[Force-Velocity-Endurance (FoVE) Model: a new method for functional striated skeletal muscle in situ evaluation in murine models].

The FoVE model is a new theoretical framework coupled with innovative modeling to evaluate the striated skeletal muscle function. The theoretical model is based on two fundamental relationships: the force-velocity relationship and the force-time relationship. These relationships describe the muscle force production capacity as a function of contraction velocity and exercise duration, respectively.

Molecular determinants of skeletal muscle force loss in response to 5 days of dry immersion in human.

Background: Astronauts in Earth's orbit experience microgravity, resulting in a decline of skeletal muscle mass and function. On Earth, models simulating microgravity have shown that the extent of the loss in muscle force is greater than the loss in muscle mass. The reasons behind this disproportionate loss of muscle force are still poorly understood.

Hypothalamic-pituitary-adrenal axis activation and glucocorticoid-responsive gene expression in skeletal muscle and liver of Apc mice.

Background: Cancer patients at advanced stages experience a severe depletion of skeletal muscle compartment together with a decrease in muscle function, known as cancer cachexia. Cachexia contributes to reducing quality of life, treatment efficiency, and lifespan of cancer patients. However, the systemic nature of the syndrome is poorly documented.

Does high mitochondrial efficiency carry an oxidative cost? The case of the African pygmy mouse (Mus mattheyi).

Skeletal muscle mitochondria of the African pygmy mouse Mus mattheyi exhibit markedly reduced oxygen consumption and ATP synthesis rates but a higher mitochondrial efficiency than what would be expected from allometric trends. In the present study, we assessed whether such reduction of mitochondrial activity in M. mattheyi can limit the oxidative stress associated with an increased generation of mitochondrial reactive oxygen species.

Pharmacological inhibition of myostatin improves skeletal muscle mass and function in a mouse model of stroke.

In stroke patients, loss of skeletal muscle mass leads to prolonged weakness and less efficient rehabilitation. We previously showed that expression of myostatin, a master negative regulator of skeletal muscle mass, was strongly increased in skeletal muscle in a mouse model of stroke. We therefore tested the hypothesis that myostatin inhibition would improve recovery of skeletal muscle mass and function after cerebral ischemia.

Regulation of Akt-mTOR, ubiquitin-proteasome and autophagy-lysosome pathways in locomotor and respiratory muscles during experimental sepsis in mice.

Sepsis induced loss of muscle mass and function contributes to promote physical inactivity and disability in patients. In this experimental study, mice were sacrificed 1, 4, or 7 days after cecal ligation and puncture (CLP) or sham surgery. When compared with diaphragm, locomotor muscles were more prone to sepsis-induced muscle mass loss.

Fibroblast growth factor 19 regulates skeletal muscle mass and ameliorates muscle wasting in mice.

The endocrine-derived hormone fibroblast growth factor (FGF) 19 has recently emerged as a potential target for treating metabolic disease. Given that skeletal muscle is a key metabolic organ, we explored the role of FGF19 in that tissue. Here we report a novel function of FGF19 in regulating skeletal muscle mass through enlargement of muscle fiber size, and in protecting muscle from atrophy.

Myostatin gene inactivation prevents skeletal muscle wasting in cancer.

Cachexia is a muscle-wasting syndrome that contributes significantly to morbidity and mortality of many patients with advanced cancers. However, little is understood about how the severe loss of skeletal muscle characterizing this condition occurs. In the current study, we tested the hypothesis that the muscle protein myostatin is involved in mediating the pathogenesis of cachexia-induced muscle wasting in tumor-bearing mice.

Regulation of Akt-mTOR, ubiquitin-proteasome and autophagy-lysosome pathways in response to formoterol administration in rat skeletal muscle.

Administration of β2-agonists triggers skeletal muscle anabolism and hypertrophy. We investigated the time course of the molecular events responsible for rat skeletal muscle hypertrophy in response to 1, 3 and 10 days of formoterol administration (i.p.

Quantitative changes in focal adhesion kinase and its inhibitor, FRNK, drive load-dependent expression of costamere components.

Costameres are mechanosensory sites of focal adhesion in the sarcolemma that reinforce the muscle-fiber composite and provide an anchor for myofibrillogenesis. We hypothesized that elevated content of the integrin-associated regulator of costamere turnover in culture, focal adhesion kinase (FAK), drives changes in costamere component content in antigravity muscle in a load-dependent way in correspondence with altered muscle weight. The content of FAK in soleus muscle being phosphorylated at autoregulatory tyrosine 397 (FAK-pY397) was increased after 20 s of stretch.

β2-Adrenergic agonists and the treatment of skeletal muscle wasting disorders.

β2-Agonists are traditionally used for the treatment of bronchospasm associated with asthma and the treatment of symptomatic patients with COPD. However, β2-agonists are also powerful anabolic agents that trigger skeletal muscle hypertrophy. Investigating the effects of β2-agonists in skeletal muscle over the past 30 years in different animal models has led to the identification of potential therapeutic applications in several muscle wasting disorders, including neuromuscular diseases, cancer cachexia, sepsis or thermal injury.

A centronuclear myopathy--dynamin 2 mutation impairs autophagy in mice.

Dynamin 2 (Dnm2) is involved in endocytosis and intracellular membrane trafficking through its function in vesicle formation from distinct membrane compartments. Heterozygous (HTZ) mutations in the DNM2 gene cause dominant centronuclear myopathy or Charcot-Marie-Tooth neuropathy. We generated a knock-in Dnm2R465W mouse model expressing the most frequent human mutation and recently reported that HTZ mice progressively developed a myopathy.

A centronuclear myopathy-dynamin 2 mutation impairs skeletal muscle structure and function in mice.

Autosomal dominant centronuclear myopathy (AD-CNM) is due to mutations in the gene encoding dynamin 2 (DNM2) involved in endocytosis and intracellular membrane trafficking. To understand the pathomechanisms resulting from a DNM2 mutation, we generated a knock-in mouse model expressing the most frequent AD-CNM mutation (KI-Dnm2(R465W)). Heterozygous (HTZ) mice developed a myopathy showing a specific spatial and temporal muscle involvement.

A hypoxia complement differentiates the muscle response to endurance exercise.

Metabolic stress is believed to constitute an important signal for training-induced adjustments of gene expression and oxidative capacity in skeletal muscle. We hypothesized that the effects of endurance training on expression of muscle-relevant transcripts and ultrastructure would be specifically modified by a hypoxia complement during exercise due to enhanced glycolytic strain. Endurance training of untrained male subjects in conditions of hypoxia increased subsarcolemmal mitochondrial density in the recruited vastus lateralis muscle and power output in hypoxia more than training in normoxia, i.

Dynamin 2 and human diseases.

Dynamin 2 (DNM2) mutations cause autosomal dominant centronuclear myopathy, a rare form of congenital myopathy, and intermediate and axonal forms of Charcot-Marie-Tooth disease, a peripheral neuropathy. DNM2 is a large GTPase mainly involved in membrane trafficking through its function in the formation and release of nascent vesicles from biological membranes. DNM2 participates in clathrin-dependent and clathrin-independent endocytosis and intracellular membrane trafficking (from endosomes and Golgi apparatus).

Dynamin 2 mutations associated with human diseases impair clathrin-mediated receptor endocytosis.

Dynamin 2 (DNM2) is a large GTPase involved in the release of nascent vesicles during endocytosis and intracellular membrane trafficking. Distinct DNM2 mutations, affecting the middle domain (MD) and the Pleckstrin homology domain (PH), have been identified in autosomal dominant centronuclear myopathy (CNM) and in the intermediate and axonal forms of the Charcot-Marie-Tooth peripheral neuropathy (CMT). We report here the first CNM mutation (c.

Focal adhesion kinase is a load-dependent governor of the slow contractile and oxidative muscle phenotype.

Striated muscle exhibits a pronounced structural-functional plasticity in response to chronic alterations in loading. We assessed the implication of focal adhesion kinase (FAK) signalling in mechano-regulated differentiation of slow-oxidative muscle. Load-dependent consequences of FAK signal modulation were identified using a multi-level approach after electrotransfer of rat soleus muscle with FAK-expression plasmid vs.

Down-regulation of Akt/mammalian target of rapamycin signaling pathway in response to myostatin overexpression in skeletal muscle.

Myostatin, a member of the TGF-beta family, has been identified as a master regulator of embryonic myogenesis and early postnatal skeletal muscle growth. However, cumulative evidence also suggests that alterations in skeletal muscle mass are associated with dysregulation in myostatin expression and that myostatin may contribute to muscle mass loss in adulthood. Two major branches of the Akt pathway are relevant for the regulation of skeletal muscle mass, the Akt/mammalian target of rapamycin (mTOR) pathway, which controls protein synthesis, and the Akt/forkhead box O (FOXO) pathway, which controls protein degradation.

Mechano-regulated tenascin-C orchestrates muscle repair.

Tenascin-C (TNC) is a mechano-regulated, morphogenic, extracellular matrix protein that is associated with tissue remodeling. The physiological role of TNC remains unclear because transgenic mice engineered for a TNC deficiency, via a defect in TNC secretion, show no major pathologies. We hypothesized that TNC-deficient mice would demonstrate defects in the repair of damaged leg muscles, which would be of functional significance because this tissue is subjected to frequent cycles of mechanical damage and regeneration.

Kinetic of transgene expression after electrotransfer into skeletal muscle: importance of promoter origin/strength.

We determined over a 3-week period some of the factors that may influence the kinetic of gene expression following in vivo gene electrotransfer. Histochemical analysis of beta-galactosidase and biochemical analysis of luciferase expressions were used to determine reporter gene activity in the Tibialis anterior muscles of young Sprague-Dawley male rats. Transfection efficiency peaked 5 days after gene electrotransfer and then exponentially decreased to reach non-detectable levels at day 28.