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GIANNESINI Benoit

MD PhD

mail@univ-amu.fr
tel : +33 4 91 38 ** **
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Current Research Interest and projects

Publications

2016

Journal Article

  • BéCHIR N., PECCHI E., VILMEN C., LE FUR Y., AMTHOR H., BERNARD M., BENDAHAN D., GIANNESINI B. “ActRIIB blockade increases force-generating capacity and preserves energy supply in exercising mdx mouse muscle in vivo.”. FASEB journal: official publication of the Federation of American Societies for Experimental Biology [En ligne]. 2016. Vol. 30, n°10, p. 3551-3562. Disponible sur : < http://dx.doi.org/10.1096/fj.201600271RR > (consulté le no date)
    Résumé : Postnatal blockade of the activin type IIB receptor (ActRIIB) represents a promising therapeutic strategy for counteracting dystrophic muscle wasting. However, its impact on muscle function and bioenergetics remains poorly documented in physiologic conditions. We have investigated totally noninvasively the effect of 8-wk administration of either soluble ActRIIB signaling inhibitor (sActRIIB-Fc) or vehicle PBS (control) on gastrocnemius muscle force-generating capacity, energy metabolism, and anatomy in dystrophic mdx mice using magnetic resonance (MR) imaging and dynamic [(31)P]-MR spectroscopy ([(31)P]-MRS) in vivo ActRIIB inhibition increased muscle volume (+33%) without changing fiber-type distribution, and increased basal animal oxygen consumption (+22%) and energy expenditure (+23%). During an in vivo standardized fatiguing exercise, maximum and total absolute contractile forces were larger (+40 and 24%, respectively) in sActRIIB-Fc treated animals, whereas specific force-generating capacity and fatigue resistance remained unaffected. Furthermore, sActRIIB-Fc administration did not alter metabolic fluxes, ATP homeostasis, or contractile efficiency during the fatiguing bout of exercise, although it dramatically reduced the intrinsic mitochondrial capacity for producing ATP. Overall, sActRIIB-Fc treatment increased muscle mass and strength without altering the fundamental weakness characteristic of dystrophic mdx muscle. These data support the clinical interest of ActRIIB blockade for reversing dystrophic muscle wasting.-Béchir, N., Pecchi, E., Vilmen, C., Le Fur, Y., Amthor, H., Bernard, M., Bendahan, D., Giannesini, B. ActRIIB blockade increases force-generating capacity and preserves energy supply in exercising mdx mouse muscle in vivo.
    Mots-clés : crmbm, Duchenne muscular dystrophy, Muscle Fatigue, myostatin inhibition, skeletal muscle hypertrophy.

  • GHISS M., GIANNESINI B., TROPIANO P., TOURKI Z., BOIRON O. “Quantitative MRI water content mapping of porcine intervertebral disc during uniaxial compression.”. Computer Methods in Biomechanics and Biomedical Engineering [En ligne]. 2016. Vol. 19, n°10, p. 1079-1088. Disponible sur : < http://dx.doi.org/10.1080/10255842.2015.1101072 > (consulté le no date)
    Résumé : Background: Intervertebral disc (IVD) diseases are major public health problem in industrialized countries where they affect a large proportion of the population. In particular, IVD degeneration is considered to be one of the leading causes of pain consultation and sick leave. The aim of this study was to develop a new method for assessing the functionality of IVD in order to diagnose IVD degeneration. Methods: For this purpose, we have designed a specific device that enables to mechanically load porcine IVD ex vivo in the 4.7-Tesla horizontal superconducting magnet of a magnetic resonance (MR) scanner. Proton density weighted imaging (rho(H)-MRI) of the samples was acquired. Findings: The post-processing on MR images allowed (1) to reconstruct the 3D deformation under a known mechanical load and (2) to infer the IVD porosity assuming an incompressible poroelastic model. Interpretation: This study demonstrates the ability to follow the change in morphology and hydration of an IVD using MR measurements, thereby providing valued information for a better understanding of IVD function.
    Mots-clés : bovine articular-cartilage, cell viability, creep response analysis, finite-element-analysis, fluid content, IVD, nucleus pulposus, poroelasticity, porosity, rho(H)-MRI, solute transport, swelling pressure, unconfined compression, vertebral bodies, ρH-MRI.

2015

Journal Article


  • ABDESSELAM I., PEPINO P., TROALEN T., MACIA M., ANCEL P., MASI B., FOURNY N., GABORIT B., GIANNESINI B., KOBER F., DUTOUR A., BERNARD M. “Time course of cardiometabolic alterations in a high fat high sucrose diet mice model and improvement after GLP-1 analog treatment using multimodal cardiovascular magnetic resonance.”. Journal of Cardiovascular Magnetic Resonance [En ligne]. 06 November 2015. Vol. 17, n°1, p. 95. Disponible sur : < http://dx.doi.org/10.1186/s12968-015-0198-x >
    Résumé : Cardiovascular complications of obesity and diabetes are major health problems. Assessing their development, their link with ectopic fat deposition and their flexibility with therapeutic intervention is essential. The aim of this study was to longitudinally investigate cardiac alterations and ectopic fat accumulation associated with diet-induced obesity using multimodal cardiovascular magnetic resonance (CMR) in mice. The second objective was to monitor cardiac response to exendin-4 (GLP-1 receptor agonist).
    Mots-clés : Cardiovascular magnetic resonance, crmbm, Diabetes, DIO mice model, Longitudinal study, Obesity, Proton-magnetic resonance spectroscopy.

  • MACIA M., PECCHI E., VILMEN C., DESROIS M., LAN C., PORTHA B., BERNARD M., BENDAHAN D., GIANNESINI B. “Insulin Resistance Is Not Associated with an Impaired Mitochondrial Function in Contracting Gastrocnemius Muscle of Goto-Kakizaki Diabetic Rats In Vivo.”. PloS One [En ligne]. 2015. Vol. 10, n°6, p. e0129579. Disponible sur : < http://dx.doi.org/10.1371/journal.pone.0129579 > (consulté le no date)
    Résumé : Insulin resistance, altered lipid metabolism and mitochondrial dysfunction in skeletal muscle would play a major role in type 2 diabetes mellitus (T2DM) development, but the causal relationships between these events remain conflicting. To clarify this issue, gastrocnemius muscle function and energetics were investigated throughout a multidisciplinary approach combining in vivo and in vitro measurements in Goto-Kakizaki (GK) rats, a non-obese T2DM model developing peripheral insulin resistant without abnormal level of plasma non-esterified fatty acids (NEFA). Wistar rats were used as controls. Mechanical performance and energy metabolism were assessed strictly non-invasively using magnetic resonance (MR) imaging and 31-phosphorus MR spectroscopy (31P-MRS). Compared with control group, plasma insulin and glucose were respectively lower and higher in GK rats, but plasma NEFA level was normal. In resting GK muscle, phosphocreatine content was reduced whereas glucose content and intracellular pH were both higher. However, there were not differences between both groups for basal oxidative ATP synthesis rate, citrate synthase activity, and intramyocellular contents for lipids, glycogen, ATP and ADP (an important in vivo mitochondrial regulator). During a standardized fatiguing protocol (6 min of maximal repeated isometric contractions electrically induced at a frequency of 1.7 Hz), mechanical performance and glycolytic ATP production rate were reduced in diabetic animals whereas oxidative ATP production rate, maximal mitochondrial capacity and ATP cost of contraction were not changed. These findings provide in vivo evidence that insulin resistance is not caused by an impairment of mitochondrial function in this diabetic model.
    Mots-clés : crmbm.

  • YASHIRO K., TONSON A., PECCHI É., VILMEN C., LE FUR Y., BERNARD M., BENDAHAN D., GIANNESINI B. “Capsiate Supplementation Reduces Oxidative Cost of Contraction in Exercising Mouse Skeletal Muscle In Vivo.”. PloS One [En ligne]. 2015. Vol. 10, n°6, p. e0128016. Disponible sur : < http://dx.doi.org/10.1371/journal.pone.0128016 > (consulté le no date)
    Résumé : Chronic administration of capsiate is known to accelerate whole-body basal energy metabolism, but the consequences in exercising skeletal muscle remain very poorly documented. In order to clarify this issue, the effect of 2-week daily administration of either vehicle (control) or purified capsiate (at 10- or 100-mg/kg body weight) on skeletal muscle function and energetics were investigated throughout a multidisciplinary approach combining in vivo and in vitro measurements in mice. Mechanical performance and energy metabolism were assessed strictly non-invasively in contracting gastrocnemius muscle using magnetic resonance (MR) imaging and 31-phosphorus MR spectroscopy (31P-MRS). Regardless of the dose, capsiate treatments markedly disturbed basal bioenergetics in vivo including intracellular pH alkalosis and decreased phosphocreatine content. Besides, capsiate administration did affect neither mitochondrial uncoupling protein-3 gene expression nor both basal and maximal oxygen consumption in isolated saponin-permeabilized fibers, but decreased by about twofold the Km of mitochondrial respiration for ADP. During a standardized in vivo fatiguing protocol (6-min of repeated maximal isometric contractions electrically induced at a frequency of 1.7 Hz), both capsiate treatments reduced oxidative cost of contraction by 30-40%, whereas force-generating capacity and fatigability were not changed. Moreover, the rate of phosphocreatine resynthesis during the post-electrostimulation recovery period remained unaffected by capsiate. Both capsiate treatments further promoted muscle mass gain, and the higher dose also reduced body weight gain and abdominal fat content. These findings demonstrate that, in addition to its anti-obesity effect, capsiate supplementation improves oxidative metabolism in exercising muscle, which strengthen this compound as a natural compound for improving health.
    Mots-clés : crmbm.

2014

Journal Article

  • KAZUYA Y., TONSON A., PECCHI E., DALMASSO C., VILMEN C., FUR Y. L., BERNARD M., BENDAHAN D., GIANNESINI B. “A single intake of capsiate improves mechanical performance and bioenergetics efficiency in contracting mouse skeletal muscle.”. American Journal of Physiology. Endocrinology and Metabolism [En ligne]. 2014. Vol. 306, n°10, p. E1110-1119. Disponible sur : < http://dx.doi.org/10.1152/ajpendo.00520.2013 > (consulté le no date)
    Résumé : Capsiate is known to increase whole body oxygen consumption possibly via the activation of uncoupling processes, but its effect at the skeletal muscle level remains poorly documented and conflicting. To clarify this issue, gastrocnemius muscle function and energetics were investigated in mice 2 h after a single intake of either vehicle (control) or purified capsiate (at 10 or 100 mg/kg body wt) through a multidisciplinary approach combining in vivo and in vitro measurements. Mechanical performance and energy pathway fluxes were assessed strictly noninvasively during a standardized electrostimulation-induced exercise, using an original device implementing 31-phosphorus magnetic resonance spectroscopy, and mitochondrial respiration was evaluated in isolated saponin-permeabilized fibers. Compared with control, both capsiate doses produced quantitatively similar effects at the energy metabolism level, including an about twofold decrease of the mitochondrial respiration sensitivity for ADP. Interestingly, they did not alter either oxidative phosphorylation or uncoupling protein 3 gene expression at rest. During 6 min of maximal repeated isometric contractions, both doses reduced the amount of ATP produced from glycolysis and oxidative phosphorylation but increased the relative contribution of oxidative phosphorylation to total energy turnover (+28 and +21% in the 10- and 100-mg groups, respectively). ATP cost of twitch force generation was further reduced in the 10- (-35%) and 100-mg (-45%) groups. Besides, the highest capsiate dose also increased the twitch force-generating capacity. These data present capsiate as a helpful candidate to enhance both muscle performance and oxidative phosphorylation during exercise, which could constitute a nutritional approach for improving health and preventing obesity and associated metabolic disorders.
    Mots-clés : Animals, Biomechanical Phenomena, Capsaicin, Cells, Cultured, crmbm, Electric Stimulation, Energy Metabolism, Male, Mice, Mice, Inbred C57BL, Muscle Contraction, Muscle, Skeletal, Physical Conditioning, Animal.
    Attachment Full Text PDF 307.6 kb (source)

  • MARCOTORCHINO J., TOURNIAIRE F., ASTIER J., KARKENI E., CANAULT M., AMIOT M. - J., BENDAHAN D., BERNARD M., MARTIN J. - C., GIANNESINI B., LANDRIER J. - F. “Vitamin D protects against diet-induced obesity by enhancing fatty acid oxidation.”. The Journal of Nutritional Biochemistry [En ligne]. 2014. Vol. 25, n°10, p. 1077-1083. Disponible sur : < http://dx.doi.org/10.1016/j.jnutbio.2014.05.010 > (consulté le no date)
    Résumé : Prospective studies reported an inverse correlation between 25-hydroxyvitamin D [25(OH)D] plasma levels and prevalence of obesity and type 2 diabetes. In addition, 25(OH)D status may be a determinant of obesity onset. However, the causality between these observations is not yet established. We studied the preventive effect of vitamin D3 (VD3) supplementation (15,000IU/kg of food for 10weeks) on onset of obesity in a diet-induced obesity mouse model. We showed that the VD3 supplementation limited weight gain induced by high-fat diet, which paralleled with an improvement of glucose homeostasis. The limitation of weight gain could further be explained by an increased lipid oxidation, possibly due to an up-regulation of genes involved in fatty acid oxidation and mitochondrial metabolism, leading to increased energy expenditure. Altogether, these data show that VD3 regulates energy expenditure and suggest that VD3 supplementation may represent a strategy of preventive nutrition to fight the onset of obesity and associated metabolic disorders.

  • RELIZANI K., MOUISEL E., GIANNESINI B., HOURDé C., PATEL K., MORALES GONZALEZ S., JüLICH K., VIGNAUD A., PIéTRI-ROUXEL F., FORTIN D., GARCIA L., BLOT S., RITVOS O., BENDAHAN D., FERRY A., VENTURA-CLAPIER R., SCHUELKE M., AMTHOR H. “Blockade of ActRIIB signaling triggers muscle fatigability and metabolic myopathy.”. Molecular Therapy: The Journal of the American Society of Gene Therapy [En ligne]. 2014. Vol. 22, n°8, p. 1423-1433. Disponible sur : < http://dx.doi.org/10.1038/mt.2014.90 > (consulté le no date)
    Résumé : Myostatin regulates skeletal muscle size via the activin receptor IIB (ActRIIB). However, its effect on muscle energy metabolism and energy-dependent muscle function remains largely unexplored. This question needs to be solved urgently since various therapies for neuromuscular diseases based on blockade of ActRIIB signaling are being developed. Here, we show in mice, that 4-month pharmacological abrogation of ActRIIB signaling by treatment with soluble ActRIIB-Fc triggers extreme muscle fatigability. This is associated with elevated serum lactate levels and a severe metabolic myopathy in the mdx mouse, an animal model of Duchenne muscular dystrophy. Blockade of ActRIIB signaling downregulates porin, a crucial ADP/ATP shuttle between cytosol and mitochondrial matrix leading to a consecutive deficiency of oxidative phosphorylation as measured by in vivo Phosphorus Magnetic Resonance Spectroscopy ((31)P-MRS). Further, ActRIIB blockade reduces muscle capillarization, which further compounds the metabolic stress. We show that ActRIIB regulates key determinants of muscle metabolism, such as Pparβ, Pgc1α, and Pdk4 thereby optimizing different components of muscle energy metabolism. In conclusion, ActRIIB signaling endows skeletal muscle with high oxidative capacity and low fatigability. The severe metabolic side effects following ActRIIB blockade caution against deploying this strategy, at least in isolation, for treatment of neuromuscular disorders.

2013

Journal Article

  • GIANNESINI B., VILMEN C., AMTHOR H., BERNARD M., BENDAHAN D. “Lack of myostatin impairs mechanical performance and ATP cost of contraction in exercising mouse gastrocnemius muscle in vivo.”. American journal of physiology. Endocrinology and metabolism [En ligne]. 2013. Vol. 305, n°1, p. E33-40. Disponible sur : < http://dx.doi.org/10.1152/ajpendo.00651.2012 > (consulté le no date)
    Résumé : Although it is well established that the lack of myostatin (Mstn) promotes skeletal muscle hypertrophy, the corresponding changes regarding force generation have been studied mainly in vitro and remain conflicting. Furthermore, the metabolic underpinnings of these changes are very poorly documented. To clarify this issue, we have investigated strictly noninvasively in vivo the impact of the lack of Mstn on gastrocnemius muscle function and energetics in Mstn-targeted knockout (Mstn-/-) mice using ¹H-magnetic resonance (MR) imaging and ³¹P-MR spectroscopy during maximal repeated isometric contractions induced by transcutaneous electrostimulation. In Mstn-/- animals, although body weight, gastrocnemius muscle volume, and absolute force were larger (+38, +118, and +34%, respectively) compared with wild-type (Mstn+/+) mice, specific force (calculated from MR imaging measurements) was significantly lower (-36%), and resistance to fatigue was decreased. Besides, Mstn deficiency did not affect phosphorylated compound concentrations and intracellular pH at rest but caused a large increase in ATP cost of contraction (up to +206% compared with Mstn+/+) throughout the stimulation period. Further, Mstn deficiency limits the shift toward oxidative metabolism during muscle activity despite the fact that oxidative ATP synthesis capacity was not altered. Our data demonstrate in vivo that the absence of Mstn impairs both mechanical performance and energy cost of contraction in hypertrophic muscle. These findings must be kept in mind when considering Mstn as a potential therapeutic target for increasing muscle mass in patients suffering from muscle-wasting disorders.
    Mots-clés : Adenosine Triphosphate, Animals, Biomechanics, crmbm, Electric Stimulation, Energy Metabolism, Female, Mice, Mice, Inbred C57BL, Mice, Knockout, Muscle Contraction, Muscle, Skeletal, Muscular Atrophy, Myostatin, Physical Conditioning, Animal.

  • GINESTE C., DE WINTER J. M., KOHL C., WITT C. C., GIANNESINI B., BROHM K., LE FUR Y., GRETZ N., VILMEN C., PECCHI E., JUBEAU M., COZZONE P. J., STIENEN G. J. M., GRANZIER H., LABEIT S., OTTENHEIJM C. A. C., BENDAHAN D., GONDIN J. “In vivo and in vitro investigations of heterozygous nebulin knock-out mice disclose a mild skeletal muscle phenotype.”. Neuromuscular disorders: NMD [En ligne]. 2013. Vol. 23, n°4, p. 357-369. Disponible sur : < http://dx.doi.org/10.1016/j.nmd.2012.12.011 > (consulté le no date)
    Résumé : Nemaline myopathy is the most common congenital skeletal muscle disease, and mutations in the nebulin gene account for 50% of all cases. Recent studies suggest that the disease severity might be related to the nebulin expression levels. Considering that mutations in the nebulin gene are typically recessive, one would expect that a single functional nebulin allele would maintain nebulin protein expression which would result in preserved skeletal muscle function. We investigated skeletal muscle function of heterozygous nebulin knock-out (i.e., nebulin(+/-)) mice using a multidisciplinary approach including protein and gene expression analysis and combined in vivo and in vitro force measurements. Skeletal muscle anatomy and energy metabolism were studied strictly non-invasively using magnetic resonance imaging and 31P-magnetic resonance spectroscopy. Maximal force production was reduced by around 16% in isolated muscle of nebulin(+/-) mice while in vivo force generating capacity was preserved. Muscle weakness was associated with a shift toward a slower proteomic phenotype, but was not related to nebulin protein deficiency or to an impaired energy metabolism. Further studies would be warranted in order to determine the mechanisms leading to a mild skeletal muscle phenotype resulting from the expression of a single nebulin allele.
    Mots-clés : Animals, crmbm, Disease Models, Animal, Gene Expression, Heterozygote, Magnetic Resonance Imaging, Magnetic Resonance Spectroscopy, Male, Mice, Mice, Knockout, Muscle Proteins, Muscle Strength, Muscle Weakness, Muscle, Skeletal, Mutation, Myopathies, Nemaline, Phenotype, Severity of Illness Index.
    Note Note
    <p>The following values have no corresponding Zotero field:<br />Author Address: Aix-Marseille Universite, CRMBM, 13005 Marseille, France; CNRS, Centre de Resonance Magnetique Biologique et Medicale (CRMBM), 13005 Marseille, France.<br />C2 - Muscle <br />ET - 2013/02/05<br /></p>
    Note Note
    <p>Gineste, C<br />De Winter, J M<br />Kohl, C<br />Witt, C C<br />Giannesini, B<br />Brohm, K<br />Le Fur, Y<br />Gretz, N<br />Vilmen, C<br />Pecchi, E<br />Jubeau, M<br />Cozzone, P J<br />Stienen, G J M<br />Granzier, H<br />Labeit, S<br />Ottenheijm, C A C<br />Bendahan, D<br />Gondin, J<br />England<br />Neuromuscular disorders : NMD<br />Neuromuscul Disord. 2013 Apr;23(4):357-69. doi: 10.1016/j.nmd.2012.12.011. Epub 2013 Feb 1.</p>

2011

Journal Article

  • GIANNESINI B., LE FUR Y., COZZONE P. J., VERLEYE M., LE GUERN M. - E., BENDAHAN D. “Citrulline malate supplementation increases muscle efficiency in rat skeletal muscle.”. European journal of pharmacology [En ligne]. 2011. Vol. 667, n°1-3, p. 100-104. Disponible sur : < http://dx.doi.org/10.1016/j.ejphar.2011.05.068 > (consulté le no date)
    Résumé : Citrulline malate (CM; CAS 54940-97-5, Stimol®) is known to limit the deleterious effect of asthenic state on muscle function, but its effect under healthy condition remains poorly documented. The aim of this longitudinal double-blind study was to investigate the effect of oral ingestion of CM on muscle mechanical performance and bioenergetics in normal rat. Gastrocnemius muscle function was investigated strictly non-invasively using nuclear magnetic resonance techniques. A standardized rest-stimulation- (5.7 min of repeated isometric contractions electrically induced by transcutaneous stimulation at a frequency of 3.3 Hz) recovery-protocol was performed twice, i.e., before (t(0)-24 h) and after (t(0)+48 h) CM (3 g/kg/day) or vehicle treatment. CM supplementation did not affect PCr/ATP ratio, [PCr], [Pi], [ATP] and intracellular pH at rest. During the stimulation period, it lead to a 23% enhancement of specific force production that was associated to significant decrease in both PCr (28%) and oxidative (32%) costs of contraction, but had no effect on the time-courses of phosphorylated compounds and intracellular pH. Furthermore, both the rate of PCr resynthesis during the post-stimulation period (VPCr(rec)) and the oxidative ATP synthesis capacity (Q(max)) remained unaffected by CM treatment. These data demonstrate that CM supplementation under healthy condition has an ergogenic effect associated to an improvement of muscular contraction efficiency.
    Mots-clés : Administration, Oral, Animals, Biomechanics, Citrulline, crmbm, Electric Stimulation, Energy Metabolism, Malates, Male, Muscle, Skeletal, Oxidation-Reduction, Rats, Rats, Wistar.

  • GONDIN J., GIANNESINI B., VILMEN C., LE FUR Y., COZZONE P. J., BENDAHAN D. “Effects of a single bout of isometric neuromuscular electrical stimulation on rat gastrocnemius muscle: a combined functional, biochemical and MRI investigation.”. Journal of electromyography and kinesiology: official journal of the International Society of Electrophysiological Kinesiology [En ligne]. 2011. Vol. 21, n°3, p. 525-532. Disponible sur : < http://dx.doi.org/10.1016/j.jelekin.2011.01.006 > (consulté le no date)
    Résumé : While muscle damage resulting from electrically-induced muscle isometric contractions has been reported in humans, animal studies have failed to illustrate similar deleterious effects and it remains to be determined whether these conflicting results are related to differences regarding experimental procedures or to species. We have investigated in vivo, in rat gastrocnemius muscles, using experimental conditions as close as possible to those used in humans (i.e., muscle length, number of contractions, stimulated muscle), the effects of a single bout of neuromuscular electrical stimulation (NMES). Maximal tetanic force was measured before, immediately after and 1h and 1, 2, 3, 7 and 14 days after NMES. Magnetic resonance imaging measurements, including volume of gastrocnemius muscles and proton transverse relaxation time (T(2)) were performed at baseline and 3, 7, and 14 days after the NMES session. Control animals did not perform any exercise and measurements were recorded at the same time points. For both groups, blood creatine kinase (CK) activity was measured within the first 3 days that followed the initial evaluation. Maximal tetanic force decreased immediately after NMES whereas measurements performed 1h and the days afterwards were similar to the baseline values. CK activity, muscle volume and T(2) values were similar throughout the experimental protocol between the two groups. Under carefully controlled experimental conditions, isometric NMES per se did not induce muscle damage in rat gastrocnemius muscles on the contrary to what has been repeatedly reported in humans. Further experiments would then be warranted in order to clearly delineate these differences and to better understand the physiological events associated with muscle damage resulting from NMES-induced isometric contractions.
    Mots-clés : Animals, crmbm, Electric Stimulation, Isometric Contraction, Magnetic Resonance Imaging, Male, Muscle Fatigue, Muscle, Skeletal, Physical Endurance, Rats, Rats, Wistar.

2010

Journal Article

  • GIANNESINI B., VILMEN C., LE FUR Y., DALMASSO C., COZZONE P. J., BENDAHAN D. “A strictly noninvasive MR setup dedicated to longitudinal studies of mechanical performance, bioenergetics, anatomy, and muscle recruitment in contracting mouse skeletal muscle.”. Magnetic resonance in medicine: official journal of the Society of Magnetic Resonance in Medicine / Society of Magnetic Resonance in Medicine [En ligne]. 2010. Vol. 64, n°1, p. 262-270. Disponible sur : < http://dx.doi.org/10.1002/mrm.22386 > (consulté le no date)
    Résumé : MR techniques have proven their ability to investigate skeletal muscle function in situ. Their benefit in terms of noninvasiveness is, however, lost in animal research, given that muscle stimulation and force output measurements are usually achieved using invasive surgical procedures, thereby excluding repeated investigations in the same animal. This study describes a new setup allowing strictly noninvasive investigations of mouse gastrocnemius muscle function using (1)H-MRI and (31)P-MR spectroscopy. Its originality is to integrate noninvasive systems for inducing muscle contraction through transcutaneous stimulation and for measuring mechanical performance with a dedicated ergometer. In order to test the setup, muscle function was investigated using a fatiguing stimulation protocol (6 min of repeated isometric contractions at 1.7 Hz). T(2)-weighted imaging demonstrated that transcutaneous stimulation mainly activated the gastrocnemius. Moreover, investigations repeated twice with a 7-day interval between bouts did show a high reproducibility in measurements with regard to changes in isometric force and energy metabolism. In conclusion, this setup enables us for the first time to access mechanical performance, energy metabolism, anatomy, and physiology strictly noninvasively in contracting mouse skeletal muscle. The possibility for implementing longitudinal studies opens up new perspectives in many research areas, including ageing, pharmaceutical research, and gene and cell therapy.
    Mots-clés : Animals, Energy Metabolism, Hindlimb, Longitudinal Studies, Magnetic Resonance Spectroscopy, Mice, Mice, Inbred C57BL, Muscle Contraction, Muscle, Skeletal, Reproducibility of Results.

  • GONDIN J., GIANNESINI B., VILMEN C., DALMASSO C., LE FUR Y., COZZONE P. J., BENDAHAN D. “Effects of stimulation frequency and pulse duration on fatigue and metabolic cost during a single bout of neuromuscular electrical stimulation.”. Muscle & nerve [En ligne]. 2010. Vol. 41, n°5, p. 667-678. Disponible sur : < http://dx.doi.org/10.1002/mus.21572 > (consulté le no date)
    Résumé : We have investigated the effects of stimulation frequency and pulse duration on fatigue and energy metabolism in rat gastrocnemius muscle during a single bout of neuromuscular electrical stimulation (NMES). Electrical pulses were delivered at 100 Hz (1-ms pulse duration) and 20 Hz (5-ms pulse duration) for the high (HF) and low (LF) frequency protocols, respectively. As a standardization procedure, the averaged stimulation intensity, the averaged total charge, the initial peak torque, the duty cycle, the contraction duration and the torque-time integral were similar in both protocols. Fatigue was assessed using two testing trains delivered at a frequency of 100 Hz and 20 Hz before and after each protocol. Metabolic changes were investigated in vivo using 31P-magnetic resonance spectroscopy (31P-MRS) and in vitro in freeze-clamped muscles. Both LF and HF NMES protocols induced the same decrease in testing trains and metabolic changes. We conclude that, under carefully controlled and comparable conditions, the use of low stimulation frequency and long pulse duration do not minimize the occurrence of muscle fatigue or affect the corresponding stimulation-induced metabolic changes so that this combination of stimulation parameters would not be adequate in the context of rehabilitation.
    Mots-clés : Adenosine Triphosphate, Animals, crmbm, Electric Stimulation, Electric Stimulation Therapy, Energy Metabolism, Exercise Tolerance, Magnetic Resonance Spectroscopy, Male, Motor Neurons, Muscle Contraction, Muscle Fatigue, Muscle Fibers, Skeletal, Muscle Weakness, Muscle, Skeletal, Neuromuscular Junction, Peripheral Nerves, Rats, Rats, Wistar, Time Factors.

2009

Journal Article

  • FARAUT B., GIANNESINI B., MATARAZZO V., LE FUR Y., ROUGON G., COZZONE P. J., BENDAHAN D. “Capsiate administration results in an uncoupling protein-3 downregulation, an enhanced muscle oxidative capacity and a decreased abdominal fat content in vivo.”. International journal of obesity (2005) [En ligne]. 2009. Vol. 33, n°12, p. 1348-1355. Disponible sur : < http://dx.doi.org/10.1038/ijo.2009.182 > (consulté le no date)
    Résumé : OBJECTIVES: The involvement of skeletal muscle mitochondrial uncoupling protein-3 (UCP3) in the control of energy expenditure in skeletal muscle and at the whole-body level is still a matter of debate. We previously reported that UCP3 downregulation is linked to an enhanced mitochondrial energy metabolism in rat skeletal muscle as a result of acute capsiate treatment. Here, we aimed at investigating noninvasively the effects of chronic capsiate ingestion on metabolic changes occurring in exercising gastrocnemius muscle and at the whole-body level. METHODS: We used an original experimental setup allowing a complete noninvasive investigation of gastrocnemius muscle function in situ using 31-phosphorus magnetic resonance spectroscopy. Whole-body fat composition was determined using magnetic resonance imaging and UCP3 gene expression was measured by quantitative real-time RT-PCR analysis. RESULTS: We found that a 14-day daily administration of capsiate (100 mg kg(-1) body weight) reduced UCP3 gene expression and increased phosphocreatine level at baseline and during the stimulation period in gastrocnemius muscle. During muscle stimulation, pH(i) showed a larger alkalosis in the capsiate group suggesting a lower glycolysis and a compensatory higher aerobic contribution to ATP production. Although the capsiate-treated rats were hyperphagic as compared to control animals, they showed a lower weight gain coupled to a decreased abdominal fat content. CONCLUSION: Overall, our data indicated that capsiate administration contributes to the enhancement of aerobic ATP production and the reduction of body fat content coupled to a UCP3 gene downregulation.
    Mots-clés : Abdominal Fat, Animals, Capsaicin, Down-Regulation, Energy Metabolism, Female, Ion Channels, Mitochondria, Muscle, Mitochondrial Proteins, Muscle, Skeletal, Oxidation-Reduction, Rats, Uncoupling Agents.

  • GIANNESINI B., IZQUIERDO M., LE FUR Y., COZZONE P. J., VERLEYE M., LE GUERN M. - E., GILLARDIN J. - M., BENDAHAN D. “Beneficial effects of citrulline malate on skeletal muscle function in endotoxemic rat.”. European journal of pharmacology [En ligne]. 2009. Vol. 602, n°1, p. 143-147. Disponible sur : < http://dx.doi.org/10.1016/j.ejphar.2008.11.015 > (consulté le no date)
    Résumé : Although citrulline malate (CM; CAS 54940-97-5, Stimol) is used against fatigue states, its anti-asthenic effect remains poorly documented. The objective of this double-blind study was to evaluate the effect of oral ingestion of CM on a rat model of asthenia, using in situ (31)Phosphorus magnetic resonance spectroscopy ((31)P-MRS). Muscle weakness was induced by intraperitoneal injections of Klebsiella pneumoniae endotoxin (lipopolysaccharides at 3 mg/kg) at t(0) and t(0)+24 h. For each animal, muscle function was investigated strictly non-invasively before (t(0)-24 h) and during (t(0)+48 h) endotoxemia, through a standardized rest-stimulation-recovery protocol. The transcutaneous electrical stimulation protocol consisted of 5.7 min of repeated isometric contractions at a frequency of 3.3 Hz, and force production was measured with an ergometer. CM supplementation in endotoxemic animals prevented the basal phosphocreatine/ATP ratio reduction and normalized the intracellular pH (pH(i)) time-course during muscular activity as a sign of an effect at the muscle energetics level. In addition, CM treatment avoided the endotoxemia-induced decline in developed force. These results demonstrate the efficiency of CM for limiting skeletal muscle dysfunction in rats treated with bacterial endotoxin.
    Mots-clés : Administration, Oral, Animals, Citrulline, Double-Blind Method, Endotoxemia, Endotoxins, Energy Metabolism, Hydrogen-Ion Concentration, Klebsiella pneumoniae, Magnetic Resonance Spectroscopy, Malates, Male, Muscle Contraction, Muscle, Skeletal, Physical Exertion, Rats, Rats, Wistar, Time Factors.

  • ODDOUX S., BROCARD J., SCHWEITZER A., SZENTESI P., GIANNESINI B., BROCARD J., FAURé J., PERNET-GALLAY K., BENDAHAN D., LUNARDI J., CSERNOCH L., MARTY I. “Triadin deletion induces impaired skeletal muscle function.”. The Journal of biological chemistry [En ligne]. 2009. Vol. 284, n°50, p. 34918-34929. Disponible sur : < http://dx.doi.org/10.1074/jbc.M109.022442 > (consulté le no date)
    Résumé : Triadin is a multiple proteins family, some isoforms being involved in muscle excitation-contraction coupling, and some having still unknown functions. To obtain clues on triadin functions, we engineered a triadin knock-out mouse line and characterized the physiological effect of triadin ablation on skeletal muscle function. These mice presented a reduced muscle strength, which seemed not to alter their survival and has been characterized in the present work. We first checked in these mice the expression level of the different proteins involved in calcium homeostasis and observed in fast muscles an increase in expression of dihydropyridine receptor, with a large reduction in calsequestrin expression. Electron microscopy analysis of KO muscles morphology demonstrated the presence of triads in abnormal orientation and a reduction in the sarcoplasmic reticulum terminal cisternae volume. Using calcium imaging on cultured myotubes, we observed a reduction in the total amount of calcium stored in the sarcoplasmic reticulum. Physiological studies have been performed to evaluate the influence of triadin deletion on skeletal muscle function. Muscle strength has been measured both on the whole animal model, using hang test or electrical stimulation combined with NMR analysis and strength measurement, or on isolated muscle using electrical stimulation. All the results obtained demonstrate an important reduction in muscle strength, indicating that triadin plays an essential role in skeletal muscle function and in skeletal muscle structure. These results indicate that triadin alteration leads to the development of a myopathy, which could be studied using this new animal model.
    Mots-clés : Animals, Behavior, Animal, Calcium, Carrier Proteins, Cells, Cultured, Female, Gene Deletion, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Muscle Contraction, Muscle Proteins, Muscle, Skeletal, Protein Isoforms, Ryanodine Receptor Calcium Release Channel.

2008

Journal Article

  • GIANNESINI B., IZQUIERDO M., DALMASSO C., LE FUR Y., COZZONE P. J., VERLEYE M., LE GUERN M. - E., GILLARDIN J. - M., BENDAHAN D. “Endotoxemia does not limit energy supply in exercising rat skeletal muscle.”. Muscle & nerve [En ligne]. 2008. Vol. 37, n°4, p. 496-504. Disponible sur : < http://dx.doi.org/10.1002/mus.20966 > (consulté le no date)
    Résumé : Although depletion in high-energy phosphorylated compounds and mitochondrial impairment have been reported in septic skeletal muscle at rest, their impact on energy metabolism has not been documented during exercise. In this study we aimed to investigate strictly gastrocnemius muscle function non-invasively, using magnetic resonance techniques in endotoxemic rats. Endotoxemia was induced by injecting animals intraperitoneally at t(0) and t(0) + 24 h with Klebsiella pneumoniae lipopolysaccharides (at 3 mg kg(-1)). Investigations were performed at t(0) + 48 h during a transcutaneous electrical stimulation protocol consisting of 5.7 min of repeated isometric contractions at a frequency of 3.3 HZ. Endotoxin treatment produced a depletion in basal phosphocreatine content and a pronounced reduction in oxidative adenosine triphosphate (ATP) synthesis capacity, whereas the resting ATP concentration remained unchanged. During the stimulation period, endotoxemia caused a decrease in force-generating capacity that was fully accounted for by the loss of muscle mass. It further induced an acceleration of glycolytic ATP production and an increased accumulation of adenosine diphosphate (ADP, an important mitochondrial regulator) that allowed a near-normal rate of oxidative ATP synthesis. Finally, endotoxemia did not affect the total rate of ATP production or the ATP cost of contraction throughout the whole stimulation period. These data demonstrate that, in an acute septic phase, metabolic alterations in resting muscle do not impact energy supply in exercising muscle, likely as a result of adaptive mechanisms.
    Mots-clés : Adenosine Triphosphate, Animals, crmbm, Endotoxemia, Energy Metabolism, Hydrogen-Ion Concentration, Klebsiella pneumoniae, Lipopolysaccharides, Male, Muscle Contraction, Muscle, Skeletal, Phosphorylation, Physical Exertion, Rats, Rats, Wistar, Sepsis.

  • MARQUESTE T., GIANNESINI B., FUR Y. L., COZZONE P. J., BENDAHAN D. “Comparative MRI analysis of T2 changes associated with single and repeated bouts of downhill running leading to eccentric-induced muscle damage.”. Journal of applied physiology (Bethesda, Md.: 1985) [En ligne]. 2008. Vol. 105, n°1, p. 299-307. Disponible sur : < http://dx.doi.org/10.1152/japplphysiol.00738.2007 > (consulté le no date)
    Résumé : Although the exact mechanisms are still unclear, it is commonly acknowledged that acute eccentric exercise alters muscle performance, whereas the repetition of successive bouts leads to the disappearance of the deleterious signs. To clarify this issue, we measured blood creatine kinase and lactate dehydrogenase activities and proton transverse relaxation time (T2) in various leg muscles 72 h after single and repeated bouts of exhausting downhill running sessions (-15 degrees , 1.5 km/h) with either 4 or 7 days elapsed between bouts. After a single exercise bout, T2 and enzyme activities initially increased and recovered rapidly. When exercise bouts were repeated over a short time period (4 days), initial changes did not recover and endurance time throughout additional exercise sessions was significantly reduced. On the contrary, with a longer resting time between exercises (7 days), the endurance time of additional running sessions was significantly longer and muscle changes (T2 increase, muscle edema, and enzyme activity changes) slowly and completely reversed. Significant correlations were found between T2 changes and enzyme activities. T2 changes in the soleus and gastrocnemius muscle heads were differently affected by lengthening contractions, suggesting a muscle specificity and indicating that muscle alterations might be linked to different anatomical properties, such as fiber pennation angles, typology, and/or the exhausting nature of the downhill running sessions. We documented a "less muscle injury" effect due to the repetition of exercise bouts at a low frequency (i.e., 1 session per week) in accordance with the delayed muscle inflammation. This effect was not observed when the between-exercise resting time was shorter.
    Mots-clés : Animals, Creatine Kinase, crmbm, Electric Stimulation, Enzymes, Female, Hindlimb, Image Processing, Computer-Assisted, Isometric Contraction, L-Lactate Dehydrogenase, Linear Models, Magnetic Resonance Imaging, Muscle, Skeletal, Rats, Rats, Sprague-Dawley, Running.

2007

Journal Article

  • FARAUT B., GIANNESINI B., MATARAZZO V., MARQUESTE T., DALMASSO C., ROUGON G., COZZONE P. J., BENDAHAN D. “Downregulation of uncoupling protein-3 in vivo is linked to changes in muscle mitochondrial energy metabolism as a result of capsiate administration.”. American journal of physiology. Endocrinology and metabolism [En ligne]. 2007. Vol. 292, n°5, p. E1474-1482. Disponible sur : < http://dx.doi.org/10.1152/ajpendo.00292.2006 > (consulté le no date)
    Résumé : Although it has been suggested that the skeletal muscle mitochondrial uncoupling protein-3 (UCP3) is involved in regulating energy expenditure, its role is still poorly understood. In the present study, we aimed at investigating noninvasively, using magnetic resonance techniques, metabolic changes occurring in exercising muscle as a result of capsiate treatment, which has been previously linked to UCP3 upregulation. We showed that capsiate ingestion strongly reduced UCP3 gene expression in rat gastrocnemius muscle. This large underexpression was accompanied by a significant increase in the rate of mitochondrial ATP production and phosphocreatine level both at rest and during muscle stimulation. Similarly, the stimulation-induced ATP fall and ADP accumulation were significantly less after capsiate administration than in untreated rats. The larger oxidative ATP production rate could not be explained by a proportional decrease in the anaerobic component, i.e., glycolysis and phosphocreatine breakdown. In addition, the mechanical performance was not affected by capsiate administration. Finally, the plasma free fatty acid (FFA) level increased in capsiate-treated rats, whereas no significant change was observed after muscle stimulation in the control group. Considering the corresponding enhanced UCP3 mRNA expression occurring in the control group after muscle stimulation, one can suggest that changes in FFA level and UCP3 mRNA expression are not mechanistically correlated. Overall, we have shown that capsiate administration induced a UCP3 downregulation coupled with an increased mitochondrial ATP synthesis, whereas the muscle force-generating capacity was unchanged. This suggests that a decrease in muscle efficiency and/or additional noncontractile ATP-consuming mechanisms result from UCP3 downregulation.
    Mots-clés : Adenosine Diphosphate, Adenosine Triphosphate, Analgesics, Non-Narcotic, Animals, Capsaicin, crmbm, Down-Regulation, Electric Stimulation, Energy Metabolism, Fatty Acids, Nonesterified, Female, Hydrogen-Ion Concentration, Ion Channels, Magnetic Resonance Spectroscopy, Mitochondria, Muscle, Mitochondrial Proteins, Muscle, Skeletal, Phosphocreatine, Rats, Rats, Sprague-Dawley.

  • GIANNESINI B., IZQUIERDO M., DALMASSO C., LE FUR Y., COZZONE P. J., VERLEYE M., LE GUERN M. - E., GILLARDIN J. - M., BENDAHAN D. “Endotoxemia causes a paradoxical intracellular pH recovery in exercising rat skeletal muscle.”. Muscle & nerve [En ligne]. 2007. Vol. 36, n°4, p. 505-514. Disponible sur : < http://dx.doi.org/10.1002/mus.20843 > (consulté le no date)
    Résumé : In resting skeletal muscle, endotoxemia causes disturbances in energy metabolism that could potentially disturb intracellular pH (pH(i)) during muscular activity. We tested this hypothesis using in situ (31)P-magnetic resonance spectroscopy in contracting rat gastrocnemius muscle. Endotoxemia was induced by injecting rats intraperitoneally at t(0) and t(0) + 24 h with Klebsiella pneumoniae endotoxin (lipopolysaccharides at 3 mg/kg) or saline vehicle. Muscle function was investigated strictly noninvasively at t(0) + 48 h through a transcutaneous electrical stimulation protocol consisting of 5.7 minutes of repeated isometric contraction at 3.3 HZ, and force production was measured with an ergometer. At rest, endotoxin treatment did not affect pH(i) and adenosine triphosphate concentration, but significantly reduced phosphocreatine and glycogen contents. Endotoxemia produced both a reduction of isometric force production and a marked linear recovery (0.08 +/- 0.01 pH unit/min) of pH(i) during the second part of the stimulation period. This recovery was not due to any phenomenon of fiber inactivation linked to development of muscle fatigue, and was not associated with any change in intracellular proton buffering, net proton efflux from the cell, or proton turnovers through creatine kinase reaction and oxidative phosphorylation. This paradoxical pH(i) recovery in exercising rat skeletal muscle under endotoxemia is likely due to slowing of glycolytic flux following the reduction in intramuscular glycogen content. These findings may be useful in the follow-up of septic patients and in the assessment of therapies.
    Mots-clés : Adenosine Triphosphate, Analysis of Variance, Animals, crmbm, Endotoxemia, Energy Metabolism, Glycogen, Hydrogen-Ion Concentration, Intracellular Membranes, Magnetic Resonance Spectroscopy, Male, Muscle Contraction, Muscle, Skeletal, Physical Conditioning, Animal, Rats, Rats, Wistar.

2005

Journal Article

  • GIANNESINI B., IZQUIERDO M., LE FUR Y., COZZONE P. J., FINGERLE J., HIMBER J., KÜNNECKE B., VON KIENLIN M., BENDAHAN D. “New experimental setup for studying strictly noninvasively skeletal muscle function in rat using 1H-magnetic resonance (MR) imaging and 31P-MR spectroscopy.”. Magnetic resonance in medicine: official journal of the Society of Magnetic Resonance in Medicine / Society of Magnetic Resonance in Medicine [En ligne]. 2005. Vol. 54, n°5, p. 1058-1064. Disponible sur : < http://dx.doi.org/10.1002/mrm.20637 > (consulté le no date)
    Résumé : Traditional setups for in situ MR investigation of skeletal muscle function in animals use invasive systems for muscle stimulation and force measurement. These systems require surgical preparation and therefore exclude repetitive investigations on the same animal. This article describes a new experimental setup allowing strictly noninvasive MR investigations of muscle function in contracting rat gastrocnemius muscle using 1H-MR imaging and 31P-MR spectroscopy. The novelty of this setup is the integration of two noninvasive systems allowing muscle contraction by transcutaneous stimulation and force measurement with a dedicated ergometer. Muscle function was investigated in 20 rats (275-300 g) through a fatiguing stimulation protocol, either with this noninvasive setup (n = 10) or with a traditional MR setup (n = 10). T2-weighted images demonstrated that transcutaneous stimulation activated mainly the gastrocnemius muscle. Moreover, the changes in force development and in energy metabolism obtained with the noninvasive setup were qualitatively and quantitatively similar to those obtained with the traditional setup. This noninvasive setup is thus suitable for investigating skeletal muscle function in situ. It offers the possibility to repeat investigations in the same animal, avoiding individual variability and enabling longitudinal follow-up studies. This opens up new perspectives in various research areas including pharmaceutical research.
    Mots-clés : Adenosine Triphosphate, Animals, crmbm, Energy Metabolism, Equipment Design, Equipment Failure Analysis, Hindlimb, Image Interpretation, Computer-Assisted, Isometric Contraction, Magnetic Resonance Imaging, Magnetic Resonance Spectroscopy, Male, Muscle, Skeletal, Phosphocreatine, Phosphorus Isotopes, Pilot Projects, Protons, Rats, Rats, Wistar, Stress, Mechanical, Transducers.

2004

Journal Article

  • BENDAHAN D., GIANNESINI B., COZZONE P. J. “Functional investigations of exercising muscle: a noninvasive magnetic resonance spectroscopy-magnetic resonance imaging approach.”. Cellular and molecular life sciences: CMLS [En ligne]. 2004. Vol. 61, n°9, p. 1001-1015. Disponible sur : < http://dx.doi.org/10.1007/s00018-004-3345-3 > (consulté le no date)
    Résumé : Muscle fatigue, which is defined as the decline in muscle performance during exercise, may occur at different sites along the pathway from the central nervous system through to the intramuscular contractile machinery. Historically, both impairment of neuromuscular transmission and peripheral alterations within the muscle have been proposed as causative factors of fatigue development. However, according to more recent studies, muscle energetics play a key role in this process. Intramyoplasmic accumulation of inorganic phosphate (P(i)) and limitation in ATP availability have been frequently evoked as the main mechanisms leading to fatigue. Although attractive, these hypotheses have been elaborated on the basis of experimental results obtained in vitro, and their physiological relevance has never been clearly demonstrated in vivo. In that context, noninvasive methods such as 31-phosphorus magnetic resonance spectroscopy and surface electromyography have been employed to understand both metabolic and electrical aspects of muscle fatigue under physiological conditions. Mapping of muscles activated during exercise is another interesting issue which can be addressed using magnetic resonance imaging (MRI). Exercise-induced T2 changes have been used in order to locate activated muscles and also as a quantitative index of exercise intensity. The main results related to both issues, i.e. the metabolic and electrical aspects of fatigue and the MRI functional investigation of exercising muscle, are discussed in the present review.
    Mots-clés : Animals, crmbm, Electromyography, Exercise, Humans, Magnetic Resonance Imaging, Magnetic Resonance Spectroscopy, Muscle Fatigue, Muscles, Physical Conditioning, Animal.

  • GIANNESINI B., COZZONE P. J., BENDAHAN D. “In vivo MR investigation of skeletal muscle function in small animals.”. Magma (New York, N.Y.) [En ligne]. 2004. Vol. 17, n°3-6, p. 210-218. Disponible sur : < http://dx.doi.org/10.1007/s10334-004-0080-6 > (consulté le no date)
    Résumé : In vivo 31P-MRS investigations have been widely used in small animals to study skeletal muscle function under normal and pathological conditions. Paradoxically in these studies, the benefit provided by 31P-MRS in terms of non-invasiveness is lost because of the utilization of experimental setups that integrate invasive devices for inducing muscle contractions and for measuring mechanical performance. These traditional methodologies, which require surgical preparations, have obvious limitations regarding repeatability in the same animal. The purpose of this review is to highlight the technical aspects of the in vivo MR investigations of skeletal muscle function in small animal models. We will more particularly address the issue related to the invasiveness of different procedures used so far in order to show finally that a further step into non-invasiveness can be achieved, in particular with the support of muscle functional 1H-MRI.
    Mots-clés : Animals, crmbm, Electric Stimulation, Energy Metabolism, Image Interpretation, Computer-Assisted, Magnetic Resonance Imaging, Muscle, Skeletal, Myocardial Contraction, Phosphorus, Protons, Stress, Mechanical.

2003

Journal Article

  • DARQUES J. L., BENDAHAN D., ROUSSEL M., GIANNESINI B., TAGLIARINI F., LE FUR Y., COZZONE P. J., JAMMES Y. “Combined in situ analysis of metabolic and myoelectrical changes associated with electrically induced fatigue.”. Journal of applied physiology (Bethesda, Md.: 1985) [En ligne]. 2003. Vol. 95, n°4, p. 1476-1484. Disponible sur : < http://dx.doi.org/10.1152/japplphysiol.00230.2003 > (consulté le no date)
    Résumé : Electrical muscle stimulation (Mstim) at a low or high frequency is associated with failure of force production, but the exact mechanisms leading to fatigue in this model are still poorly understood. Using 31P magnetic resonance spectroscopy (31PMRS), we investigated the metabolic changes in rabbit tibialis anterior muscle associated with the force decline during Mstim at low (10 Hz) and high (100 Hz) frequency. We also simultaneously recorded the compound muscle mass action potential (M-wave) evoked by direct muscle stimulation, and we analyzed its post-Mstim variations. The 100-Hz Mstim elicited marked M-wave alterations and induced mild metabolic changes at the onset of stimulation followed by a paradoxical recovery of phosphocreatine (PCr) and pH during the stimulation period. On the contrary, the 10-Hz Mstim produced significant PCr consumption and intracellular acidosis with no paradoxical recovery phenomenon and no significant changes in M-wave characteristics. In addition, the force depression was linearly linked to the stimulation-induced acidosis and PCr breakdown. These results led us to conclude that force failure during 100-Hz Mstim only results from an impaired propagation of muscle action potentials with no metabolic involvement. On the contrary, fatigue induced by 10-Hz Mstim is closely associated with metabolic changes with no alteration of the membrane excitability, thereby underlining the central role of muscle energetics in force depression when muscle is stimulated at low frequency. Finally, our results further indicate a reduction of energy cost of contraction when stimulation frequency is increased from 10 to 100 Hz.
    Mots-clés : Acidosis, Action Potentials, Animals, Electric Stimulation, Electrophysiology, Energy Metabolism, Hydrogen-Ion Concentration, Magnetic Resonance Spectroscopy, Muscle Contraction, Muscle Fatigue, Phosphocreatine, Phosphorus, Rabbits, Reaction Time.
  • GIANNESINI B., COZZONE P. J., BENDAHAN D. “Non-invasive investigations of muscular fatigue: metabolic and electromyographic components.”. Biochimie. 2003. Vol. 85, n°9, p. 873-883.
    Résumé : Muscle fatigue, which is defined as the decline in muscle performance during exercise, may occur at different sites along the pathway from the central nervous system through to the intramuscular contractile machinery. Historically, both impairment of neuromuscular transmission and peripheral alterations within the muscle have been proposed to be involved in the development of fatigue. However, according to the more recent studies, muscle energetics would have a key role in this process. Intramyoplasmic accumulation of inorganic phosphate (P(i)) and limitation in ATP availability are frequently proposed as the causative factors of fatigue development. Although attractive, these hypotheses have been elaborated on the basis of experimental results obtained in vitro and their physiological relevance has never been clearly demonstrated in vivo. In that context, non-invasive methods such as 31-phosphorus magnetic resonance spectroscopy ((31)P MRS) and electromyographic (EMG) recordings have been employed to understand both metabolic and electrical aspects of muscle fatigue under physiological condition. The main results of these studies are reviewed in the present paper.
    Mots-clés : Animals, Electromyography, Energy Metabolism, Exercise, Humans, Muscle Fatigue, Muscles, Nuclear Magnetic Resonance, Biomolecular, Phosphorus Isotopes, Physical Exertion.

2002

Journal Article
  • GIANNESINI B., IZQUIERDO M., COZZONE P. J., BENDAHAN D. “Metabolic underpinnings of the paradoxical net phosphocreatine resynthesis in contracting rat gastrocnemius muscle.”. Biochimica et biophysica acta. 2002. Vol. 1553, n°3, p. 223-231.
    Résumé : Net phosphocreatine (PCr) resynthesis during muscle contraction is a paradoxical phenomenon because it occurs under conditions of high energy demand. The metabolic underpinnings of this phenomenon were analyzed non-invasively using 31P-magnetic resonance spectroscopy in rat gastrocnemius muscle (n=11) electrically stimulated (7.6 Hz, 6 min duration) in situ under ischemic and normoxic conditions. During ischemic stimulation, [PCr] initially fell to a steady state (9+/-5% of resting concentration) which was maintained for the last 5 min of stimulation, whereas isometric force production decreased to a non-measurable level beyond 3 min. Throughout normoxic stimulation, [PCr] and force production declined to a steady state after respectively 1 min (5+/-3% of resting concentration) and 3.25 min (21+/-8% of initial value) of stimulation. Contrary to the observations under ischemia, a paradoxical net PCr resynthesis was recorded during the last 2 min of normoxic stimulation and was not accompanied by any improvement in force production. These results demonstrate that the paradoxical net PCr resynthesis recorded in contracting muscle relies exclusively on oxidative energy production and could occur in inactivated fibers, similarly to PCr resynthesis during post-exercise recovery.
    Mots-clés : Adenosine Triphosphate, Anaerobiosis, Animals, Electric Stimulation, Energy Metabolism, Glycolysis, Hindlimb, Hydrogen-Ion Concentration, Isometric Contraction, Magnetic Resonance Spectroscopy, Male, Muscle Contraction, Muscle, Skeletal, Oxidative Phosphorylation, Phosphocreatine, Rats, Rats, Wistar, Time Factors.

2001

Journal Article
  • GIANNESINI B., IZQUIERDO M., CONFORT-GOUNY S., COZZONE P. J., BENDAHAN D. “Time-dependent and indirect effect of inorganic phosphate on force production in rat gastrocnemius exercising muscle determined by 31P-MRS.”. FEBS letters. 2001. Vol. 507, n°1, p. 25-29.
    Résumé : The relationship of inorganic phosphate (P(i)) and its diprotonated form (H(2)PO(4)(-)) to isometric force (F) was analyzed non-invasively using 31P-magnetic resonance spectroscopy. Rat gastrocnemius muscles were electrically stimulated at six different frequencies in order to produce different levels of fatigue. A curvilinear relationship was demonstrated between force production and [P(i)] and [H(2)PO(4)(-)] accumulation. [P(i)] and [H(2)PO(4)(-)] were correlated with F at the end of the stimulation period but not when F was maximal at the early stage of the stimulation period. Interestingly, the respective [P(i)] and [H(2)PO(4)(-)] did not differ significantly between these two stages demonstrating that [P(i)] and [H(2)PO(4)(-)] cannot be considered as direct effectors of fatigue. This time-dependent and indirect effect of [P(i)] and [H(2)PO(4)(-)] on force production might be mediated by calcium ions.
    Mots-clés : Animals, Electric Stimulation, Isometric Contraction, Magnetic Resonance Spectroscopy, Male, Muscle Fatigue, Muscle, Skeletal, Phosphates, Phosphoric Acids, Rats, Rats, Wistar.
  • GIANNESINI B., IZQUIERDO M., LE FUR Y., COZZONE P. J., BENDAHAN D. “In vivo reduction in ATP cost of contraction is not related to fatigue level in stimulated rat gastrocnemius muscle.”. The Journal of physiology. 2001. Vol. 536, n°Pt 3, p. 905-915.
    Résumé : 1. We tested whether the reduction in ATP cost of contraction during in vivo stimulation of rat gastrocnemius muscle was related to fatigue level. 2. Muscles (n = 44) were electrically stimulated to perform 6 min repeated isometric contractions at different frequencies; one non-fatiguing protocol (stimulation at 0.8 Hz) and five fatiguing protocols (2, 3.2, 4, 5.2 and 7.6 Hz) were used. Anaerobic and oxidative ATP turnover rates were measured non-invasively using (31)P-magnetic resonance spectroscopy. 3. At the onset of the stimulation period, no signs of fatigue were measured in the six protocols and ATP cost of contraction did not differ significantly (P = 0.45) among protocols (mean value of 1.76 +/- 0.11 mM (N s)(-1)). 4. For the six protocols, ATP cost of contraction was significantly reduced (P < 0.05) at the end of the stimulation period when compared with the initial value. This reduction did not differ significantly (P = 0.61) among the five fatiguing protocols (averaging 35 +/- 3 % of initial value), whereas isometric force decreased significantly as stimulation frequency increased. No significant correlation (P = 0.87, r(2) = 0.01) was observed between isometric force and ATP cost of contraction at the end of the stimulation period. In addition, this reduction was significantly lower (P < 0.05) for the non-fatiguing protocol (67 +/- 9 % of initial value) when compared with the fatiguing protocols. 5. These results demonstrate that (i) the reduction in ATP cost of contraction during in vivo stimulation of rat gastrocnemius muscle is not related to the fatigue level; (ii) surprisingly, this reduction was significantly larger during the fatiguing protocols compared with the non-fatiguing protocol.
    Mots-clés : Adenosine Triphosphate, Animals, Data Interpretation, Statistical, Electric Stimulation, Glycolysis, Hindlimb, Isometric Contraction, Kinetics, Magnetic Resonance Spectroscopy, Male, Muscle Contraction, Muscle Fatigue, Muscle Relaxation, Muscle, Skeletal, Oxidation-Reduction, Phosphocreatine, Rats, Rats, Wistar.
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