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  • 1. Bigard, X.
    et al.
    Chaillou, Thomas
    Université Grenoble Alpes, Saint-Martin-d'Heres, France .
    Sanchez, H.
    Malgoyre, A.
    Koulmann, N,
    How to build high oxidative skeletal muscle?: Interaction between energy stress and muscle growth2010Conference paper (Refereed)
  • 2.
    Chaillou, Thomas
    Örebro University, School of Health Sciences.
    Impaired ribosome biogenesis could contribute to anabolic resistance to strength exercise in the elderly2017In: Journal of Physiology, ISSN 0022-3751, E-ISSN 1469-7793, Vol. 595, no 5, p. 1447-1448Article, review/survey (Refereed)
  • 3.
    Chaillou, Thomas
    Örebro University, School of Health Sciences.
    Ribosome specialization and its potential role in the control of protein translation and skeletal muscle size2019In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 127, no 2, p. 599-607Article, review/survey (Refereed)
    Abstract [en]

    The ribosome is typically viewed as a supramolecular complex with constitutive and invariant capacity in mediating translation of mRNA into protein. This view has been challenged by recent research revealing that ribosome composition could be heterogeneous, and this heterogeneity leads to functional ribosome specialization. This review presents the idea that ribosome heterogeneity results from changes in its various components, including variations in ribosomal protein (RP) composition, post-translational modifications of RPs, changes in ribosomal-associated proteins, alternative forms of rRNA and post-transcriptional modifications of rRNAs. Ribosome heterogeneity could be orchestrated at several levels and may depend on numerous factors, such as the subcellular location, cell type and tissue specificity, the development state, cell state, ribosome biogenesis, RP turnover, physiological stimuli and circadian rhythm. Ribosome specialization represents a completely new concept for the regulation of gene expression. Specialized ribosomes could modulate several aspects of translational control, such as mRNA translation selectivity, translation initiation, translational fidelity and translation elongation. Recent research indicates that the expression of Rpl3 is markedly increased, while that of Rpl3l is highly reduced during mouse skeletal muscle hypertrophy. Moreover, Rpl3l overexpression impairs the growth and myogenic fusion of myotubes. Although the function of Rpl3 and Rpl3l in the ribosome remains to be clarified, these findings suggest that ribosome specialization may be potentially involved in the control of protein translation and skeletal muscle size. Limited data concerning ribosome specialization are currently available in skeletal muscle. Future investigations have the potential to delineate the function of specialized ribosomes in skeletal muscle.

  • 4.
    Chaillou, Thomas
    Örebro University, School of Health Sciences.
    Skeletal Muscle Fiber Type in Hypoxia: Adaptation to High-Altitude Exposure and Under Conditions of Pathological Hypoxia2018In: Frontiers in Physiology, E-ISSN 1664-042X, Vol. 9, article id 1450Article, review/survey (Refereed)
    Abstract [en]

    Skeletal muscle is able to modify its size, and its metabolic/contractile properties in response to a variety of stimuli, such as mechanical stress, neuronal activity, metabolic and hormonal influences, and environmental factors. A reduced oxygen availability, called hypoxia, has been proposed to inducemetabolic adaptations and loss ofmass in skeletal muscle. In addition, several evidences indicate that muscle fiber-type composition could be affected by hypoxia. The main purpose of this review is to explore the adaptation of skeletal muscle fiber-type composition to exposure to high altitude (ambient hypoxia) and under conditions of pathological hypoxia, including chronic obstructive pulmonary disease (COPD), chronic heart failure (CHF) and obstructive sleep apnea syndrome (OSAS). The muscle fiber-type composition of both adult animals and humans is not markedly altered during chronic exposure to high altitude. However, the fast-to-slow fiber-type transition observed in hind limb muscles during post-natal development is impaired in growing rats exposed to severe altitude. A slow-to-fast transition in fiber type is commonly found in lower limb muscles from patients with COPD and CHF, whereas a transition toward a slower fiber-type profile is often found in the diaphragm muscle in these two pathologies. A slow-to-fast transformation in fiber type is generally observed in the upper airway muscles in rodent models of OSAS. The factors potentially responsible for the adaptation of fiber type under these hypoxic conditions are also discussed in this review. The impaired locomotor activity most likely explains the changes in fiber type composition in growing rats exposed to severe altitude. Furthermore, chronic inactivity and muscle deconditioning could result in the slow-to-fast fiber-type conversion in lower limb muscles during COPD and CHF, while the factors responsible for the adaptation of muscle fiber type during OSAS remain hypothetical. Finally, the role played by cellular hypoxia, hypoxia-inducible factor-1 alpha (HIF-1 alpha), and other molecular regulators in the adaptation of muscle fiber-type composition is described in response to high altitude exposure and conditions of pathological hypoxia.

  • 5.
    Chaillou, Thomas
    et al.
    Örebro University, School of Health Sciences.
    Cheng, Arthur
    Karolinska Institutet, Stockholm, Sweden.
    A dose of 5,000 km.h of severe hypoxia (at > 5,000 m altitude) is probably required to induce skeletal muscle wasting in humans2017In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 122, no 2, p. 410-410Article in journal (Refereed)
  • 6.
    Chaillou, Thomas
    et al.
    Örebro University, School of Health Sciences.
    Cheng, Arthur J.
    Faculty of Health, School of Kinesiology and Health Sciences, York University, Canada.
    Mechanisms of prolonged low-frequency force depression: in-vivo studies get us closer to the truth2019In: American Journal of Physiology. Regulatory Integrative and Comparative Physiology, ISSN 0363-6119, E-ISSN 1522-1490, Vol. 316, no 5, p. R502-R503Article in journal (Refereed)
  • 7.
    Chaillou, Thomas
    et al.
    Karolinska Institute, Stockholm, Sweden.
    Hynynen, H.
    University of Eastern Finland, Joensuu, Finland.
    Ferreira, D.
    Karolinska Institute, Stockholm, Sweden.
    Pironti, G.
    Karolinska Institute, Stockholm, Sweden.
    Andersson, D.C.
    Karolinska Institute, Stockholm, Sweden.
    Ruas, J.
    Karolinska Institute, Stockholm, Sweden.
    Tavi, P.
    University of Eastern Finland, Joensuu, Finland.
    Lanner, J.T.
    Karolinska Institute, Stockholm, Sweden.
    The mitochondrial NDUFA4L2 protein: a novel modulator of skeletal muscle mass and force2016Conference paper (Refereed)
  • 8.
    Chaillou, Thomas
    et al.
    Karolinska Institutet, Stockholm, Sweden.
    Hynynen, H
    University of Eastern Finland, Joensuu, Finland.
    Ferreira, D
    Karolinska Institutet, Stockholm, Sweden.
    Pironti, G
    Karolinska Institutet, Stockholm, Sweden.
    Kenne, E
    Karolinska Institutet, Stockholm, Sweden.
    Andersson, D C
    Karolinska Institutet, Stockholm, Sweden; Karolinska University Hospital, Stockholm, Sweden.
    Ruas, J L
    Karolinska Institutet, Stockholm, Sweden.
    Tavi, P
    University of Eastern Finland, Joensuu, Finland.
    Lanner, J T
    Karolinska Institutet, Stockholm, Sweden.
    NDUFA4L2: Connecting metabolic signals and mitochondrial function in cardiac and skeletal muscle2016In: Free Radical Biology & Medicine, ISSN 0891-5849, E-ISSN 1873-4596, Vol. 100, no Suppl., p. S186-S186Article in journal (Refereed)
    Abstract [en]

    The nuclear-encoded mitochondrial protein NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 4-like 2 (NDUFA4L2) was recently identified. NDUFAe4L2 is shown to be induced by hypoxia via HIF1α and is thought to inhibit production of mitochondrial reactive oxygen species in fibroblasts exposed to hypoxia. Here the aim was to characterize the role of NDUFA4L2 in the mitochondria-rich tissues skeletal and cardiac muscle. We show hypoxia induced NDUFA4L2 expression in isolated muscle fibers and in cardiomyocytes with full activation after ~3-6 h in hypoxia. The half-maximal O2 level for NDUFA4L2 expression (~4.6 % of ambient O2) suggests sensitivity to changes in O2 tension that occur under physiological conditions (e.g. exercise, moderate ischemia). We identified that the NDUFA4L2 gene promoter has binding sites for transcription factors other than HIF-1α; repetitive sites for PPARα,γ and one for Nrf2. NDUFA4L2 overexpression resulted in functional effects on skeletal and cardiac muscle; e.g. it alters cellular Ca2+ signaling and the expression of Ca2+ handling genes. Further, NDUFA4L2 overexpression reduces muscle mass (~20%), leading to a decreased force production in skeletal muscle. The NDUFA4L2-induced loss of muscle mass was associated with increases in mRNA levels of e.g. MurF1, Mul1, caspase-3 and Bax. Additionally, femoral artery ligation (FAL) induced NDUFA4L2 expression, which correlates with the decreased force production eight days post-FAL in skeletal muscle. Moreover, NDUFA4L2 upregulates antioxidant gene expression and silencing NDUFA4L2 makes cardiac cells less tolerant to hypoxia/re-oxygenation. Our results suggest that NDUFA4L2 expression affects vital functions in muscle cells and at least part of this effect is mediated by a link between NDUFA4L2 and nuclear gene expression. Thus, NDUFA4L2 might act as an integrator of the nutritional, environmental and functional status in muscle cells.

  • 9.
    Chaillou, Thomas
    et al.
    Karolinska Institute, Stockholm, Sweden.
    Ivarsson, N
    Mijwel, S
    Cheng, A
    Rundqvist, H
    Lanner, J
    Breast-cancer-induced muscle weakness: benefits of physical exercise to restore muscle function2015Conference paper (Refereed)
  • 10.
    Chaillou, Thomas
    et al.
    Center for Muscle Biology, University of Kentucky, Lexington, Kentucky, USA; Department of Physiology, College of Medicine, University of Kentucky, Lexington, Kentucky, USA.
    Jackson, J.R.
    Center for Muscle Biology, University of Kentucky, Lexington, Kentucky, USA; Department of Physiology, College of Medicine, University of Kentucky, Lexington, Kentucky, USA; Department of Rehabilitation Sciences, College of Health Sciences, University of Kentucky, Lexington, Kentucky, USA.
    England, J.H.
    Center for Muscle Biology, University of Kentucky, Lexington, Kentucky, USA; Department of Physiology, College of Medicine, University of Kentucky, Lexington, Kentucky, USA.
    Kirby, T.J.
    Center for Muscle Biology, University of Kentucky, Lexington, Kentucky, USA; Department of Physiology, College of Medicine, University of Kentucky, Lexington, Kentucky, USA; Department of Rehabilitation Sciences, College of Health Sciences, University of Kentucky, Lexington, Kentucky, USA.
    Richards-White, J.
    Department of Rehabilitation Sciences, College of Health Sciences, University of Kentucky, Lexington, Kentucky, USA.
    Esser, K.A.
    Center for Muscle Biology, University of Kentucky, Lexington, Kentucky, USA; Department of Physiology, College of Medicine, University of Kentucky, Lexington, Kentucky, USA.
    Dupont-Versteegden, E.E.
    Center for Muscle Biology, University of Kentucky, Lexington, Kentucky, USA; Department of Physiology, College of Medicine, University of Kentucky, Lexington, Kentucky, USA; Department of Rehabilitation Sciences, College of Health Sciences, University of Kentucky, Lexington, Kentucky, USA.
    McCarthy, J.J.
    Center for Muscle Biology, University of Kentucky, Lexington, Kentucky, USA; Department of Physiology, College of Medicine, University of Kentucky, Lexington, Kentucky, USA.
    Identification of a conserved set of upregulated genes in mouse skeletal muscle hypertrophy and regrowth2015In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 118, p. 86-97Article in journal (Refereed)
    Abstract [en]

    The purpose of this study was to compare the gene expression profile of mouse skeletal muscle undergoing two forms of growth (hypertrophy and regrowth) with the goal of identifying a conserved set of differentially expressed genes. Expression profiling by microarray was performed on the plantaris muscle subjected to 1, 3, 5, 7, 10, and 14 days of hypertrophy or regrowth following 2 wk of hind-limb suspension. We identified 97 differentially expressed genes (≥2-fold increase or ≥50% decrease compared with control muscle) that were conserved during the two forms of muscle growth. The vast majority (∼90%) of the differentially expressed genes was upregulated and occurred at a single time point (64 out of 86 genes), which most often was on the first day of the time course. Microarray analysis from the conserved upregulated genes showed a set of genes related to contractile apparatus and stress response at day 1, including three genes involved in mechanotransduction and four genes encoding heat shock proteins. Our analysis further identified three cell cycle-related genes at day and several genes associated with extracellular matrix (ECM) at both days 3 and 10. In conclusion, we have identified a core set of genes commonly upregulated in two forms of muscle growth that could play a role in the maintenance of sarcomere stability, ECM remodeling, cell proliferation, fast-to-slow fiber type transition, and the regulation of skeletal muscle growth. These findings suggest conserved regulatory mechanisms involved in the adaptation of skeletal muscle to increased mechanical loading.

  • 11. Chaillou, Thomas
    et al.
    Koulmann, N.
    Beaudry, M.
    Bigard, X.
    Molecular mechanisms involved in the muscle mass control2011Conference paper (Refereed)
  • 12.
    Chaillou, Thomas
    et al.
    Département Environnements Opérationnels, Institut de Recherche Biomédicale des Armées Antenne de la Tronche, La Tronche cedex, France.
    Koulmann, N.
    Département Environnements Opérationnels, Institut de Recherche Biomédicale des Armées Antenne de la Tronche, La Tronche cedex, France; Ecole du Val-de-Grâce, Paris, France.
    Meunier, A.
    Département Environnements Opérationnels, Institut de Recherche Biomédicale des Armées Antenne de la Tronche, La Tronche cedex, France.
    Chapot, R.
    Département Environnements Opérationnels, Institut de Recherche Biomédicale des Armées Antenne de la Tronche, La Tronche cedex, France.
    Serrurier, B.
    Département Environnements Opérationnels, Institut de Recherche Biomédicale des Armées Antenne de la Tronche, La Tronche cedex, France.
    Beaudry, M.
    Laboratoire Réponses Cellulaires et Fonctionnelles À l'Hypoxie, EA2363, Sorbonne-Paris-Cité, Université Paris, Bobigny Cedex, France.
    Bigard, X.
    Département Environnements Opérationnels, Institut de Recherche Biomédicale des Armées Antenne de la Tronche, La Tronche cedex, France.
    Effect of hypoxia exposure on the recovery of skeletal muscle phenotype during regeneration2014In: Molecular and Cellular Biochemistry, ISSN 0300-8177, E-ISSN 1573-4919, Vol. 390, no 1-2, p. 31-40Article in journal (Refereed)
    Abstract [en]

    Hypoxia impairs the muscle fibre-type shift from fast-to-slow during post-natal development; however, this adaptation could be a consequence of the reduced voluntary physical activity associated with hypoxia exposure rather than the result of hypoxia per se. Moreover, muscle oxidative capacity could be reduced in hypoxia, particularly when hypoxia is combined with additional stress. Here, we used a model of muscle regeneration to mimic the fast-to-slow fibre-type conversion observed during post-natal development. We hypothesised that hypoxia would impair the recovery of the myosin heavy chain (MHC) profile and oxidative capacity during muscle regeneration. To test this hypothesis, the soleus muscle of female rats was injured by notexin and allowed to recover for 3, 7, 14 and 28 days under normoxia or hypobaric hypoxia (5,500 m altitude) conditions. Ambient hypoxia did not impair the recovery of the slow MHC profile during muscle regeneration. However, hypoxia moderately decreased the oxidative capacity (assessed from the activity of citrate synthase) of intact muscle and delayed its recovery in regenerated muscle. Hypoxia transiently increased in both regenerated and intact muscles the content of phosphorylated AMPK and Pgc-1α mRNA, two regulators involved in mitochondrial biogenesis, while it transiently increased in intact muscle the mRNA level of the mitophagic factor BNIP3. In conclusion, hypoxia does not act to impair the fast-to-slow MHC isoform transition during regeneration. Hypoxia alters the oxidative capacity of intact muscle and delays its recovery in regenerated muscle; however, this adaptation to hypoxia was independent of the studied regulators of mitochondrial turn-over.

  • 13.
    Chaillou, Thomas
    et al.
    Département Environnements opérationnels, Institut de Recherche Biomédicale des Armées Antenne de la Tronche, La Tronche, France.
    Koulmann, N.
    Département Environnements opérationnels, Institut de Recherche Biomédicale des Armées Antenne de la Tronche, La Tronche, France; Ecole du Val-de-Grâce, Paris, France.
    Meunier, A.
    Département Environnements opérationnels, Institut de Recherche Biomédicale des Armées Antenne de la Tronche, La Tronche, France.
    Malgoyre, A.
    Département Environnements opérationnels, Institut de Recherche Biomédicale des Armées Antenne de la Tronche, La Tronche, France.
    Serrurier, B.
    Département Environnements opérationnels, Institut de Recherche Biomédicale des Armées Antenne de la Tronche, La Tronche, France.
    Beaudry, M.
    Laboratoire Réponses cellulaires et fonctionnelles à l'hypoxie, Université Paris, Sorbonne-Paris-Cité, France.
    Bigard, X.
    Département Environnements opérationnels, Institut de Recherche Biomédicale des Armées Antenne de la Tronche, La Tronche, France; Ecole du Val-de-Grâce, Paris, France.
    Effect of hypoxia exposure on the phenotypic adaptation in remodelling skeletal muscle submitted to functional overload2013In: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 209, no 4, p. 272-282Article in journal (Refereed)
    Abstract [en]

    Aim: To determine whether hypoxia influences the phenotypic adaptation of skeletal muscle induced by mechanical overload.

    Methods: Plantaris muscles of female rats were submitted to mechanical overload following synergist ablation. After 3 days of overload, rats were exposed to either hypobaric hypoxia (equivalent to 5500 m) or normoxia. Muscles were collected after 5, 12 and 56 days of overload (i.e. after 3, 9 and 53 days of hypoxia). We determined the myosin heavy chain (MHC) distribution, mRNA levels of myocyte-enriched calcineurin-integrating protein 1 (MCIP1) to indirectly assess calcineurin activity, the changes in oxidative capacity from the activities of citrate synthase (CS) and cytochrome c oxidase (COX), and the expression of regulators involved in mitochondrial biogenesis (Pgc-1α, NRF1 and Tfam) and degradation (BNIP-3).

    Results: Hypoxia did not alter the fast-to-slow MHC shift and the increase in calcineurin activity induced by overload; it only transiently slowed down the overload-induced transition in MHC isoforms. Hypoxia similarly decreased CS and COX activities in overloaded and control muscles. Nuclear respiratory factor 1 (NRF1) and transcription factor A (Tfam) mRNA and BNIP-3 protein were not influenced by hypoxia in overloaded muscles, whereas Pgc-1α mRNA and protein contents did not correlate with changes in oxidative capacity.

    Conclusion: Hypoxia is not a critical stimulus to modulate the fast-to-slow MHC transition associated with overload. Thus, the impairment of the fast-to-slow fibre shift often observed during post-natal development in hypoxia could be explained by the lower voluntary locomotor activity associated with hypoxia. Hypoxia alters mitochondrial oxidative capacity, but this adaptive response is similar in overloaded and control muscles.

  • 14.
    Chaillou, Thomas
    et al.
    Département Environnements Opérationnels, Institut de Recherche Biomédicale des Armées, Antenne de la Tronche, La Tronche, France; Center for Muscle Biology, Department of Physiology, University of Kentucky, Lexington KY, United States.
    Koulmann, N.
    Département Environnements Opérationnels, Institut de Recherche Biomédicale des Armées, Antenne de la Tronche, La Tronche, France; Ecole du Val-de-Grâce, Paris, France.
    Meunier, A.
    Département Environnements Opérationnels, Institut de Recherche Biomédicale des Armées, Antenne de la Tronche, La Tronche, France.
    Pugnière, P.
    Pôle Génomique, Institut de Recherche Biomédicale des Armées, La Tronche, France.
    McCarthy, J.J.
    Center for Muscle Biology, Department of Physiology, University of Kentucky, Lexington KY, United States.
    Beaudry, M.
    Laboratoire Réponses Cellulaires et Fonctionnelles À l'Hypoxie, Sorbonne-Paris-Cité, Université Paris13, Paris, France.
    Bigard, X.
    Département Environnements Opérationnels, Institut de Recherche Biomédicale des Armées, Antenne de la Tronche, La Tronche, France; Ecole du Val-de-Grâce, Paris, France.
    Ambient hypoxia enhances the loss of muscle mass after extensive injury2014In: Pflügers Archiv: European Journal of Physiology, ISSN 0031-6768, E-ISSN 1432-2013, Vol. 466, no 3, p. 587-598Article in journal (Refereed)
    Abstract [en]

    Hypoxia induces a loss of skeletal muscle mass and alters myogenesis in vitro, but whether it affects muscle regeneration in vivo following injury remains to be elucidated. We hypothesized that hypoxia would impair the recovery of muscle mass during regeneration. To test this hypothesis, the soleus muscle of female rats was injured by notexin and allowed to recover for 3, 7, 14, and 28 days under normoxia or hypobaric hypoxia (5,500 m) conditions. Hypoxia impaired the formation and growth of new myofibers and enhanced the loss of muscle mass during the first 7 days of regeneration, but did not affect the final recovery of muscle mass at 28 days. The impaired regeneration under hypoxic conditions was associated with a blunted activation of mechanical target of rapamycin (mTOR) signaling as assessed by p70(S6K) and 4E-BP1 phosphorylation that was independent of Akt activation. The decrease in mTOR activity with hypoxia was consistent with the increase in AMP-activated protein kinase activity, but not related to the change in regulated in development and DNA response 1 protein content. Hypoxia increased the mRNA levels of the atrogene muscle ring finger-1 after 7 days of regeneration, though muscle atrophy F box transcript levels remained unchanged. The increase in MyoD and myogenin mRNA expression with regeneration was attenuated at 7 days with hypoxia. In conclusion, our results support the notion that the enhanced loss of muscle mass observed after 1 week of regeneration under hypoxic conditions could mainly result from the impaired formation and growth of new fibers resulting from a reduction in protein synthesis and satellite cell activity.

  • 15.
    Chaillou, Thomas
    et al.
    University of Grenoble, Grenoble, France.
    Koulmann, N.
    Simler, N.
    Meunier, A.
    Grégoire, C.
    Chapot, R.
    Serrurier, B.
    Beaudry, M.
    Bigard, X.
    Ambient hypoxia enhances the muscle-mass loss after extensive injury2011Conference paper (Refereed)
  • 16.
    Chaillou, Thomas
    et al.
    Université Grenoble Alpes, Grenoble, France .
    Koulmann, N.
    Simler, N.
    Meunier, A.
    Grégoire, C.
    Serrurier, B.
    Beaudry, M.
    Bigard, X.
    Ambient hypoxia enhances the muscle-mass loss after extensive injury2011In: The FASEB Journal, ISSN 0892-6638, E-ISSN 1530-6860, Vol. 25, no 1 Suppl.Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to examine the effect of ambient hypoxia on the main intracellular pathways involved in muscle regeneration. Left soleus muscles of female rats were degenerated by notexin injection before exposure to either normoxia (N) or ambient hypoxia (H) (10% O2) during 3, 7, 14 and 28 days (d). The expected muscle-mass loss of injured muscles was higher in H than in N rats at d3 and d7, whereas the recovery of muscle mass was similar in H and N rats at d28. The mammalian target of rapamycin (mTOR) activity, assessed from both eIF-4E binding protein (4E-BP1) and P70S6K phosphorylation, was markedly increased during the early period of regeneration, but remained two-fold lower in H than in N groups at d3. The hypoxia-induced alteration of mTOR activity, independently of Akt, was associated with an activation of AMP-activated kinase (AMPK) at d3. In contrast, REDD1, another negative regulator of mTOR, was markedly activated by H at d14 and d28 in intact muscles, but was blunted during the first days of regeneration (d3–7), independently of H. Taken together, we show for the first time, that hypoxia enhances the muscle-mass loss after extensive injury. This could be due to a specific impairment of mTOR activation during muscle regeneration, independently of Akt, at least partly related to AMPK activation, without detectable effect of REDD1.

  • 17.
    Chaillou, Thomas
    et al.
    Örebro University, School of Health Sciences. Operational environments, Institut de Recherche Biomédicale des Armées, La Tronche, France.
    Koulmann, N.
    Operational environments, Institut de Recherche Biomédicale des Armées, La Tronche, France.
    Simler, N.
    Operational environments, Institut de Recherche Biomédicale des Armées, La Tronche, France.
    Meunier, A.
    Operational environments, Institut de Recherche Biomédicale des Armées, La Tronche, France.
    Serrurier, B.
    Operational environments, Institut de Recherche Biomédicale des Armées, La Tronche, France.
    Chapot, R.
    Operational environments, Institut de Recherche Biomédicale des Armées, La Tronche, France.
    Peinnequin, A.
    Genomic Core Facility, Institut de Recherche Biomédicale des Armées, La Tronche, France.
    Beaudry, M.
    Laboratoire “Réponses cellulaires et fonctionnelles a` l’hypoxie”, Université Paris, Bobigny, France.
    Bigard, X.
    Operational environments, Institut de Recherche Biomédicale des Armées, La Tronche, France.
    Hypoxia transiently affects skeletal muscle hypertrophy in a functional overload model2012In: American Journal of Physiology. Regulatory Integrative and Comparative Physiology, ISSN 0363-6119, E-ISSN 1522-1490, Vol. 302, p. R643-R654Article in journal (Refereed)
    Abstract [en]

    Hypoxia induces a loss of skeletal muscle mass, but the signaling pathways and molecular mechanisms involved remain poorly understood. We hypothesized that hypoxia could impair skeletal muscle hypertrophy induced by functional overload (Ov). To test this hypothesis, plantaris muscles were overloaded during 5, 12, and 56 days in female rats exposed to hypobaric hypoxia (5,500 m), and then, we examined the responses of specific signaling pathways involved in protein synthesis (Akt/mTOR) and breakdown (atrogenes). Hypoxia minimized the Ov-induced hypertrophy at days 5 and 12 but did not affect the hypertrophic response measured at day 56. Hypoxia early reduced the phosphorylation levels of mTOR and its downstream targets P70(S6K) and rpS6, but it did not affect the phosphorylation levels of Akt and 4E-BP1, in Ov muscles. The role played by specific inhibitors of mTOR, such as AMPK and hypoxia-induced factors (i.e., REDD1 and BNIP-3) was studied. REDD1 protein levels were reduced by overload and were not affected by hypoxia in Ov muscles, whereas AMPK was not activated by hypoxia. Although hypoxia significantly increased BNIP-3 mRNA levels at day 5, protein levels remained unaffected. The mRNA levels of the two atrogenes MURF1 and MAFbx were early increased by hypoxia in Ov muscles. In conclusion, hypoxia induced a transient alteration of muscle growth in this hypertrophic model, at least partly due to a specific impairment of the mTOR/P70(S6K) pathway, independently of Akt, by an undefined mechanism, and increased transcript levels for MURF1 and MAFbx that could contribute to stimulate the proteasomal proteolysis.

  • 18. Chaillou, Thomas
    et al.
    Koulmann, N.
    Simler, N.
    Serrurier, B.
    Meunier, A.
    Chapot, R.
    Peinnequin, A.
    Beaudry, M.
    Bigard, X.
    Ambient hypoxia transiently affects muscle growth in a functional overload model in rats2010Conference paper (Refereed)
  • 19. Chaillou, Thomas
    et al.
    Koulmann, N.
    Simler, N.
    Serrurier, B.
    Meunier, A.
    Chapot, R.
    Peinnequin, A.
    Beaudry, M.
    Bigard, X.
    Ambient hypoxia transiently affects muscle growth in a functional overload model in rats2011Conference paper (Refereed)
  • 20.
    Chaillou, Thomas
    et al.
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Lanner, Johanna T.
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Regulation of myogenesis and skeletal muscle regeneration: effects of oxygen levels on satellite cell activity2016In: The FASEB Journal, ISSN 0892-6638, E-ISSN 1530-6860, Vol. 30, no 12, p. 3929-3941Article, review/survey (Refereed)
    Abstract [en]

    Reduced oxygen (O2) levels (hypoxia) are present during embryogenesis and exposure to altitude and in pathologic conditions. During embryogenesis, myogenic progenitor cells reside in a hypoxic microenvironment, which may regulate their activity. Satellite cells are myogenic progenitor cells localized in a local environment, suggesting that the O2 level could affect their activity during muscle regeneration. In this review, we present the idea that O2 levels regulate myogenesis and muscle regeneration, we elucidate the molecular mechanisms underlying myogenesis and muscle regeneration in hypoxia and depict therapeutic strategies using changes in O2 levels to promote muscle regeneration. Severe hypoxia (≤1% O2) appears detrimental for myogenic differentiation in vitro, whereas a 3-6% O2 level could promote myogenesis. Hypoxia impairs the regenerative capacity of injured muscles. Although it remains to be explored, hypoxia may contribute to the muscle damage observed in patients with pathologies associated with hypoxia (chronic obstructive pulmonary disease, and peripheral arterial disease). Hypoxia affects satellite cell activity and myogenesis through mechanisms dependent and independent of hypoxia-inducible factor-1α. Finally, hyperbaric oxygen therapy and transplantation of hypoxia-conditioned myoblasts are beneficial procedures to enhance muscle regeneration in animals. These therapies may be clinically relevant to treatment of patients with severe muscle damage.-Chaillou, T. Lanner, J. T. Regulation of myogenesis and skeletal muscle regeneration: effects of oxygen levels on satellite cell activity.

  • 21.
    Chaillou, Thomas
    et al.
    Operational environments, IRBA La Tronche, La Tronche, France.
    Malgoyre, A.
    Operational environments, IRBA La Tronche, La Tronche, France.
    Banzet, S.
    Operational environments, IRBA La Tronche, La Tronche, France.
    Chapot, R.
    Operational environments, IRBA La Tronche, La Tronche, France.
    Koulmann, N.
    Operational environments, IRBA La Tronche, La Tronche, France.
    Pugnière, P.
    Genomic Core Facility, IRBA La Tronche, La Tronche, France.
    Beaudry, M.
    Laboratoire Réponses Cellulaires et Fonctionnelles À l'Hypoxie, Université Paris, Bobigny, France.
    Bigard, X.
    Operational environments, IRBA La Tronche, La Tronche, France.
    Peinnequin, A.
    Genomic Core Facility, IRBA La Tronche, La Tronche, France.
    Pitfalls in target mRNA quantification for real-time quantitative RT-PCR in overload-induced skeletal muscle hypertrophy2011In: Physiological Genomics, ISSN 1094-8341, E-ISSN 1531-2267, Vol. 43, no 4, p. 228-235Article in journal (Refereed)
    Abstract [en]

    Quantifying target mRNA using real-time quantitative reverse transcription-polymerase chain reaction requires an accurate normalization method. Determination of normalization factors (NFs) based on validated reference genes according to their relative stability is currently the best standard method in most usual situations. This method controls for technical errors, but its physiological relevance requires constant NF values for a fixed weight of tissue. In the functional overload model, the increase in the total RNA concentration must be considered in determining the NF values. Here, we pointed out a limitation of the classical geNorm-derived normalization. geNorm software selected reference genes despite that the NF values extensively varied under experiment. Only the NF values calculated from four intentionally selected genes were constant between groups. However, a normalization based on these genes is questionable. Indeed, three out of four genes belong to the same functional class (negative regulator of muscle mass), and their use is physiological nonsense in a hypertrophic model. Thus, we proposed guidelines for optimizing target mRNA normalization and quantification, useful in models of muscle mass modulation. In our study, the normalization method by multiple reference genes was not appropriate to compare target mRNA levels between overloaded and control muscles. A solution should be to use an absolute quantification of target mRNAs per unit weight of tissue, without any internal normalization. Even if the technical variations will stay present as a part of the intergroup variations, leading to less statistical power, we consider this method acceptable because it will not generate misleading results.

  • 22.
    Chaillou, Thomas
    et al.
    Örebro University, School of Health Sciences. Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    McPeek, Ashley
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Lanner, Johanna T.
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Docetaxel does not impair skeletal muscle force production in a murine model of cancer chemotherapy2017In: Physiological Reports, E-ISSN 2051-817X, Vol. 5, no 11, article id e13261Article in journal (Refereed)
    Abstract [en]

    Chemotherapy drugs such as docetaxel are commonly used to treat cancer. Cancer patients treated with chemotherapy experience decreased physical fitness, muscle weakness and fatigue. To date, it is unclear whether these symptoms result only from cancer-derived factors or from the combination of cancer disease and cancer treatments, such as chemotherapy. In this study, we aimed at determining the impact of chemotherapy per se on force production of hind limb muscles from healthy mice treated with docetaxel. We hypothesized that docetaxel will decrease maximal force, exacerbate the force decline during repeated contractions and impair recovery after fatiguing stimulations. We examined the function of soleus and extensor digitorum longus (EDL) muscles 24h and 72h after a single injection of docetaxel (acute treatment), and 7days after the third weekly injection of docetaxel (repeated treatment). Docetaxel was administrated by intravenous injection (20mg/kg) in female FVB/NRj mice and control mice were injected with saline solution. Our results show that neither acute nor repeated docetaxel treatment significantly alters force production during maximal contractions, repeated contractions or recovery. Only a tendency to decreased peak specific force was observed in soleus muscles 24h after a single injection of docetaxel (-17%, P=0.13). In conclusion, docetaxel administered intravenously does not impair force production in hind limb muscles from healthy mice. It remains to be clarified whether docetaxel, or other chemotherapy drugs, affect muscle function in subjects with cancer and whether the side effects associated with chemotherapy (neurotoxicity, central fatigue, decreased physical activity, etc.) are responsible for the experienced muscle weakness and fatigue.

  • 23.
    Chaillou, Thomas
    et al.
    Örebro University, School of Health Sciences.
    Montiel Rojas, Diego
    Örebro University, School of Health Sciences.
    Does the blunted stimulation of skeletal muscle protein synthesis by aging in response to mechanical load result from impaired ribosome biogenesis?2023In: Frontiers in aging, E-ISSN 2673-6217, Vol. 4, article id 1171850Article, review/survey (Refereed)
    Abstract [en]

    Age-related loss of skeletal muscle mass leads to a reduction of strength. It is likely due to an inadequate stimulation of muscle protein synthesis (MPS) in response to anabolic stimuli, such as mechanical load. Ribosome biogenesis is a major determinant of translational capacity and is essential for the control of muscle mass. This mini-review aims to put forth the hypothesis that ribosome biogenesis is impaired by aging in response to mechanical load, which could contribute to the age-related anabolic resistance and progressive muscle atrophy. Recent animal studies indicate that aging impedes muscle hypertrophic response to mechanical overload. This is associated with an impaired transcription of ribosomal DNA (rDNA) by RNA polymerase I (Pol I), a limited increase in total RNA concentration, a blunted activation of AKT/mTOR pathway, and an increased phosphorylation of AMPK. In contrast, an age-mediated impairment of ribosome biogenesis is unlikely in response to electrical stimulations. In human, the hypertrophic response to resistance exercise training is diminished with age. This is accompanied by a deficit in long-term MPS and an absence of increased total RNA concentration. The results addressing the acute response to resistance exercise suggest an impaired Pol I-mediated rDNA transcription and attenuated activation/expression of several upstream regulators of ribosome biogenesis in muscles from aged individuals. Altogether, emerging evidence indicates that impaired ribosome biogenesis could partly explain age-related anabolic resistance to mechanical load, which may ultimately contribute to progressive muscle atrophy. Future research should develop more advanced molecular tools to provide in-depth analysis of muscle ribosome biogenesis.

  • 24.
    Chaillou, Thomas
    et al.
    Örebro University, School of Health Sciences.
    Sanna, Igor
    Department of Health Sciences, Örebro University, Örebro, Sweden.
    Kadi, Fawzi
    Örebro University, School of Health Sciences.
    Glutamine-stimulated in vitro hypertrophy is preserved in muscle cells from older women2020In: Mechanisms of Ageing and Development, ISSN 0047-6374, E-ISSN 1872-6216, Vol. 187, article id 111228Article in journal (Refereed)
    Abstract [en]

    Age-related loss of muscle mass may result from reduced protein synthesis stimulation in response to anabolic stimuli, such as amino acid (AA) supplementation. The exact etiology of anabolic resistance to AA remains unclear. Therefore, the aim of this study was to investigate the anabolic response [cell size, protein synthesis and mechanistic target of rapamycin (mTOR) pathway] to the AA glutamine (a strong anabolic AA highly present in skeletal muscle) in myotubes obtained from 8 young (YW; 21-35 yrs) and 8 older (OW; 65-70 yrs) healthy women. This in vitro model of human primary myogenic cells explores the intrinsic behavior of muscle cells, while excluding potential influences of external factors. We showed that despite lower muscle mass, strength and cardiorespiratory fitness in OW compared to YW, myotube size (myotube diameter and area) and protein synthesis were not altered in OW, and glutamine-induced myotube hypertrophy and protein synthesis were preserved in OW. Apart from a lower glutamine-induced increase in P70S6 kinase phosphorylation in OW, no significant differences in other components of the mTOR pathway were observed between groups. Altogether, our data support the idea that the intrinsic capacity of muscle cells to respond to glutamine stimulation is preserved in healthy older women.

  • 25.
    Chaillou, Thomas
    et al.
    Örebro University, School of Health Sciences.
    Treigyte, Viktorija
    Sports Science and Innovation Institute, Lithuanian Sports University, Kaunas, Lithuania.
    Cold water immersion puts the chill on muscle protein synthesis after resistance exercise2020In: Journal of Physiology, ISSN 0022-3751, E-ISSN 1469-7793, Vol. 598, no 6, p. 1123-1124Article in journal (Refereed)
  • 26.
    Chaillou, Thomas
    et al.
    Örebro University, School of Health Sciences.
    Treigyte, Viktorija
    Eimantas, Nerijus
    Venckunas, Tomas
    Brazaitis, Marius
    Impact of acute and prolonged cooling on skeletal muscle force in young males2022Conference paper (Refereed)
    Abstract [en]

    Introduction

    In athletes, exposure to cold during winter sports may impair physical performance. Severe muscle cooling appears to reduce maximal force and induces a shift towards a slower contractile profile. However, whether moderate muscle cooling and the duration of cooling affect muscle contractile profile (assessed from electrically evoked torque at low and high frequencies) and maximal voluntary force (isometric and isokinetic contractions) remains to be clarified. Therefore, the aim of this study was to investigate the impact of acute and prolonged cooling on electrically evoked torque and maximal voluntary contraction torque in young males. 

    Methods

    Twelve active males (27.2 ± 6.6 years old) were recruited for this study, consisting of 2 phases: acute and prolonged exposures. During each phase, participants were randomly exposed to cold water immersion (CWI, 10°C, up to the iliac crest) or passive resting (PR). Exposure to CWI was either continuous during 45min (acute CWI, A-CWI) or intermittent during a period of 300min [prolonged CWI (P-CWI) including immersions between baseline to 45min, 165 to 180min, and 255 to 270min]. Muscle (Tmu, average across 1, 2 and 3cm depth) and rectal (Trec) temperatures were assessed using thermo-sensors. Transcutaneous electrical stimulation of the quadriceps muscle was performed to determine torques at low (20 Hz: P20) and high (100 Hz: P100) frequencies, and P20/P100 ratio was calculated. Maximal voluntary isometric torque of the knee extensors (MVIC), as well as peak isokinetic torques (90°/s) of knee extensors (KE-IsoC) and flexors (KF-isoC) were determined. Neuromuscular tests were performed at baseline (BL) and 60min after BL during acute exposure, and at BL, 60, 90, 150 and 300min after BL during prolonged exposure.

    Results

    Trec did not change after A-CWI while it was reduced (0.8 ± 0.4°C, p<0.001) after P-CWI compared to BL. Tmu decreased during A-CWI and P-CWI compared to BL (6.1 ± 2.2°C and 4.6 ± 1.1°C, respectively, p<0.001), with larger reduction of Tmu after A-CWI than P-CWI (p<0.05). P20 was not affected by the conditions. P100 was lower after 60min in A-CWI and P-CWI compared to PR (p<0.05). After the last bath (60min in A-CWI and 300min in P-CWI), P100 was nearly significantly higher in A-CWI than P-CWI (p=0.05). P20/P100 was higher after 60min in A-CWI and P-CWI compared to PR (p<0.001), but this ratio was lower in P-CWI than A-CWI after the last bath (p<0.05). MVIC torque remained unchanged during A-CWI and P-CWI, while KE-IsoC and KF-IsoC torques were similarly reduced after A-CWI and P-CWI compared to PR (p<0.05).

    Conclusion

    Moderate muscle cooling preferentially impairs maximal force production of dynamic contractions, but not isometric contractions, regardless of exposure duration. A shift towards a slower contractile profile (i.e., increased P20/P100) is more evident after A-CWI than P-CWI, which may be partially explained by a larger reduction of Tmu rather than the exposure duration or reduced Trec.

  • 27.
    Chaillou, Thomas
    et al.
    Örebro University, School of Health Sciences.
    Treigyte, Viktorija
    Sports Science and Innovation Institute, Lithuanian Sports University, 44221, Kaunas, Lithuania.
    Mosely, Sarah
    Muscle Health Research Centre, School of Kinesiology and Health Sciences, Faculty of Health, York University, Toronto, M3J 1P3, Canada.
    Brazaitis, Marius
    Sports Science and Innovation Institute, Lithuanian Sports University, 44221, Kaunas, Lithuania.
    Venckunas, Tomas
    Sports Science and Innovation Institute, Lithuanian Sports University, 44221, Kaunas, Lithuania.
    Cheng, Arthur J
    Muscle Health Research Centre, School of Kinesiology and Health Sciences, Faculty of Health, York University, Toronto, M3J 1P3, Canada.
    Functional Impact of Post-exercise Cooling and Heating on Recovery and Training Adaptations: Application to Resistance, Endurance, and Sprint Exercise2022In: Sports medicine - open, ISSN 2199-1170, Vol. 8, no 1, article id 37Article in journal (Refereed)
    Abstract [en]

    The application of post-exercise cooling (e.g., cold water immersion) and post-exercise heating has become a popular intervention which is assumed to increase functional recovery and may improve chronic training adaptations. However, the effectiveness of such post-exercise temperature manipulations remains uncertain. The aim of this comprehensive review was to analyze the effects of post-exercise cooling and post-exercise heating on neuromuscular function (maximal strength and power), fatigue resistance, exercise performance, and training adaptations. We focused on three exercise types (resistance, endurance and sprint exercises) and included studies investigating (1) the early recovery phase, (2) the late recovery phase, and (3) repeated application of the treatment. We identified that the primary benefit of cooling was in the early recovery phase (< 1 h post-exercise) in improving fatigue resistance in hot ambient conditions following endurance exercise and possibly enhancing the recovery of maximal strength following resistance exercise. The primary negative impact of cooling was with chronic exposure which impaired strength adaptations and decreased fatigue resistance following resistance training intervention (12 weeks and 4-12 weeks, respectively). In the early recovery phase, cooling could also impair sprint performance following sprint exercise and could possibly reduce neuromuscular function immediately after endurance exercise. Generally, no benefits of acute cooling were observed during the 24-72-h recovery period following resistance and endurance exercises, while it could have some benefits on the recovery of neuromuscular function during the 24-48-h recovery period following sprint exercise. Most studies indicated that chronic cooling does not affect endurance training adaptations following 4-6 week training intervention. We identified limited data employing heating as a recovery intervention, but some indications suggest promise in its application to endurance and sprint exercise.

  • 28. Chaillou, Thomas
    et al.
    Zhang, X.
    McCarthy, J.
    Muscle-specific Ribosomal Protein L3-like Inhibits Myotube Growth2014Conference paper (Refereed)
  • 29.
    Chaillou, Thomas
    et al.
    Center for Muscle Biology, University of Kentucky, Lexington KY, USA; Department of Physiology, College of Medicine, University of Kentucky, Lexington, Kentucky.
    Zhang, Xiping
    Center for Muscle Biology, University of Kentucky, Lexington KY,USA; Department of Physiology, College of Medicine, University of Kentucky, Lexington, Kentucky.
    McCarthy, John J
    Center for Muscle Biology, University of Kentucky, Lexington, Kentucky; Department of Physiology, College of Medicine, University of Kentucky, Lexington, Kentucky.
    Expression of Muscle-Specific Ribosomal Protein L3-Like Impairs Myotube Growth2016In: Journal of Cellular Physiology, ISSN 0021-9541, E-ISSN 1097-4652, Vol. 231, no 9, p. 1894-1902Article in journal (Refereed)
    Abstract [en]

    The ribosome has historically been considered to have no cell-specific function but rather serve in a "housekeeping" capacity. This view is being challenged by evidence showing that heterogeneity in the protein composition of the ribosome can lead to the functional specialization of the ribosome. Expression profiling of different tissues revealed that ribosomal protein large 3-like (Rpl3l) is exclusively expressed in striated muscle. In response to a hypertrophic stimulus, Rpl3l expression in skeletal muscle was significantly decreased by 82% whereas expression of the ubiquitous paralog Rpl3 was significantly increased by ∼fivefold. Based on these findings, we developed the hypothesis that Rpl3l functions as a negative regulator of muscle growth. To test this hypothesis, we used the Tet-On system to express Rpl3l in myoblasts during myotube formation. In support of our hypothesis, RPL3L expression significantly impaired myotube growth as assessed by myotube diameter (-23%) and protein content (-14%). Further analysis showed that the basis of this impairment was caused by a significant decrease in myoblast fusion as the fusion index was significantly lower (-17%) with RPL3L expression. These findings are the first evidence to support the novel concept of ribosome specialization in skeletal muscle and its role in the regulation of skeletal muscle growth.

  • 30.
    Cheng, A
    et al.
    Karolinska Institutet, Stockholm, Sweden.
    Allodi, I
    Karolinska Institutet, Stockholm, Sweden.
    Chaillou, Thomas
    Karolinska Institutet, Stockholm, Sweden.
    Thams, S
    Karolinska Institutet, Stockholm, Sweden.
    Ivarsson, N
    Karolinska Institutet, Stockholm, Sweden.
    Schlittler, M
    Karolinska Institutet, Stockholm, Sweden.
    Lanner, J
    Karolinska Institutet, Stockholm, Sweden.
    Hedlund, E
    Karolinska Institutet, Stockholm, Sweden.
    Andersson, D
    Karolinska Institutet, Stockholm, Sweden.
    Increased fatigue resistance and preserved specific force in intact single muscle fibres from the SOD1G93A mouse model of ALS2017In: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 219, no S710, p. 17-17, article id P-28Article in journal (Refereed)
    Abstract [en]

    Introduction: Amyotrophic lateral sclerosis (ALS) is a motor neurone disease characterized by degeneration and loss of motor neurones, leading to severe muscle weakness and paralysis. Although motor neurone degeneration is already a well-characterized symptom that contributes to muscle weakness in the SOD1G93A mouse model of ALS, the purpose of the current study was to determine whether muscle weakness in ALS can be attributed to impaired intrinsic force generation in skeletal muscles of SOD1G93A mice.

    Methods: Experiments were performed on whole muscles and mechanically dissected intact single fibres from the flexor digitorum brevis (FDB) muscle of SOD1G93A mice at three age groups of 50, 125 and 150 days of age (P50, P125 and P150). Myoplasmic free [Ca2+] ([Ca2+]i) was measured using the fluorescent indicator, indo-1.

    Results: Motor neurone loss and decreased force were evident in whole FDB muscles of P125–150 mice. In the intact single muscle fibres however, specific force, tetanic [Ca2+]iand resting [Ca2+]i were similar in single FDB fibres from symptomatic P125–150 SOD1G93A and age-matched wild-type littermates. The most intriguing finding was a markedly greater fatigue resistance in single fibres from P125–150 SOD1G93A vs. wild-type mice, which was not present in asymptomatic young P50 SOD1G93A mice. No shift in fibre-type distribution was observed in whole FDB muscles to explain the increased fatigue resistance of single fibres from P125–150 SOD1G93A mice.

    Conclusion: These results support the hypothesis that muscle weakness in ALS is not attributed to intrinsicdefects in skeletal muscle fibre force generation.

  • 31.
    Cheng, Arthur
    et al.
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Chaillou, Thomas
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Gineste, Charlotte
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Schlittler, Maja
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Intracellular Ca(2+) handling and myofibrillar Ca(2+) sensitivity are defective in single muscle fibres of aged humans2015In: Journal of Physiology, ISSN 0022-3751, E-ISSN 1469-7793, Vol. 593, no 15, p. 3237-3238Article in journal (Refereed)
  • 32.
    Cheng, Arthur J.
    et al.
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden; School of Kinesiology and Health Sciences, York University, Toronto, Canada.
    Allodi, Ilary
    Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Chaillou, Thomas
    Örebro University, School of Health Sciences. Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Schlittler, Maja
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden; Sports Science and Innovation Institute, Lithuanian Sports University, Kaunas, Lithuania.
    Ivarsson, Niklas
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Lanner, Johanna T.
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Thams, Sebastian
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Hedlund, Eva
    Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Andersson, Daniel C.
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden; Heart and Vascular Theme; Section for Heart Failure, Arrhythmia and GUCH; Karolinska University Hospital, Stockholm, Sweden.
    Intact single muscle fibres from SOD1(G93A) amyotrophic lateral sclerosis mice display preserved specific force, fatigue resistance and training-like adaptations2019In: Journal of Physiology, ISSN 0022-3751, E-ISSN 1469-7793, Vol. 597, no 12, p. 3133-3146Article in journal (Refereed)
    Abstract [en]

    Key points:

    • How defects in muscle contractile function contribute to weakness in amyotrophic lateral sclerosis (ALS) were systematically investigated.
    • Weakness in whole muscles from late stage SOD1G93A mice was explained by muscle atrophy as seen by reduced mass and maximal force.
    • On the other hand, surviving single muscle fibres in late stage SOD1G93A have preserved intracellular Ca2+ handling, normal force-generating capacity and increased fatigue resistance.
    • These intriguing findings provide a substrate for therapeutic interventions to potentiate muscular capacity and delay the progression of the ALS phenotype.

    Amyotrophic lateral sclerosis (ALS) is a motor neuron disease characterized by degeneration and loss of motor neurons, leading to severe muscle weakness and paralysis. The SOD1G93A mouse model of ALS displays motor neuron degeneration and a phenotype consistent with human ALS. The purpose of this study was to determine whether muscle weakness in ALS can be attributed to impaired intrinsic force generation in skeletal muscles. In the current study, motor neuron loss and decreased force were evident in whole flexor digitorum brevis (FDB) muscles of mice in the late stage of disease (125–150 days of age). However, in intact single muscle fibres, specific force, tetanic myoplasmic free [Ca2+] ([Ca2+]i), and resting [Ca2+]i remained unchanged with disease. Fibre-type distribution was maintained in late-stage SOD1G93A FDB muscles, but remaining muscle fibres displayed greater fatigue resistance compared to control and showed increased expression of myoglobin and mitochondrial respiratory chain proteins that are important determinants of fatigue resistance. Expression of genes central to both mitochondrial biogenesis and muscle atrophy where increased, suggesting that atrophic and compensatory adaptive signalling occurs simultaneously within the muscle tissue. These results support the hypothesis that muscle weakness in SOD1G93A is primarily attributed to neuromuscular degeneration and not intrinsic muscle fibre defects. In fact, surviving muscle fibres displayed maintained adaptive capacity with an exercise training-like phenotype, which suggests that compensatory mechanisms are activated that can function to delay disease progression.

  • 33.
    Cheng, Arthur J.
    et al.
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden; School of Kinesiology and Health Science, Faculty of Health, York University, Toronto, Canada, Ontario.
    Chaillou, Thomas
    Örebro University, School of Health Sciences.
    Kamandulis, Sigitas
    Sports Science and Innovation Institute, Lithuanian Sports University, Kaunas, Lithuania.
    Subocius, Andrejus
    Sports Science and Innovation Institute, Lithuanian Sports University, Kaunas, Lithuania; Department of Surgery, Kaunas Clinical Hospital, Kaunas, Lithuania; Clinic of Surgery, Republican Hospital of Kaunas, Kaunas, Lithuania.
    Westerblad, Håkan
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden; Sports Science and Innovation Institute, Lithuanian Sports University, Kaunas, Lithuania.
    Brazaitis, Marius
    Sports Science and Innovation Institute, Lithuanian Sports University, Kaunas, Lithuania.
    Venckunas, Tomas
    Sports Science and Innovation Institute, Lithuanian Sports University, Kaunas, Lithuania.
    Carbohydrates do not accelerate force recovery after glycogen-depleting followed by high-intensity exercise in humans2020In: Scandinavian Journal of Medicine and Science in Sports, ISSN 0905-7188, E-ISSN 1600-0838, Vol. 30, no 6, p. 998-1007Article in journal (Refereed)
    Abstract [en]

    Prolonged low-frequency force depression (PLFFD) induced by fatiguing exercise is characterized by a persistent depression in submaximal contractile force during the recovery period. Muscle glycogen depletion is known to limit physical performance during prolonged low- and moderate-intensity exercise, and accelerating glycogen re-synthesis with post-exercise carbohydrate intake can facilitate recovery and improve repeated bout exercise performance. Short-term, high-intensity exercise however, can cause PLFFD without any marked decrease in glycogen. Here we studied whether recovery from PLFFD was accelerated by carbohydrate ingestion after 60-min of moderate-intensity glycogen-depleting cycling exercise followed by six 30-s all-out cycling sprints. We used a randomized cross-over study design where nine recreationally-active males drank a beverage containing either carbohydrate or placebo after exercise. Blood glucose and muscle glycogen concentrations were determined at baseline, immediately post-exercise, and during the 3-h recovery period. Transcutaneous electrical stimulation of the quadriceps muscle was performed to determine the extent of PLFFD by eliciting low-frequency (20Hz) and high-frequency (100Hz) stimulations. Muscle glycogen was severely depleted after exercise, with a significantly higher rate of muscle glycogen re-synthesis during the 3-h recovery period in the carbohydrate than in the placebo trials (13.7 and 5.4 mmol glucosyl units/kg wet weight/h, respectively). Torque at 20Hz was significantly more depressed than 100 Hz torque during the recovery period in both conditions, and the extent of PLFFD (20/100Hz ratio) was not different between the two trials. In conclusion, carbohydrate supplementation enhances glycogen re-synthesis after glycogen-depleting exercise but does not improve force recovery when the exercise also involves all-out cycling sprints.

  • 34.
    Cheng, Arthur J.
    et al.
    Karolinska Institutet, Stockholm, Sweden.
    Willis, Sarah J.
    Swedish Winter Sports Research Centre, Mid Sweden University, Östersund, Sweden.
    Zinner, Christoph
    Swedish Winter Sports Research Centre, Mid Sweden University, Östersund, Sweden.
    Chaillou, Thomas
    Örebro University, School of Health Sciences. Karolinska Institutet, Stockholm, Sweden.
    Ivarsson, Niklas
    Karolinska Institutet, Stockholm, Sweden.
    Ørtenblad, Niels
    University of Southern Denmark, Odense, Denmark.
    Lanner, Johanna T.
    Karolinska Institutet, Stockholm, Sweden.
    Holmberg, Hans-Christer
    Karolinska Institutet, Stockholm, Sweden; Swedish Winter Sports Research Centre, Mid Sweden University, Östersund, Sweden.
    Westerblad, Håkan
    Karolinska Institutet, Stockholm, Sweden.
    Post-exercise recovery of contractile function and endurance in humans and mice is accelerated by heating and slowed by cooling skeletal muscle2017In: Journal of Physiology, ISSN 0022-3751, E-ISSN 1469-7793, Vol. 595, no 24, p. 7413-7426Article in journal (Refereed)
    Abstract [en]

    Manipulation of muscle temperature is believed to improve post-exercise recovery, with cooling being especially popular among athletes. However, it is unclear whether such temperature manipulations actually have positive effects. Accordingly, we studied the effect of muscle temperature on the acute recovery of force and fatigue resistance after endurance exercise. One hour of moderate-intensity arm cycling exercise in humans was followed by two hours recovery in which the upper arms were either heated to 38°C, not treated (33°C), or cooled to ∼15°C. Fatigue resistance after the recovery period was assessed by performing 3 × 5 min sessions of all-out arm cycling at physiological temperature for all conditions (i.e. not heated or cooled). Power output during the all-out exercise was better maintained when muscles were heated during recovery, whereas cooling had the opposite effect. Mechanisms underlying the temperature-dependent effect on recovery were tested in mouse intact single muscle fibres, which were exposed to ∼12 min of glycogen-depleting fatiguing stimulation (350 ms tetani given at 10 s interval until force decreased to 30% of the starting force). Fibres were subsequently exposed to the same fatiguing stimulation protocol after 1-2 h of recovery at 16-36°C. Recovery of submaximal force (30 Hz), the tetanic myoplasmic free [Ca(2+) ] (measured with the fluorescent indicator indo-1), and fatigue resistance were all impaired by cooling (16-26°C) and improved by heating (36°C). In addition, glycogen resynthesis was faster at 36°C than 26°C in whole FDB muscles. We conclude that recovery from exhaustive endurance exercise is accelerated by raising and slowed by lowering muscle temperature.

  • 35.
    Ferreira, DMS
    et al.
    Karolinska Institutet, Stockholm, Sweden.
    Cheng, AJ
    Karolinska Institutet, Stockholm, Sweden.
    Edsgärd, D
    Royal Institute of Technology (KTH), Stockholm, Sweden.
    Chaillou, Thomas
    Karolinska Institutet, Stockholm, Sweden.
    Porsmyr-Palmertz, M
    Karolinska Institutet, Stockholm, Sweden.
    da Silva, P
    Karolinska Institutet, Stockholm, Sweden.
    Izadi, M
    Karolinska Institutet, Stockholm, Sweden.
    Agudelo, L
    Karolinska Institutet, Stockholm, Sweden.
    Martínez-Redondo, V
    Karolinska Institutet, Stockholm, Sweden.
    Petersson-Klein, A
    Ruas, J
    LMCD1B: A novel regulator of skeletal muscle metabolism2017Conference paper (Refereed)
  • 36.
    Ferreira, Duarte M. S.
    et al.
    Molecular & Cellular Exercise Physiology, Department of Physiology and Pharmacology, Karolinska Institutet, Biomedicum, Stockholm, Sweden.
    Cheng, Arthur J.
    Molecular Muscle Physiology and Pathophysiology, Department of Physiology and Pharmacology, Karolinska Institutet, Biomedicum, Stockholm, Sweden; Faculty of Health, York University, School of Kinesiology and Health Science, Toronto, Ontario, Canada.
    Agudelo, Leandro Z.
    Molecular & Cellular Exercise Physiology, Department of Physiology and Pharmacology, Karolinska Institutet, Biomedicum, Stockholm, Sweden; Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, MA, USA.
    Cervenka, Igor
    Molecular & Cellular Exercise Physiology, Department of Physiology and Pharmacology, Karolinska Institutet, Biomedicum, Stockholm, Sweden.
    Chaillou, Thomas
    Örebro University, School of Health Sciences. Molecular Muscle Physiology and Pathophysiology, Department of Physiology and Pharmacology, Karolinska Institutet, Biomedicum, Stockholm, Sweden.
    Correia, Jorge C.
    Molecular & Cellular Exercise Physiology, Department of Physiology and Pharmacology, Karolinska Institutet, Biomedicum, Stockholm, Sweden.
    Porsmyr-Palmertz, Margareta
    Molecular & Cellular Exercise Physiology, Department of Physiology and Pharmacology, Karolinska Institutet, Biomedicum, Stockholm, Sweden.
    Izadi, Manizheh
    Molecular & Cellular Exercise Physiology, Department of Physiology and Pharmacology, Karolinska Institutet, Biomedicum, Stockholm, Sweden; Karp Research Building, Boston, MA, USA.
    Hansson, Alicia
    Molecular & Cellular Exercise Physiology, Department of Physiology and Pharmacology, Karolinska Institutet, Biomedicum, Stockholm, Sweden.
    Martínez-Redondo, Vicente
    Molecular & Cellular Exercise Physiology, Department of Physiology and Pharmacology, Karolinska Institutet, Biomedicum, Stockholm, Sweden.
    Valente-Silva, Paula
    Molecular & Cellular Exercise Physiology, Department of Physiology and Pharmacology, Karolinska Institutet, Biomedicum, Stockholm, Sweden.
    Pettersson-Klein, Amanda T.
    Molecular & Cellular Exercise Physiology, Department of Physiology and Pharmacology, Karolinska Institutet, Biomedicum, Stockholm, Sweden.
    Estall, Jennifer L.
    Division of Cardiovascular and Metabolic Disease, Institut de recherches cliniques de Montreal (IRCM), Montreal, QC, Canada.
    Robinson, Matthew M.
    Division of Endocrinology, Diabetes and Nutrition, Mayo Clinic, Rochester, MN, USA.
    Nair, K. Sreekumaran
    Division of Endocrinology, Diabetes and Nutrition, Mayo Clinic, Rochester, MN, USA.
    Lanner, Johanna T.
    Molecular Muscle Physiology and Pathophysiology, Department of Physiology and Pharmacology, Karolinska Institutet, Biomedicum, Stockholm, Sweden.
    Ruas, Jorge L
    Molecular & Cellular Exercise Physiology, Department of Physiology and Pharmacology, Karolinska Institutet, Biomedicum, Stockholm, Sweden.
    LIM and cysteine-rich domains 1 (LMCD1) regulates skeletal muscle hypertrophy, calcium handling, and force2019In: Skeletal Muscle, ISSN 2044-5040, Vol. 9, no 1, article id 26Article in journal (Refereed)
    Abstract [en]

    Background: Skeletal muscle mass and strength are crucial determinants of health. Muscle mass loss is associated with weakness, fatigue, and insulin resistance. In fact, it is predicted that controlling muscle atrophy can reduce morbidity and mortality associated with diseases such as cancer cachexia and sarcopenia.

    Methods: We analyzed gene expression data from muscle of mice or human patients with diverse muscle pathologies and identified LMCD1 as a gene strongly associated with skeletal muscle function. We transiently expressed or silenced LMCD1 in mouse gastrocnemius muscle or in mouse primary muscle cells and determined muscle/cell size, targeted gene expression, kinase activity with kinase arrays, protein immunoblotting, and protein synthesis levels. To evaluate force, calcium handling, and fatigue, we transduced the flexor digitorum brevis muscle with a LMCD1-expressing adenovirus and measured specific force and sarcoplasmic reticulum Ca2+ release in individual fibers. Finally, to explore the relationship between LMCD1 and calcineurin, we ectopically expressed Lmcd1 in the gastrocnemius muscle and treated those mice with cyclosporine A (calcineurin inhibitor). In addition, we used a luciferase reporter construct containing the myoregulin gene promoter to confirm the role of a LMCD1-calcineurin-myoregulin axis in skeletal muscle mass control and calcium handling.

    Results: Here, we identify LIM and cysteine-rich domains 1 (LMCD1) as a positive regulator of muscle mass, that increases muscle protein synthesis and fiber size. LMCD1 expression in vivo was sufficient to increase specific force with lower requirement for calcium handling and to reduce muscle fatigue. Conversely, silencing LMCD1 expression impairs calcium handling and force, and induces muscle fatigue without overt atrophy. The actions of LMCD1 were dependent on calcineurin, as its inhibition using cyclosporine A reverted the observed hypertrophic phenotype. Finally, we determined that LMCD1 represses the expression of myoregulin, a known negative regulator of muscle performance. Interestingly, we observed that skeletal muscle LMCD1 expression is reduced in patients with skeletal muscle disease.

    Conclusions: Our gain- and loss-of-function studies show that LMCD1 controls protein synthesis, muscle fiber size, specific force, Ca2+ handling, and fatigue resistance. This work uncovers a novel role for LMCD1 in the regulation of skeletal muscle mass and function with potential therapeutic implications.

  • 37. Ghaffar, Quratulain
    et al.
    Jude, Baptiste
    Lanner, Johanna
    Chaillou, Thomas
    Örebro University, School of Health Sciences.
    Muscle atrophy is associated with activated anabolic and catabolic pathways in a mouse model of rheumatoid arthritis2021Conference paper (Refereed)
  • 38.
    Gineste, Charlotte
    et al.
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden; Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Illkirch, France.
    Youhanna, Sonia
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Vorrink, Sabine U.
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Henriksson, Sara
    Umeå Core Facility for Electron Microscopy, Department of Chemistry, Umeå University, Umeå, Sweden.
    Hernández, Andrés
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden; University of California Merced, Merced CA, USA.
    Cheng, Arthur J.
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden; School of Kinesiology and Health Sciences, York University, Toronto, Canada.
    Chaillou, Thomas
    Örebro University, School of Health Sciences. Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Buttgereit, Andreas
    Institute of Medical Biotechnology, Department of Chemical and Biological Engineering, Friedrich- Alexander University of Erlangen-Nürnberg, Erlangen, Germany.
    Schneidereit, Dominik
    Institute of Medical Biotechnology, Department of Chemical and Biological Engineering, Friedrich- Alexander University of Erlangen-Nürnberg, Erlangen, Germany.
    Friedrich, Oliver
    Institute of Medical Biotechnology, Department of Chemical and Biological Engineering, Friedrich- Alexander University of Erlangen-Nürnberg, Erlangen, Germany.
    Hultenby, Kjell
    Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Huddinge, Sweden.
    Bruton, Joseph D.
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Ivarsson, Niklas
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Sandblad, Linda
    Umeå Core Facility for Electron Microscopy, Department of Chemistry, Umeå University, Umeå, Sweden.
    Lauschke, Volker M.
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden; Dr. Margarete Fischer- Bosch-Institute of Clinical Pharmacology, Stuttgart, Germany; University of Tuübingen, Tübingen, Germany.
    Westerblad, Håkan
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Enzymatically dissociated muscle fibers display rapid dedifferentiation and impaired mitochondrial calcium control2022In: iScience, E-ISSN 2589-0042 , Vol. 25, no 12, article id 105654Article in journal (Refereed)
    Abstract [en]

    Cells rapidly lose their physiological phenotype upon disruption of their extracellular matrix (ECM)-intracellular cytoskeleton interactions. By comparing adult mouse skeletal muscle fibers, isolated either by mechanical dissection or by collagenase-induced ECM digestion, we investigated acute effects of ECM disruption on cellular and mitochondrial morphology, transcriptomic signatures, and Ca2+ handling. RNA-sequencing showed striking differences in gene expression patterns between the two isolation methods with enzymatically dissociated fibers resembling myopathic phenotypes. Mitochondrial appearance was grossly similar in the two groups, but 3D electron microscopy revealed shorter and less branched mitochondria following enzymatic dissociation. Repeated contractions resulted in a prolonged mitochondrial Ca2+ accumulation in enzymatically dissociated fibers, which was partially prevented by cyclophilin inhibitors. Of importance, muscle fibers of mice with severe mitochondrial myopathy show pathognomonic mitochondrial Ca2+ accumulation during repeated contractions and this accumulation was concealed with enzymatic dissociation, making this an ambiguous method in studies of native intracellular Ca2+ fluxes.

  • 39.
    Järvinen, Laura
    et al.
    School of Health Sciences, Örebro University, Örebro, Sweden.
    Lundin Petersdotter, Sofi
    School of Health Sciences, Örebro University, Örebro, Sweden.
    Chaillou, Thomas
    Örebro University, School of Health Sciences.
    High-intensity resistance exercise is not as effective as traditional high-intensity interval exercise for increasing the cardiorespiratory response and energy expenditure in recreationally active subjects2022In: European Journal of Applied Physiology, ISSN 1439-6319, E-ISSN 1439-6327, Vol. 122, no 2, p. 459-474Article in journal (Refereed)
    Abstract [en]

    PURPOSE: Traditional high-intensity interval exercise (HIIE) highly stimulates the cardiorespiratory system and increases energy expenditure (EE) during exercise. High-intensity resistance exercise (HIRE) has become more popular in recreationally active subjects. The physiological responses to HIRE performed with light or moderate load is currently largely unknown. Here, we examined the effect of the type of interval exercise [HIRE at 40% (HIRE40) and 60% (HIRE60) 1-RM vs. traditional HIIE] on the cardiorespiratory response and EE during and after exercise.

    METHODS: Fifteen recreationally active adults randomly completed traditional HIIE on an ergocyle, HIRE40 and HIRE60. The sessions consisted of two sets of ten 30-s intervals (power at 100% VO2max during HIIE; maximal number of repetitions for 10 different free-weight exercises during HIRE40 and HIRE60) separated by 30-s active recovery periods. Gas exchange, heart rate (HR) and EE were assessed during and after exercise.

    RESULTS: VO2mean, VO2peak, HRmean, the time spent above 90% VO2max and HRmax, and aerobic EE were lower in both HIRE sessions compared with HIIE (P < 0.05). Anaerobic glycolytic contribution to total exercise EE was higher in HIRE40 and HIRE60 compared with HIIE (P < 0.001). EE from excess post-exercise oxygen consumption (EPOC) was similar after the three sessions. Overall, similar cardiorespiratory responses and EE were found in HIRE40 and HIRE60.

    CONCLUSIONS: HIRE is not as effective as HIIE for increasing the cardiorespiratory response and EE during exercise, while EPOC remains similar in HIRE and HIIE. These parameters are not substantially different between HIRE40 and HIRE60.

  • 40.
    Kamandulis, Sigitas
    et al.
    Institute of Sport Science and Innovations, Lithuanian Sports University, Kaunas, Lithuania.
    Mickevicius, Mantas
    Institute of Sport Science and Innovations, Lithuanian Sports University, Kaunas, Lithuania.
    Snieckus, Audrius
    Institute of Sport Science and Innovations, Lithuanian Sports University, Kaunas, Lithuania.
    Streckis, Vytautas
    Institute of Sport Science and Innovations, Lithuanian Sports University, Kaunas, Lithuania.
    Montiel Rojas, Diego
    Örebro University, School of Health Sciences.
    Chaillou, Thomas
    Örebro University, School of Health Sciences.
    Westerblad, Hakan
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Venckunas, Tomas
    Institute of Sport Science and Innovations, Lithuanian Sports University, Kaunas, Lithuania.
    Increasing the resting time between drop jumps lessens delayed-onset muscle soreness and limits the extent of prolonged low-frequency force depression in human knee extensor muscles2022In: European Journal of Applied Physiology, ISSN 1439-6319, E-ISSN 1439-6327, Vol. 122, no 1, p. 255-266Article in journal (Refereed)
    Abstract [en]

    PURPOSE: Unaccustomed eccentric contractions generally result in a long-lasting contractile impairment, referred to as prolonged low-frequency force depression (PLFFD), and delayed-onset muscle soreness (DOMS). We here used repeated drop jumps (DJs) as an eccentric contraction model and studied the effects of increasing the time between DJs from 20 s to 5 min. We hypothesized that both PLFFD and DOMS would be less marked at the longer DJ interval due to the longer time to restore structural elements between DJs.

    METHODS: Young men (n = 12) randomly performed 50 DJs with either 20-s (DJ-20 s) or 5-min (DJ-5 min) rest between DJs. Voluntary, 20 Hz and 100 Hz electrically stimulated isometric knee extension torques and muscle soreness were monitored before and for 7 days after DJs; serum CK activity was measured to assess muscle fibre protein leakage. In additional experiments, changes in mRNA levels were assessed in muscle biopsies collected before and 1 h after exercise.

    RESULTS: A marked PLFFD was observed with both protocols and the extent of 20 Hz torque depression was smaller immediately and 1 day after DJ-5 min than after DJ-20 s (p < 0.05), whereas the MVC and 100 Hz torques were similarly decreased with the two protocols. Markedly larger differences between the two protocols were observed for the muscle soreness score, which 1-4 days after exercise was about two times larger with DJ-20 s than with DJ-5 min (p < 0.01).

    CONCLUSIONS: The larger protective effect of the longer DJ interval against DOMS than against PLFFD indicates that their underlying mechanisms involve different structural elements.

  • 41.
    Kirby, T.J.
    et al.
    Center for Muscle Biology, University of Kentucky, Lexington KY, USA; Department of Physiology, College of Medicine, University of Kentucky, Lexington KY, USA.
    Chaillou, Thomas
    Center for Muscle Biology, University of Kentucky, Lexington KY, USA; Department of Physiology, College of Medicine, University of Kentucky, Lexington KY, USA.
    McCarthy, J.J.
    Center for Muscle Biology, University of Kentucky, Lexington KY, USA; Department of Physiology, College of Medicine, University of Kentucky, Lexington KY, USA.
    The role of microRNAs in skeletal muscle health and disease2015In: Frontiers in Bioscience, ISSN 1093-9946, E-ISSN 1093-4715, Vol. 20, p. 37-77Article in journal (Refereed)
    Abstract [en]

    Over the last decade non-coding RNAs have emerged as importance regulators of gene expression. In particular, microRNAs are a class of small RNAs of ∼ 22 nucleotides that repress gene expression through a post-transcriptional mechanism. MicroRNAs have been shown to be involved in a broader range of biological processes, both physiological and pathological, including myogenesis, adaptation to exercise and various myopathies. The purpose of this review is to provide a comprehensive summary of what is currently known about the role of microRNAs in skeletal muscle health and disease.

  • 42.
    Kirby, T.J.
    et al.
    Center for Muscle Biology, University of Kentucky, Lexington, Kentucky, USA; Department of Physiology, College of Medicine, University of Kentucky, Lexington, Kentucky, USA.
    Lee, J.D.
    Department of Physiology, College of Medicine, University of Kentucky, Lexington, Kentucky, USA; Department of Rehabilitation Sciences, College of Health Sciences, University of Kentucky, Lexington, Kentucky, USA; Department of Molecular and Integrative Physiology, Medical School, University of Michigan, Ann Arbor, Michigan, USA.
    England, J.H.
    Department of Physiology, College of Medicine University of Kentucky, Lexington, Kentucky, USA.
    Chaillou, Thomas
    Center for Muscle Biology, University of Kentucky, Lexington, Kentucky, USA; Department of Physiology, College of Medicine, University of Kentucky, Lexington, Kentucky, USA; Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Esser, K.A.
    Center for Muscle Biology, University of Kentucky, Lexington, Kentucky, USA; Department of Physiology, College of Medicine, University of Kentucky, Lexington, Kentucky, USA.
    McCarthy, J.J.
    Center for Muscle Biology, University of Kentucky, Lexington, Kentucky, USA; Department of Physiology, College of Medicine, University of Kentucky, Lexington, Kentucky, USA.
    Blunted hypertrophic response in aged skeletal muscle is associated with decreased ribosome biogenesis2015In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 119, no 4, p. 321-327Article in journal (Refereed)
    Abstract [en]

    The ability of skeletal muscle to hypertrophy in response to a growth stimulus is known to be compromised in older individuals. We hypothesized that a change in the expression of protein-encoding genes in response to a hypertrophic stimulus contributes to the blunted hypertrophy observed with aging. To test this hypothesis, we determined gene expression by microarray analysis of plantaris muscle from 5- and 25-mo-old mice subjected to 1, 3, 5, 7, 10, and 14 days of synergist ablation to induce hypertrophy. Overall, 1,607 genes were identified as being differentially expressed across the time course between young and old groups; however, the difference in gene expression was modest, with cluster analysis showing a similar pattern of expression between the two groups. Despite ribosome protein gene expression being higher in the aged group, ribosome biogenesis was significantly blunted in the skeletal muscle of aged mice compared with mice young in response to the hypertrophic stimulus (50% vs. 2.5-fold, respectively). The failure to upregulate pre-47S ribosomal RNA (rRNA) expression in muscle undergoing hypertrophy of old mice indicated that rDNA transcription by RNA polymerase I was impaired. Contrary to our hypothesis, the findings of the study suggest that impaired ribosome biogenesis was a primary factor underlying the blunted hypertrophic response observed in skeletal muscle of old mice rather than dramatic differences in the expression of protein-encoding genes. The diminished increase in total RNA, pre-47S rRNA, and 28S rRNA expression in aged muscle suggest that the primary dysfunction in ribosome biogenesis occurs at the level of rRNA transcription and processing.

  • 43.
    Lanner, Johanna
    et al.
    Karolinska Institutet, Stockholm, Sweden.
    Mader, Theresa
    Karolinska Institutet, Stockholm, Sweden.
    Chaillou, Thomas
    Örebro University, School of Health Sciences. Karolinska institutet, Stockholm, Sweden.
    Cheng, Arthur
    Karolinska Institutet, Stockholm, Sweden.
    Steinz, Marteen
    Karolinska Institutet, Stockholm, Sweden.
    Zhengye, Liu
    Karolinska Institutet, Stockholm, Sweden.
    Rundqvist, Helene
    Karolinska Institutet, Stockholm, Sweden.
    Kenne, Elinor
    Karolinska Institutet, Stockholm, Sweden.
    Running reverses tumor-induced muscle weakness in mice with breast cancer2019Conference paper (Refereed)
    Abstract [en]

    Introduction: Patients with breast cancer experience muscle dysfunction, which is a clinical challenge that is not restricted to advanced stage patients, but also observed in newly diagnosed weight-stable patients with low tumor burden. Recent data indicate that physical activity can reduce breast cancerassociated mortality, suggesting that improved muscle performance per secan have positive impact on survival. Here, the transgenic PyMT mouse model of breast cancer was used to elucidate molecular mechanisms underlying breast cancer-induced muscle impairments.

    Materials and Methods: PyMT mice and wildtype (WT) littermates w/wo access to an in-cage running wheel for four weeks (week 8-12). Functional readouts included Ca2+imaging; isometric force measurement on single fibers and intact fast-and slow-twitchmuscles. Intramuscular signaling was assessed using immunofluorescence, immunoblotting and enzymatic assays.

    Results: The specific force (i.e. force/cross-sectional area) was significantly decreased by ~ 35% in slow-twitch soleus muscles from breast cancermice as compared to WT muscles, which was the result of reduced Ca2+release and impaired myofibrillar function. There were no difference in muscle size or fiber type between the two groups. However, higher intramuscular stress (e.g. p38 activation and carbonylation (DNP)) was observed in PyMT than in WT. Intriguingly, voluntary running for four weeks reversed the weakness and PyMT soleus muscles generated similar forces as muscles of exercised WT mice. The running induced higher SOD2 expression and normalized levels of p38 and DNP.

    Conclusion: Intrinsic contractile dysfunction and higher intramuscular stress was present in mice with breast cancer, which was counteracted with voluntary running.

  • 44.
    Liu, Zhengye
    et al.
    Department of Physiology and Pharmacology, Molecular Muscle Physiology and Pathophysiology, Karolinska Institutet, Stockholm, Sweden.
    Chaillou, Thomas
    Örebro University, School of Health Sciences. Department of Physiology and Pharmacology, Molecular Muscle Physiology and Pathophysiology, Karolinska Institutet, Stockholm, Sweden.
    Santos Alves, Estela
    Department of Physiology and Pharmacology, Molecular Muscle Physiology and Pathophysiology, Karolinska Institutet, Stockholm, Sweden.
    Mader, Theresa
    Department of Physiology and Pharmacology, Molecular Muscle Physiology and Pathophysiology, Karolinska Institutet, Stockholm, Sweden.
    Jude, Baptiste
    Department of Physiology and Pharmacology, Molecular Muscle Physiology and Pathophysiology, Karolinska Institutet, Stockholm, Sweden.
    Ferreira, Duarte M. S.
    Department of Physiology and Pharmacology, Molecular and Cellular Exercise Physiology, Karolinska Institutet, Stockholm, Sweden.
    Hynynen, Heidi
    Department of Physiology and Pharmacology, Molecular and Cellular Exercise Physiology, Karolinska Institutet, Stockholm, Sweden.
    Cheng, Arthur J.
    Department of Physiology and Pharmacology, Molecular Muscle Physiology and Pathophysiology, Karolinska Institutet, Stockholm, Sweden.
    Jonsson, William O.
    Department of Physiology and Pharmacology, Molecular Muscle Physiology and Pathophysiology, Karolinska Institutet, Stockholm, Sweden.
    Pironti, Gianluigi
    Department of Physiology and Pharmacology, Medical Cardiac and Skeletal Muscle Research, Karolinska Institutet, Stockholm, Sweden.
    Andersson, Daniel C.
    Department of Physiology and Pharmacology, Medical Cardiac and Skeletal Muscle Research, Karolinska Institutet, Stockholm, Sweden; Heart, Vascular and Neurology Theme, Cardiology Unit, Karolinska University Hospital, Stockholm, Sweden.
    Kenne, Ellinor
    Department of Physiology and Pharmacology, Molecular Muscle Physiology and Pathophysiology, Karolinska Institutet, Stockholm, Sweden.
    Ruas, Jorge L.
    Department of Physiology and Pharmacology, Molecular and Cellular Exercise Physiology, Karolinska Institutet, Stockholm, Sweden.
    Tavi, Pasi
    A.I. Virtanen Institute, University of Eastern Finland, Kuopio, Finland.
    Lanner, Johanna T.
    Department of Physiology and Pharmacology, Molecular Muscle Physiology and Pathophysiology, Karolinska Institutet, Stockholm, Sweden.
    Mitochondrial NDUFA4L2 is a novel regulator of skeletal muscle mass and force2021In: The FASEB Journal, ISSN 0892-6638, E-ISSN 1530-6860, Vol. 35, no 12, article id e22010Article in journal (Refereed)
    Abstract [en]

    The hypoxia-inducible nuclear-encoded mitochondrial protein NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 4-like 2 (NDUFA4L2) has been demonstrated to decrease oxidative phosphorylation and production of reactive oxygen species in neonatal cardiomyocytes, brain tissue and hypoxic domains of cancer cells. Prolonged local hypoxia can negatively affect skeletal muscle size and tissue oxidative capacity. Although skeletal muscle is a mitochondrial rich, oxygen sensitive tissue, the role of NDUFA4L2 in skeletal muscle has not previously been investigated. Here we ectopically expressed NDUFA4L2 in mouse skeletal muscles using adenovirus-mediated expression and in vivo electroporation. Moreover, femoral artery ligation (FAL) was used as a model of peripheral vascular disease to induce hind limb ischemia and muscle damage. Ectopic NDUFA4L2 expression resulted in reduced mitochondrial respiration and reactive oxygen species followed by lowered AMP, ADP, ATP, and NAD(+) levels without affecting the overall protein content of the mitochondrial electron transport chain. Furthermore, ec-topically expressed NDUFA4L2 caused a similar to 20% reduction in muscle mass that resulted in weaker muscles. The loss of muscle mass was associated with increased gene expression of atrogenes MurF1 and Mul1, and apoptotic genes caspase 3 and Bax. Finally, we showed that NDUFA4L2 was induced by FAL and that the Ndufa4l2 mRNA expression correlated with the reduced capacity of the muscle to generate force after the ischemic insult. These results show, for the first time, that mitochondrial NDUFA4L2 is a novel regulator of skeletal muscle mass and force. Specifically, induced NDUFA4L2 reduces mitochondrial activity leading to lower levels of important intramuscular metabolites, including adenine nucleotides and NAD(+), which are hallmarks of mitochondrial dysfunction and hence shows that dysfunctional mitochondrial activity may drive muscle wasting.

  • 45.
    Mader, Theresa
    et al.
    Department of Physiology and Pharmacology, Molecular Muscle Physiology and Pathophysiology, Karolinska Institutet, Biomedicum, Stockholm, Sweden.
    Chaillou, Thomas
    Örebro University, School of Health Sciences. Department of Physiology and Pharmacology, Molecular Muscle Physiology and Pathophysiology, Karolinska Institutet, Biomedicum, Stockholm, Sweden.
    Alves, Estela Santos
    Department of Physiology and Pharmacology, Molecular Muscle Physiology and Pathophysiology, Karolinska Institutet, Biomedicum, Stockholm, Sweden.
    Jude, Baptiste
    Department of Physiology and Pharmacology, Molecular Muscle Physiology and Pathophysiology, Karolinska Institutet, Biomedicum, Stockholm, Sweden.
    Cheng, Arthur J.
    Department of Physiology and Pharmacology, Molecular Muscle Physiology and Pathophysiology, Karolinska Institutet, Biomedicum, Stockholm, Sweden; Muscle Health Research Centre, School of Kinesiology and Health Science, Faculty of Health Toronto, York University, Toronto, Ontario, Canada.
    Kenne, Ellinor
    Department of Physiology and Pharmacology, Molecular Muscle Physiology and Pathophysiology, Karolinska Institutet, Biomedicum, Stockholm, Sweden.
    Mijwel, Sara
    Department of Physiology and Pharmacology, Molecular Muscle Physiology and Pathophysiology, Karolinska Institutet, Biomedicum, Stockholm, Sweden; Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.
    Kurzejamska, Ewa
    Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
    Vincent, Clara Theresa
    Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden; Department of Microbiology, NYU Grossman School of Medicine, New York, NY, USA.
    Rundqvist, Helene
    Department of Laboratory Medicine, Clinical Physiology, Karolinska Institutet, Stockholm, Sweden.
    Lanner, Johanna T.
    Department of Physiology and Pharmacology, Molecular Muscle Physiology and Pathophysiology, Karolinska Institutet, Biomedicum, Stockholm, Sweden.
    Exercise reduces intramuscular stress and counteracts muscle weakness in mice with breast cancer2022In: Journal of Cachexia, Sarcopenia and Muscle, ISSN 2190-5991, E-ISSN 2190-6009, Vol. 13, no 2, p. 1151-1163Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Patients with breast cancer exhibit muscle weakness, which is associated with increased mortality risk and reduced quality of life. Muscle weakness is experienced even in the absence of loss of muscle mass in breast cancer patients, indicating intrinsic muscle dysfunction. Physical activity is correlated with reduced cancer mortality and disease recurrence. However, the molecular processes underlying breast cancer-induced muscle weakness and the beneficial effect of exercise are largely unknown.

    METHODS: Eight-week-old breast cancer (MMTV-PyMT, PyMT) and control (WT) mice had access to active or inactive in-cage voluntary running wheels for 4 weeks. Mice were also subjected to a treadmill test. Muscle force was measured ex vivo. Tumour markers were determined with immunohistochemistry. Mitochondrial biogenesis and function were assessed with transcriptional analyses of PGC-1α, the electron transport chain (ETC) and antioxidants superoxide dismutase (Sod) and catalase (Cat), combined with activity measurements of SOD, citrate synthase (CS) and β-hydroxyacyl-CoA-dehydrogenase (βHAD). Serum and intramuscular stress levels were evaluated by enzymatic assays, immunoblotting, and transcriptional analyses of, for example, tumour necrosis factor-α (TNF-α) and p38 mitogen-activated protein kinase (MAPK) signalling.

    RESULTS: PyMT mice endured shorter time and distance during the treadmill test (~30%, P < 0.05) and ex vivo force measurements revealed ~25% weaker slow-twitch soleus muscle (P < 0.001). This was independent of cancer-induced alteration of muscle size or fibre type. Inflammatory stressors in serum and muscle, including TNF-α and p38 MAPK, were higher in PyMT than in WT mice (P < 0.05). Cancer-induced decreases in ETC (P < 0.05, P < 0.01) and antioxidant gene expression were observed (P < 0.05). The exercise intervention counteracted the cancer-induced muscle weakness and was accompanied by a less aggressive, differentiated tumour phenotype, determined by increased CK8 and reduced CK14 expression (P < 0.05). In PyMT mice, the exercise intervention led to higher CS activity (P = 0.23), enhanced β-HAD and SOD activities (P < 0.05), and reduced levels of intramuscular stressors together with a normalization of the expression signature of TNFα-targets and ETC genes (P < 0.05, P < 0.01). At the same time, the exercise-induced PGC-1α expression, and CS and β-HAD activity was blunted in muscle from the PyMT mice as compared with WT mice, indicative that breast cancer interfere with transcriptional programming of mitochondria and that the molecular adaptation to exercise differs between healthy mice and those afflicted by disease.

    CONCLUSIONS: Four-week voluntary wheel running counteracted muscle weakness in PyMT mice which was accompanied by reduced intrinsic stress and improved mitochondrial and antioxidant profiles and activities that aligned with muscles of healthy mice.

  • 46.
    Mader, Theresa
    et al.
    Karolinska Institutet, Solna, Sweden.
    Kenne, Ellinor
    Karolinska Institutet, Solna, Sweden.
    Chaillou, Thomas
    Örebro University, School of Health Sciences.
    Petkovic, Monika
    Karolinska Institutet, Solna, Sweden.
    Steinz, Maarten
    Karolinska Institutet, Solna, Sweden.
    Liu, Zhengye
    Karolinska Institutet, Solna, Sweden.
    Kalakoutis, Michaeljohn
    Karolinska Institutet, Solna, Sweden.
    Lanner, Johanna
    Karolinska Institutet, Solna, Sweden.
    Metabolic alteration and muscle dysfunction in mice with breast cancer2018Conference paper (Refereed)
    Abstract [en]

    Breast cancer accounts for ~25% of diagnosed cancer types in woman [1]. Decreased physical fitness and muscle weakness are common complications in patients with breast cancer. In cancer, muscle weakness has traditionally been linked to muscle wasting and significant weight loss (cachexia) [2]. However, muscle weakness is present in non-cachectic, weight-stable patients with breast cancer [3]. In fact, cancer-induced muscle dysfunction is a broad clinical challenge that is not restricted to palliative or advanced stage patients, but also observed in newly diagnosed patients with low tumor burden [4]. Further, with the breast cancer treatment improving, it is important to take a look on the patients quality of life [5]. However, little is known about the features underlying breast cancer-induced muscle impairments and no drug preventing cancer-induced muscle weakness is clinically proven. Here we aim at characterizing the metabolic status and the muscle function in mice with breast cancer.

    The breast cancer mouse-model MMTV-PyMT (PyMT) used here, is characterized by an early onset of mammary cancer (from 5 weeks of age) and follows a similar progression pattern as the one observed in human patients [6]. Soleus muscle from PyMT mice exhibited ~30% lower specific force (kN/m2) than soleus muscle from wildtype (WT) mice (n=28-29, p ≤ 0.05, mice were 12 week old at sacrifice). There were no significant differences in muscle mass, fiber size or fiber type distribution between PyMT and WT muscle. Furthermore, there were no differences in glycogen content (μg/g muscle) in soleus muscle from PyMT and WT mice. Simultaneous measurement of numerous parameters (e.g. oxygen consumption (VO2), carbon dioxide production (VCO2), and food and water intake) was carried out using comprehensive lab animal monitoring system (CLAMS) to gain insight into the metabolic status of the mice. The mice were monitored over a week and the average respiratory exchange ratio (RER = CO2production: O2 uptake) were significantly differed between PyMT and WT mice, with mean PyMT RER of 0.95±0.01 and WT RER of 1.0±0.01 (mean data +/-SEM, n=8, p<0.001). Thus, indicative that PyMT have an altered metabolism towards fatty acid utilization.

    In summary, soleus muscles are weaker and the whole-body metabolism appears altered in mice with breast cancer as compared with healthy control mice. Gene and molecular analysis are currently being performed to further assess mitochondrial and glucose metabolism. Nevertheless, further studies are needed to gain insight into cancer-derived factors that contributes to skeletal muscle dysfunction and altered metabolism.

    1. Jemal, A., et al., Cancer statistics, 2008. CA Cancer J Clin, 2008. 58(2): p. 71-96.

    2. Johns, N., N.A. Stephens, and K.C. Fearon, Muscle wasting in cancer. Int J Biochem Cell Biol, 2013. 45(10): p. 2215-29.

    3. Klassen, O., et al., Muscle strength in breast cancer patients receiving different treatment regimes. Journal of Cachexia, Sarcopenia and Muscle, 2017. 8(2): p. 305-316.

    4. Villasenor, A., et al., Prevalence and prognostic effect of sarcopenia in breast cancer survivors: the HEAL Study. J Cancer Surviv, 2012. 6(4): p. 398-406.

    5. Perry, S., T.L. Kowalski, and C.H. Chang, Quality of life assessment in women with breast cancer: benefits, acceptability and utilization. Health Qual Life Outcomes, 2007. 5: p. 24.

    6. Fantozzi, A. and G. Christofori, Mouse models of breast cancer metastasis. Breast Cancer Res, 2006. 8(4): p. 212.

  • 47.
    Malgoyre, A
    et al.
    Institut de Recherche Biomdicale de Armes, La Tronche, France.
    Sanchez, H
    Institut de Recherche Biomdicale de Armes, La Tronche, France.
    Tonini, J
    Institut de Recherche Biomdicale de Armes, La Tronche, France.
    Serrurier, B
    Institut de Recherche Biomdicale de Armes, La Tronche, France.
    Prola, A
    Institut de Recherche Biomdicale de Armes, La Tronche, France.
    Chaillou, Thomas
    Institut de Recherche Biomdicale de Armes, La Tronche, France.
    Simler, N
    Institut de Recherche Biomdicale de Armes, La Tronche, France.
    Bigard, X
    Institut de Recherche Biomdicale de Armes, La Tronche, France.
    Aerobic performance improvment and mitochondrial adaptations after endurance training in hypoxia2011In: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 202, no Suppl. 685Article in journal (Refereed)
    Abstract [en]

    Aim: The aim of the present study was to examine the effects of hypoxic endurance training on both aerobic performance and mitochondrial changes within plantaris muscle, independently of hematopoietic modifications.

    Methods: Four groups of female rats were constituted either sedentary (S) or trained (T), in either hypoxia (H) or normoxia (N). H conditions corresponded to 14% O2 and the training program to 5 running sessions/week for 5 weeks. Duration and intensity reached progressively 75Õ up to 80% of individual maximal aerobic running velocity (MAV) in either H or N. Performances of each rat were analysed through MAV values and time to exhaustion at 65% MAV (T65). Mitochondrial oxidative capacities (Vmax) for pyruvate (pyr), palmitoyl-carnitine (PC) and palmitoyl-CoA (PCoA) were measured in plantaris skinned fibers. Citrate synthase (CS) and HAD activities were also measured.

    Results: MAV increased in both TN and TH rats (respectively +52%, +39%, P<0.001) without difference between H and N, whereas hypoxia specifically increased T65 (+ 39%, P<0.05) independently of training effect. The training-induced increase in CS activity (P<0.001) was more marked in TN than in TH group (+39% vs +26%, P<0.001) whereas HAD activity rose similarly in TN and TH (respectively +83%, +64%, P<0.05). Physical training increased Vmaxpyr only in N rats (+30%, P<0.001), while VmaxPCoA decreased in hypoxia (P<0.05) without change in VmaxPC. This suggests that LCFA transport by CPT-1 was limiting in hypoxia. As expected, training improved creatine kinase efficiency in N rats (+80%, P<0.005), but no change was shown in H rats.

    Conclusion: Regarding the modest changes in mitochondrial function, it is likely that other factors contribute to explain the improvement of physical performance after an endurance training in hypoxia.

  • 48.
    Pugnière, P
    et al.
    Genomic Core Facility, IRBA La Tronche, La Tronche, France.
    Banzet, S
    Operational Environments, IRBA La Tronche, La Tronche, France.
    Chaillou, Thomas
    Operational Environments, IRBA La Tronche, La Tronche, France.
    Mouret, C
    Genomic Core Facility, IRBA La Tronche, La Tronche, France.
    Peinnequin, A
    Genomic Core Facility, IRBA La Tronche, La Tronche, France.
    Pitfalls of reverse transcription quantitative polymerase chain reaction standardization: Volume-related inhibitors of reverse transcription2011In: Analytical Biochemistry, ISSN 0003-2697, E-ISSN 1096-0309, Vol. 415, no 2, p. 151-157Article in journal (Refereed)
    Abstract [en]

    A large part of the reliability of reverse transcription quantitative polymerase chain reaction (RT-qPCR) data depends on technical variations. Such variations are mainly attributable to the reverse transcription step. Standardization is a key factor in decreasing the intersample variability. However, an ideal standardization is not always possible, and compromises must be found. Due to technical requirements, the current consensus is that a constant amount of total RNA should be used for the RT step (CA-RT). Because RNA isolation yields are variable, such a practice requires the use of variable volumes of nucleic acid extracts in RT reaction. We demonstrate that some RNA extracts contain both exogenous and endogenous inhibitors. These inhibitors induce a decrease in RT efficiency that significantly impairs the reliability of RT-qPCR data. Conversely, these inhibitors have a slight effect on the qPCR step. To overcome such drawbacks, we proposed to carry out the RT reaction with a constant volume of RNA extract by preserving a constant RNA amount through the supplementation of yeast transfer RNA (CV-RT). We show that CV-RT, compared with the usual CA-RT, allows us to decrease the RT-qPCR variability induced by intersample differences. Such a decrease is a prerequisite for the reliability of messenger RNA quantification.

  • 49. Pugnière, P.
    et al.
    Banzet, S.
    Chaillou, Thomas
    University of Kentucky, Lexington KY, United States .
    Mouret, C
    Peinnequin, A.
    Volume-related inhibitors standardization for reverse transcription quantitative polymerase chain reaction experiments2012Conference paper (Refereed)
    Abstract [en]

    A large part of the reliability of reverse transcription quantitative polymerase chain reaction (RT-qPCR) data depends on technical variations. Such variations are mainly attributable to the reverse transcription step. Standardization is a key factor in decreasing the intersample variability. However, an ideal standardization is not always possible, and compromises must be found. Due to technical requirements, the current consensus is that a constant amount of total RNA should be used for the RT step (CA-RT). Because RNA isolation yields are variable, such a practice requires the use of variable volumes of nucleic acid extracts in RT reaction. We demonstrate that some RNA extracts contain both exogenous and endogenous inhibitors. These inhibitors induce a decreased RT efficiency that significantly impairs the reliability of RT-qPCR data. Conversely, these inhibitors have slight effects on the qPCR step. To overcome such drawbacks, we proposed to carry out the RT reaction with a constant volume of RNA extract by preserving a constant RNA amount through the supplementation of yeast transfer RNA (CV-RT). We show that CV-RT, compared with the usual CA-RT, allows us to decrease the RT-qPCR variability induced by intersample differences. Such a decrease is a prerequisite for the reliability of messenger RNA quantification.

  • 50.
    Ramos, Catarina
    et al.
    School of Health Sciences, Örebro University, Örebro, Sweden.
    Cheng, Arthur J.
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden; Muscle Health Research Centre, School of Kinesiology and Health Sciences, Faculty of Health, York University, Toronto, Canada.
    Kamandulis, Sigitas
    Sports Science and Innovation Institute, Lithuanian Sports University, Kaunas, Lithuania.
    Subocius, Andrejus
    Sports Science and Innovation Institute, Lithuanian Sports University, Kaunas, Lithuania; Department of Surgery, Kaunas Clinical Hospital, Kaunas, Lithuania; Clinic of Surgery, Republican Hospital of Kaunas, Kaunas, Lithuania.
    Brazaitis, Marius
    Sports Science and Innovation Institute, Lithuanian Sports University, Kaunas, Lithuania.
    Venckunas, Tomas
    Sports Science and Innovation Institute, Lithuanian Sports University, Kaunas, Lithuania.
    Chaillou, Thomas
    Örebro University, School of Health Sciences.
    Carbohydrate restriction following strenuous glycogen-depleting exercise does not potentiate the acute molecular response associated with mitochondrial biogenesis in human skeletal muscle2021In: European Journal of Applied Physiology, ISSN 1439-6319, E-ISSN 1439-6327, Vol. 121, no 4, p. 1219-1232Article in journal (Refereed)
    Abstract [en]

    PURPOSE: Carbohydrate (CHO) restriction could be a potent metabolic regulator of endurance exercise-induced muscle adaptations. Here, we determined whether post-exercise CHO restriction following strenuous exercise combining continuous cycling exercise (CCE) and sprint interval exercise could affect the gene expression related to mitochondrial biogenesis and oxidative metabolism in human skeletal muscle.

    METHODS: In a randomized cross-over design, 8 recreationally active males performed two cycling exercise sessions separated by 4 weeks. Each session consisted of 60-min CCE and six 30-s all-out sprints, which was followed by ingestion of either a CHO or placebo beverage in the post-exercise recovery period. Muscle glycogen concentration and the mRNA levels of several genes related to mitochondrial biogenesis and oxidative metabolism were determined before, immediately after, and at 3 h after exercise.

    RESULTS: Compared to pre-exercise, strenuous cycling led to a severe muscle glycogen depletion (> 90%) and induced a large increase in PGC1A and PDK4 mRNA levels (~ 20-fold and ~ 10-fold, respectively) during the acute recovery period in both trials. The abundance of the other transcripts was not changed or was only moderately increased during this period. CHO restriction during the 3-h post-exercise period blunted muscle glycogen resynthesis but did not increase the mRNA levels of genes associated with muscle adaptation to endurance exercise, as compared with abundant post-exercise CHO consumption.

    CONCLUSION: CHO restriction after a glycogen-depleting and metabolically-demanding cycling session is not effective for increasing the acute mRNA levels of genes involved in mitochondrial biogenesis and oxidative metabolism in human skeletal muscle.

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