectrometry based metabolomics predictive data processing and sample classification based on representative sample subsets makes it possible to screen large sample banks or data sets in an efficient fashion regarding both data quality and processing time. This is a requirement for making use of high sensitivity and complexity metabolite data and to turn the metabolomics field into a competitive omics platform for biological interpretation and diagnostics. Predictive metabolomics by means of hierarchical multivariate curve resolution (H-MCR) followed by orthogonal partial least squares discriminant analysis (OPLS-DA) was used for the processing and classification of gas chromatography/time of flight mass spectrometry (GC/TOFMS) data characterizing human blood serum samples collected in a study of strenuous physical exercise. The efficiency of the predictive processing as a high throughput tool for generating high quality data is clearly proven and stated as a main benefit of the method. Extensive model validation schemes by means of cross validation and external predictions verified the robustness of the extracted systematic patterns in the data. Comparisons regarding the extracted metabolite patterns between models emphasized the reliability of the methodology in a biological information context. Furthermore, the high predictive power concerning longitudinal predictions provided proof for the diagnostic potential of the methodology. Finally, the predictive metabolite pattern was interpreted physiologically as well as verified in the literature, highlighting the biological relevance of the diagnostic pattern. The suggested approach makes it feasible to screen large data or sample sets with retained data quality and interpretation and to do this in a high throughput fashion. The method could be of value for sample bank mining, metabolome-wide association studies, verification of marker patterns and development of diagnostic systems.

  • 18.
    Thysell, Elin
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Chorell, Elin
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Svensson, Michael
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Jonsson, Pär
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Antti, Henrik
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Validated and predictive processing of gas chromatography-mass spectra screening studies, diagnostics and metabolite pattern verification2012In: Metabolites, ISSN 2218-1989, E-ISSN 2218-1989, Vol. 2, no 4, 796-817 p.Article in journal (Refereed)
    Abstract [en]

    The suggested approach makes it feasible to screen large metabolomics data, sample sets with retained data quality or to retrieve significant metabolic information from small sample sets that can be verified over multiple studies. Hierarchical multivariate curve resolution (H-MCR), followed by orthogonal partial least squares discriminant analysis (OPLS-DA) was used for processing and classification of gas chromatography/time of flight mass spectrometry (GC/TOFMS) data characterizing human serum samples collected in a study of strenuous physical exercise. The efficiency of predictive H-MCR processing of representative sample subsets, selected by chemometric approaches, for generating high quality data was proven. Extensive model validation by means of cross-validation and external predictions verified the robustness of the extracted metabolite patterns in the data. Comparisons of extracted metabolite patterns between models emphasized the reliability of the methodology in a biological information context. Furthermore, the high predictive power in longitudinal data provided proof for the potential use in clinical diagnosis. Finally, the predictive metabolite pattern was interpreted physiologically, highlighting the biological relevance of the diagnostic pattern.

  • 19. Tonkonogi, M
    et al.
    Walsh, B
    Svensson, M
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Sahlin, K
    Mitochondrial function and antioxidative defence in human muscle: effects of endurance training and oxidative stress.2000In: Journal of Physiology, ISSN 0022-3751, E-ISSN 1469-7793, Vol. 528 Pt 2, 379-88 p.Article in journal (Refereed)
    Abstract [en]

    The influence of endurance training on oxidative phosphorylation and the susceptibility of mitochondrial oxidative function to reactive oxygen species (ROS) was investigated in skeletal muscle of four men and four women. Mitochondria were isolated from muscle biopsies taken before and after 6 weeks of endurance training. Mitochondrial respiration was measured before and after exposure of mitochondria to exogenous ROS (H2O2 + FeCl2). Endurance training increased peak pulmonary O2 uptake (VO2,peak) by 24 % and maximal ADP-stimulated mitochondrial oxygen consumption (state 3) by 40% (P<0.05). Respiration in the absence of ADP (state 4), the respiratory control ratio (RCR = state 3/state 4) and the ratio between added ADP and consumed oxygen (P/O) remained unchanged by the training programme. Exposure to ROS reduced state 3 respiration but the effect was not significantly different between pre- and post-training samples. State 4 oxygen consumption increased after exposure to ROS both before (+189 %, P< 0.05) and after training (+243 %, P<0.05) and the effect was significantly higher after training (P<0.05, pre- vs. post-training). The augmented state 4 respiration could in part be attenuated by atractyloside, which indicates that ADP/ATP translocase was affected by ROS. The P/O ratio in ROS-treated mitochondria was significantly lower (P<0.05) compared to control conditions, both before (-18.6+/-2.2 %) and after training (-18.5+/-1.1%). Muscle activities of superoxide dismutase (mitochondrial and cytosolic), glutathione peroxidase and muscle glutathione status were unaffected by training. There was a positive correlation between muscle superoxide dismutase activity and age (r = 0.75; P<0.05; range of age 20-37 years), which may reflect an adaptation to increased generation of ROS in senescent muscle. The muscle glutathione pool was more reduced in subjects with high activity of glutathione peroxidase (r = 0.81; P<0.05). The influence of short-term training on mitochondrial oxygen consumption has for the first time been investigated in human skeletal muscle. The results showed that maximal mitochondrial oxidative power is increased after endurance training but that the efficiency of energy transfer (P/O ratio) remained unchanged. Antioxidative defence was unchanged after training when expressed relative to muscle weight. Although this corresponds to a reduced antioxidant protection per individual mitochondrion, the sensitivity of aerobic energy transfer to ROS was unchanged. However, the augmented ROS-induced non-coupled respiration after training indicates an increased susceptibility of mitochondrial membrane proton conductance to oxidative stress.

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