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The mechanisms leading to skeletal limb muscle dysfunction in chronic obstructive pulmonary disease (COPD) have not been fully elucidated. Exhausted muscle regenerative capacity of satellite cells has been evocated, but the capacity of satellite cells to proliferate and differentiate properly remains unknown. Our objectives were to compare the characteristics of satellite cells derived from COPD patients and healthy individuals, in terms of proliferative and differentiation capacities, morphological phenotype and atrophy/hypertrophy signalling, and oxidative stress status. Therefore, we purified and cultivated satellite cells from progressively frozen vastus lateralis biopsies of eight COPD patients and eight healthy individuals. We examined proliferation parameters, differentiation capacities, myotube diameter, expression of atrophy/hypertrophy markers, oxidative stress damages, antioxidant enzyme expression and cell susceptibility to H2 O2 in cultured myoblasts and/or myotubes. Proliferation characteristics and commitment to terminal differentiation were similar in COPD patients and healthy individuals, despite impaired fusion capacities of COPD myotubes. Myotube diameter was smaller in COPD patients (P = 0.015), and was associated with a higher expression of myostatin (myoblasts: P = 0.083; myotubes: P = 0.050) and atrogin-1 (myoblasts: P = 0.050), and a decreased phospho-AKT/AKT ratio (myoblasts: P = 0.022). Protein carbonylation (myoblasts: P = 0.028; myotubes: P = 0.002) and lipid peroxidation (myotubes: P = 0.065) were higher in COPD cells, and COPD myoblasts were significantly more susceptible to oxidative stress. Thus, cultured satellite cells from COPD patients display characteristics of morphology, atrophic signalling and oxidative stress similar to those described in in vivo COPD skeletal limb muscles. We have therefore demonstrated that muscle alteration in COPD can be studied by classical in vitro cellular models.

Scope Cereals are important sources of carbohydrates, but also contain nutrients that could impact adiposity. The contribution of gluten to obesity and the effects of prebiotics—arabinoxylo‐oligosaccharides (AXOS) and fructo‐oligosaccharides (FOS)—that can be extracted from gluten‐containing cereals are analyzed. Methods and results Mice are fed a control diet, Western diet (WD, consisting of high fat/high sucrose), or WD with 5% gluten. Prebiotics are tested in the WD with gluten. Gluten does not increase body weight and has a minor effect on ileal inflammation. Gluten decreases the expression of browning markers in the fat and increases the triglycerides synthesis in the muscle. AXOS decreases body weight and adiposity in fat pads muscle and liver. AXOS promotes gluten cleavage by the induction of prolyl endopeptidase that is translated into a reduction of gluten immunogenic peptides. Gluten has minor effects on cecal microbiota composition, whereas prebiotics increased Bifidobacterium, Butyricicoccus, Prevotella, and Parasutterella, which are all negatively correlated to the cecal content of gluten peptides. Conclusion While gluten may affect metabolic homeostasis, these effects are lessened when gluten is consumed along with cereal‐derived fibers. If confirmed in humans, the authors bring new arguments to eat fiber‐rich cereals to promote a healthy diet., The addition of gluten to the Western diet worsens adiposity in mice. Whether the prebiotics arabinoxylo‐oligosaccharides (AXOS) and fructo‐oligosaccharides (FOS) can counteract the obesogenic effects of gluten is tested. AXOS decreases adiposity and induces the prolyl endopeptidase activity that reduces gluten immunogenic peptides. Prebiotics influence the microbiota composition, increasing Bifidobacterium, Butyricicoccus, Prevotella, and Parasutterella, which are all negatively correlated with gluten peptides.

The AMPK/PGC-1α metabolic pathway and nuclear respiratory factor 1 up-regulate human telomere transcription., DNA breaks activate the DNA damage response and, if left unrepaired, trigger cellular senescence. Telomeres are specialized nucleoprotein structures that protect chromosome ends from persistent DNA damage response activation. Whether protection can be enhanced to counteract the age-dependent decline in telomere integrity is a challenging question. Telomeric repeat–containing RNA (TERRA), which is transcribed from telomeres, emerged as important player in telomere integrity. However, how human telomere transcription is regulated is still largely unknown. We identify nuclear respiratory factor 1 and peroxisome proliferator–activated receptor γ coactivator 1α as regulators of human telomere transcription. In agreement with an upstream regulation of these factors by adenosine 5′-monophosphate (AMP)–activated protein kinase (AMPK), pharmacological activation of AMPK in cancer cell lines or in normal nonproliferating myotubes up-regulated TERRA, thereby linking metabolism to telomere fitness. Cycling endurance exercise, which is associated with AMPK activation, increased TERRA levels in skeletal muscle biopsies obtained from 10 healthy young volunteers. The data support the idea that exercise may protect against aging.

Introduction L’echographie pulmonaire pourrait etre un outil interessant pour le kinesitherapeute puisqu’elle pourrait permettre d’ameliorer l’indication et le suivi du traitement par kinesitherapie respiratoire [1] . A notre connaissance, aucune etude n’a evalue l’impact de l’echographie pulmonaire sur le processus de decision clinique du kinesitherapeute. Ce rapport de cas aborde l’interet de l’echographie pulmonaire en kinesitherapie respiratoire chez une patiente avec une consolidation pulmonaire. Materiel, population et methode Ce rapport de cas est ecrit suivant les recommandations de « The CARE guideline » [2] . La patiente etait une femme de 68 ans, non intubee et hospitalisee dans un service de soins intensifs respiratoires. Elle etait hypoxemique, dyspneique au repos et presentait une opacite radiologique en base pulmonaire droite se majorant. L’examen clinique du kinesitherapeute a retrouve : une diminution de la mobilite thoracique, une matite et une abolition du murmure vesiculaire a la base de l’hemithorax droit, aboutissant a la formulation par le kinesitherapeute de plusieurs hypotheses cliniques : epanchement pleural, atelectasie obstructive ou pneumopathie. Le traitement par kinesitherapie respiratoire differe selon le type de deficience pulmonaire. Il est donc essentiel de determiner la nature des deficiences pulmonaires. Ainsi, le kinesitherapeute a decide de realiser une echographie pulmonaire afin de ne retenir que l’hypothese la plus probable. Resultats L’examen echographique pratique par le kinesitherapeute a mis en evidence la presence d’une consolidation pulmonaire dans les regions infero-laterales et posterieures du poumon droit avec un pattern pneumonique ( Figure 1 ) : presence du signe d’aspect tissulaire, du signe de la limite dechiree, un bronchogramme aerique dynamique et un bronchogramme liquidien. Les informations echographiques ont oriente le kinesitherapeute vers le choix de techniques d’amelioration du recrutement alveolaire : decubitus semi-ventral (cote gauche en infralateral) et ventilation par pression positive continue durant 45 minutes. La reponse du patient au traitement etait controlee par echographie et a montre une diminution de la taille de la consolidation et l’apparition de lignes B, signifiant un gain d’aeration pulmonaire. Conclusion ou discussion L’echographie pulmonaire a permis au kinesitherapeute de preciser la nature des opacites pulmonaires radiologiques. L’apparition de signes de re-aeration pulmonaire montre une reponse positive a court terme a la kinesitherapie respiratoire.

Introduction et but de l’etude Les fructanes de type inuline sont des fibres alimentaires qui conferent des effets benefiques a l’hote, notamment via la modification du microbiote intestinal. Les vegetaux sont la source majoritaire de fructanes et les etudes d’intervention ayant ete menees jusqu’a ce jour se sont focalisees sur les fructanes issus de la racine de chicoree. Dans le cadre du projet Food4Gut, finance par un programme d’excellence de la region Wallonne, nous etudions l’impact des legumes naturellement riches en fructanes sur la sante intestinale ainsi que sur le comportement alimentaire. Materiel et methodes Vingt-six sujets sains ont recu pendant deux semaines un regime a base de legumes riches en inuline (apport d’environ 15 g/j en fructanes). Trois journees tests ont ete organisees : une avant l’intervention, une apres l’intervention et 3 semaines apres retour a leur regime habituel. Les analyses suivantes ont ete realisees : composition du microbiote intestinal, symptomes gastro-intestinaux, fermentation microbienne, comportement alimentaire. Resultats et analyse statistique Le microbiote intestinal est modifie de maniere selective pendant l’intervention (augmentation du genre Bifidobacterium, diminution des Oxalobacteriacea et de certaines Clostridiales, valeurs de p Conclusion La consommation de legumes riches en fructanes s’inscrit dans une approche nutritionnelle saine et permet d’augmenter l’apport en fibres dans la population generale. Cette approche alimentaire est d’ailleurs actuellement evaluee chez des patients obeses, en vue de mettre en evidence le lien entre les changements du microbiote et une potentielle amelioration de l’etat metabolique des patients.

Myostatin, a member of the transforming growth factor-β superfamily, is a potent negative regulator of skeletal muscle growth and is conserved in many species, from rodents to humans. Myostatin inactivation can induce skeletal muscle hypertrophy, while its overexpression or systemic administration causes muscle atrophy. As it represents a potential target for stimulating muscle growth and/or preventing muscle wasting, myostatin regulation and functions in the control of muscle mass have been extensively studied. A wealth of data strongly suggests that alterations in skeletal muscle mass are associated with dysregulation in myostatin expression. Moreover, myostatin plays a central role in integrating/mediating anabolic and catabolic responses. Myostatin negatively regulates the activity of the Akt pathway, which promotes protein synthesis, and increases the activity of the ubiquitin-proteasome system to induce atrophy. Several new studies have brought new information on how myostatin may affect both ribosomal biogenesis and translation efficiency of specific mRNA subclasses. In addition, although myostatin has been identified as a modulator of the major catabolic pathways, including the ubiquitin-proteasome and the autophagy-lysosome systems, the underlying mechanisms are only partially understood. The goal of this review is to highlight outstanding questions about myostatin-mediated regulation of the anabolic and catabolic signaling pathways in skeletal muscle. Particular emphasis has been placed on (1) the cross-regulation between myostatin, the growth-promoting pathways and the proteolytic systems; (2) how myostatin inhibition leads to muscle hypertrophy; and (3) the regulation of translation by myostatin.

PURPOSE: We tested the hypothesis that polyphenol-rich extracts can reduce endoplasmic reticulum (ER) stress induced by a high-fat diet (HFD) in skeletal muscle of mice. METHODS: Mice were randomly assigned to four groups receiving during 20 weeks either a standard chow control (CTRL), or a HFD supplemented, or not, with pomegranate (HFD + P) or green tea (HFD + GT) extracts. After the nutritional intervention, mice were killed and gastrocnemius muscles were taken. Proteins and mRNA were measured by Western blot and RT-qPCR, respectively. RESULTS: Body weight gain and visceral fat were higher in HFD, HFD + P and HFD + GT than in CTRL. The markers of the unfolded protein response BiP, XBP1u, XBP1s and ATF4 were higher only in HFD. In HFD + P and HFD + GT, this increase was not observed except for CHOP, which was elevated in all HFD groups. HFD increased also markers of ubiquitin-proteasome pathway, autophagy and oxidative stress, which were kept low in HFD + P and HFD + GT groups. CONCLUSION: Our data provide evidence for a protective effect of pomegranate and green tea extracts against ER stress, oxidative stress and protein degradation induced by HFD in skeletal muscle. They give arguments for a usefulness of these natural nutritional compounds to fight against cellular dysfunctions related to fat excess. ispartof: European Journal of Nutrition vol:54 issue:3 pages:377-389 ispartof: location:Germany status: published

cope We investigated whether punicalagin-rich pomegranate extract (PE) protects skeletal muscle of mice against inflammation induced by an acute injection of TNF-α. Results Mice fed with PE or standard chow during six weeks were injected with TNF-α (100 ng/g) or vehicle and sacrificed six hours later. Prior supplementation with PE prevented the loss of tibialis anterior mass induced by TNF-α. In skeletal muscle, the activation of the NF-κB signaling and the induction of cytokines mRNA were reduced in mice having received PE. In those mice, the activity of the Akt/mTORC1 pathway and the protein synthesis were maintained after TNF-α injection whereas markers involved in the ubiquitin proteasome pathway were less activated. As urolithin A was the only punicalagin metabolite detectable in plasma of mice supplemented with PE, we performed in vitro experiments using a murine cell line (C2C12) to provide evidence that urolithin A is likely the active compound protecting skeletal muscle against TNF-α-induced inflammation. Conclusion (focus on nutritional relevance) These results suggest that supplementation with a punicalagin-rich pomegranate extract may protect skeletal muscle against an acute inflammation. This article is protected by copyright. All rights reserved

International audience; Myostatin deficiency leads in skeletal muscle overgrowth but the precise molecular mechanisms underlying this hypertrophy are not well understood. In this study, to gain insight into the role of endogenous myostatin in the translational regulation, we used an in vitro model of cultured satellite cells derived from myostatin knock-out mice. Our results show that myostatin knock-out myotubes are larger than control myotubes and that this phenotype is associated with an increased activation of the Akt/mTOR signaling pathway, a known regulator of muscle hypertrophy. These results demonstrate that hypertrophy due to myostatin deficiency is preserved in vitro and suggest that myostatin deletion results in an increased protein synthesis. Accordingly, the rates of global RNA content, polysome formation and protein synthesis are all increased in myostatin-deficient myotubes while they are counteracted by the addition of recombinant myostatin. We furthermore demonstrated that genetic deletion of myostatin stimulates cap-dependent translation by positively regulating assembly of the translation preinitiation complex. Together the data indicate that myostatin controls muscle hypertrophy in part by regulating protein synthesis initiation rates, that is, translational efficiency.

Corresponding author; fax: +33 4 6754 5694. E-mail address: bonnieu@supagro.inra.fr; International audience; Myostatin and hypoxia signalling pathways are able to induce skeletal muscle atrophy, but whether a relationship between these two pathways exists is currently unknown. Here, we tested the hypothesis that a potential mechanism for hypoxia effect on skeletal muscle may be through regulation of myostatin. We reported an induction of myostatin expression in muscles of rats exposed to chronic hypoxia. Interestingly, we also demonstrated increased skeletal muscle myostatin protein expression in skeletal muscle of hypoxemic patients with severe chronic obstructive pulmonary disease (COPD). Parallel studies in human skeletal muscle cell cultures showed that induction of myostatin expression in myotubes treated with hypoxia-mimicking agent such as cobalt chloride (CoCl) is associated with myotube atrophy. Furthermore, we demonstrated that inhibition of myostatin by means of genetic deletion of myostatin or treatment with blocking antimyostatin antibodies inhibits the CoCl-induced atrophy in muscle cells. Finally, addition of recombinant myostatin restored the CoCl induced atrophy in myostatin deficient myotubes. These results strongly suggest that myostatin can play an essential role in the adaptation of skeletal muscle to hypoxic environment.

Le facteur de croissance myostatine initialement identifié chez la souris, est un régulateur négatif de la masse musculaire. Des mutations naturelles ou expérimentales dans le gène codant ce facteur sont à l’origine d’un phénotype d’hypermuscularité, notamment chez les bovins culards. La myostatine régule la myogenèse et la balance atrophie/hypertrophie musculaire. Elle intervient dès la vie foetale en contrôlant la prolifération des cellules musculaires et donc le nombre total de fibres musculaires. Pendant la vie postnatale elle participe au contrôle de la taille des fibres musculaires en régulant l’activité des cellules satellites et la synthèse protéique. Elle est galement impliquée dans la fonte musculaire. Il semblerait qu’elle intervienne aussi dans le contrôle de l’adipogenèse et de l’ostéogenèse. Cette revue fait le point sur l’état des connaissances actuelles concernant l’expression et l’activité de ce facteur et leur régulation moléculaire. Ces données permettront à terme d’envisager une utilisation raisonnée de ces connaissances en agronomie pour la production de viande., In livestock the double-muscled phenotype is well known and has been selected in certain breeds, in order to increase carcass yield . Even though the chromosomal location of the gene responsible for the double-muscled phenotype in cattle has been known for a long time, the gene was identified more recently with studies in mice. In fact, mutations present in the growth factor myostatin gene cause the doublemuscled phenotype. Myostatin is a negative regulator of muscle mass and plays a key role in muscle homeostasis. Myostatin also appears to be involved in the control of adipogenesis and osteogenesis. This review provides an update on the current state of the knowledge of myostatin and on the rational use of such knowledge in agronomy for meat production.