scholarly journals The myotendinous junction marker collagen XXII enables zebrafish postural control learning and optimal swimming performance through its force transmission activity

2021 ◽  
Author(s):  
Marilyne Malbouyres ◽  
Alexandre Guiraud ◽  
Christel Lefrancois ◽  
Melanie Salamito ◽  
Pauline Nauroy ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Swimming Performance ◽  
Muscle Performance ◽  
Myotendinous Junction ◽  
Force Transmission ◽  
Skeletal Muscle Function ◽  
Gene Ablation ◽  
Class 1 ◽  
Control Learning ◽  
Degrees Of Severity

Although the myotendinous junction (MTJ) is essential for skeletal muscle integrity, its contribution to skeletal muscle function remains largely unknown. Here, we show that CRISPR-Cas9-mediated gene ablation of the MTJ marker col22a1 in zebrafish identifies two distinctive phenotypic classes: class 1 individuals reach adulthood with no overt muscle phenotype while class 2 display severe movement impairment and eventually dye before metamorphosis. Yet mutants that are unequally affected are all found to display defective force transmission attributed to a loss of ultrastructural integrity of the MTJ and myosepta, though with distinct degrees of severity. The behavior-related consequences of the resulting muscle weakness similarly reveal variable phenotypic expressivity. Movement impairment at the critical stage of swimming postural learning eventually causes class 2 larval death by compromising food intake while intensive exercise is required to uncover a decline in muscle performance in class 1 adults. By confronting MTJ gene expression compensation and structural, functional and behavioral insights of MTJ dysfunction, our work unravels variable expressivity of col22a1 mutant phenotype. This study also underscores COL22A1 as a candidate gene for myopathies associated with dysfunctional force transmission and anticipates a phenotypically heterogeneous disease.

scholarly journals Action of GH on skeletal muscle function: molecular and metabolic mechanisms

2013 ◽  
Vol 52 (1) ◽  
pp. R107-R123 ◽  
Author(s):  
Viral Chikani ◽  
Ken K Y Ho
Keyword(s):  
Skeletal Muscle ◽  
Muscle Function ◽  
The Elderly ◽  
Energy System ◽  
Muscle Performance ◽  
Whole Body ◽  
Target Tissue ◽  
Dependent Manner ◽  
Skeletal Muscle Function ◽  
Body Protein

Skeletal muscle is a target tissue of GH. Based on its anabolic properties, it is widely accepted that GH enhances muscle performance in sports and muscle function in the elderly. This paper critically reviews information on the effects of GH on muscle function covering structure, protein metabolism, the role of IGF1 mediation, bioenergetics and performance drawn from molecular, cellular and physiological studies on animals and humans. GH increases muscle strength by enhancing muscle mass without affecting contractile force or fibre composition type. GH stimulates whole-body protein accretion with protein synthesis occurring in muscular and extra-muscular sites. The energy required to power muscle function is derived from a continuum of anaerobic and aerobic sources. Molecular and functional studies provide evidence that GH stimulates the anaerobic and suppresses the aerobic energy system, in turn affecting power-based functional measures in a time-dependent manner. GH exerts complex multi-system effects on skeletal muscle function in part mediated by the IGF system.

A 2D Finite Element Model of Lateral Transmission of Force in Skeletal Muscle

2011 ◽  
Author(s):  
Chi Zhang ◽  
Yingxin Gao
Keyword(s):  
Skeletal Muscle ◽  
Extracellular Matrix ◽  
Body Movement ◽  
Element Model ◽  
Myotendinous Junction ◽  
Force Transmission ◽  
Multinucleated Cells ◽  
Skeletal Muscle Contraction ◽  
Lateral Transmission ◽  
Surrounding Extracellular Matrix

Skeletal muscle has a complex hierarchical structure which is mainly composed of myofibers and the surrounding extracellular matrix (ECM) including endomysium, perimysium, and epimysium. Myofibers are long, cylindrical, multinucleated cells composed of repeating sarcomeres, which are basic functional units for skeletal muscle contraction. In order to produce body movement, the force generated by myofiber has to be transmitted from individual fiber to the tendon. The commonly accepted site for force transmission is the myotendinous junction (MTJ) where the myofibers connect to the tendon. However, the myofibers mainly end within the muscle fascicles without reaching the MTJ in many muscles, in which case the force has to be transmitted laterally to adjacent fiber through shear and to the tendon eventually.

scholarly journals Effects of Statins on Skeletal Muscle: A Perspective for Physical Therapists

2010 ◽  
Vol 90 (10) ◽  
pp. 1530-1542 ◽  
Author(s):  
Stephanie L. Di Stasi ◽  
Toran D. MacLeod ◽  
Joshua D. Winters ◽  
Stuart A. Binder-Macleod
Keyword(s):  
Skeletal Muscle ◽  
Side Effects ◽  
Physical Therapists ◽  
Physical Therapist ◽  
The United States ◽  
Muscle Performance ◽  
Blood Cholesterol ◽  
Lipid Lowering ◽  
Skeletal Muscle Function ◽  
Statin Use

Hyperlipidemia, also known as high blood cholesterol, is a cardiovascular health risk that affects more than one third of adults in the United States. Statins are commonly prescribed and successful lipid-lowering medications that reduce the risks associated with cardiovascular disease. The side effects most commonly associated with statin use involve muscle cramping, soreness, fatigue, weakness, and, in rare cases, rapid muscle breakdown that can lead to death. Often, these side effects can become apparent during or after strenuous bouts of exercise. Although the mechanisms by which statins affect muscle performance are not entirely understood, recent research has identified some common causative factors. As musculoskeletal and exercise specialists, physical therapists have a unique opportunity to identify adverse effects related to statin use. The purposes of this perspective article are: (1) to review the metabolism and mechanisms of actions of statins, (2) to discuss the effects of statins on skeletal muscle function, (3) to detail the clinical presentation of statin-induced myopathies, (4) to outline the testing used to diagnose statin-induced myopathies, and (5) to introduce a role for the physical therapist for the screening and detection of suspected statin-induced skeletal muscle myopathy.

scholarly journals Time-restricted feeding promotes skeletal muscle function in diet- and genetic-induced obesity through shared and unique pathways

2021 ◽  
Author(s):  
Christopher Livelo ◽  
Yiming Guo ◽  
Shweta Varshney ◽  
Farah Abou Daya ◽  
Hiep Le ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Function ◽  
De Novo ◽  
Tca Cycle ◽  
Glycogen Metabolism ◽  
Fruit Fly ◽  
Muscle Performance ◽  
Restricted Feeding ◽  
Skeletal Muscle Function ◽  
Atp Levels

Abstract Obesity caused by genetic predisposition, a lifestyle of calorie-dense diets and/or circadian disruption can result in complications including metabolic syndrome, cardiovascular disease, and compromised muscle function. By employing time-restricted feeding (TRF), where daily feeding was limited to 12 hours during the day, we observed improved skeletal muscle function compared to ad libitum feeding (ALF). This was observed in both diet-induced obesity (DIO) and genetic-induced obesity (GIO) in a Drosophila melanogaster (fruit fly) model. We evaluated the mechanistic basis of TRF-mediated benefits by utilizing muscle transcriptomic data of indirect flight muscle (IFM) followed by genetic validations, cytological and biochemical evidences. Significant upregulation of glycine N methyltransferase (Gnmt), sarcosine dehydrogenase (Sardh), CG5955 and downregulation of diacylglycerol o-acyltransferase 2 (Dgat2) were commonly induced by TRF intervention under both obese conditions. Moreover, genetic inhibition of Gnmt, Sardh and CG5955 leads to skeletal muscle dysfunction, aberrant lipid accumulation and loss of TRF-mediated benefits. However, skeletal muscle-specific knockdown (KD) of Dgat2 retained muscle function during aging, a result that mimics TRF-mediated benefits. Furthermore, de novo purine biosynthesis appeared to be upregulated specifically in the DIO model under TRF which led to increased ATP levels resulting in improved muscle performance. Additionally, genes associated with AMP kinase (AMPK) signaling, glycogen metabolism, glycolysis, tricarboxylic acid (TCA) cycle and electron transport chain (ETC) signaling were specifically upregulated in GIO model under TRF. TRF mediated benefits in GIO via activation of AMPK, which led to increased ATP levels. Altogether, we identify the shared and distinct pathways in the regulation of muscle function under TRF, which may aid further research and alternative therapeutic avenues that focus on combating comorbidities linked with obesity.

scholarly journals Chronic atorvastatin and exercise can partially reverse established skeletal muscle microvasculopathy in metabolic syndrome

2018 ◽  
Vol 315 (4) ◽  
pp. H855-H870 ◽  
Author(s):  
Kent A. Lemaster ◽  
Stephanie J. Frisbee ◽  
Luc Dubois ◽  
Nikolaos Tzemos ◽  
Fan Wu ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Metabolic Syndrome ◽  
Vascular Function ◽  
Microvascular Dysfunction ◽  
Vascular Wall ◽  
Muscle Performance ◽  
Vascular Structure ◽  
Skeletal Muscle Function ◽  
Targeted Interventions ◽  
Wall Stiffness

It has long been known that chronic metabolic disease is associated with a parallel increase in the risk for developing peripheral vascular disease. Although more clinically relevant, our understanding about reversing established vasculopathy is limited compared with our understanding of the mechanisms and development of impaired vascular structure/function under these conditions. Using the 13-wk-old obese Zucker rat (OZR) model of metabolic syndrome, where microvascular dysfunction is sufficiently established to contribute to impaired skeletal muscle function, we imposed a 7-wk intervention of chronic atorvastatin treatment, chronic treadmill exercise, or both. By 20 wk of age, untreated OZRs manifested a diverse vasculopathy that was a central contributor to poor muscle performance, perfusion, and impaired O2 exchange. Atorvastatin or exercise, with the combination being most effective, improved skeletal muscle vascular metabolite profiles (i.e., nitric oxide, PGI2, and thromboxane A2 bioavailability), reactivity, and perfusion distribution at both individual bifurcations and within the entire microvascular network versus responses in untreated OZRs. However, improvements to microvascular structure (i.e., wall mechanics and microvascular density) were less robust. The combination of the above improvements to vascular function with interventions resulted in an improved muscle performance and O2 transport and exchange versus untreated OZRs, especially at moderate metabolic rates (3-Hz twitch contraction). These results suggest that specific interventions can improve specific indexes of function from established vasculopathy, but either this process was incomplete after 7-wk duration or measures of vascular structure are either resistant to reversal or require better-targeted interventions. NEW & NOTEWORTHY We used atorvastatin and/or chronic exercise to reverse established microvasculopathy in skeletal muscle of rats with metabolic syndrome. With established vasculopathy, atorvastatin and exercise had moderate abilities to reverse dysfunction, and the combined application of both was more effective at restoring function. However, increased vascular wall stiffness and reduced microvessel density were more resistant to reversal. Listen to this article’s corresponding podcast at https://ajpheart.podbean.com/e/reversal-of-microvascular-dysfunction/ .

scholarly journals Protein Kinase D1 Stimulates MEF2 Activity in Skeletal Muscle and Enhances Muscle Performance

2008 ◽  
Vol 28 (11) ◽  
pp. 3600-3609 ◽  
Author(s):  
Mi-Sung Kim ◽  
Jens Fielitz ◽  
John McAnally ◽  
John M. Shelton ◽  
Douglas D. Lemon ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Kinase ◽  
Class Ii ◽  
Muscle Performance ◽  
Type I ◽  
Type Ii ◽  
Muscle Adaptation ◽  
Skeletal Muscle Function ◽  
Protein Kinase D1 ◽  
Slow Twitch

ABSTRACT Skeletal muscle consists of type I and type II myofibers, which exhibit different metabolic and contractile properties. Type I fibers display an oxidative metabolism and are resistant to fatigue, whereas type II fibers are primarily glycolytic and suited for rapid bursts of activity. These properties can be modified by changes in workload, activity, and hormonal stimuli, facilitating muscle adaptation to physiological demand. The MEF2 transcription factor promotes the formation of slow-twitch (type I) muscle fibers in response to activity. MEF2 activity is repressed by class II histone deacetylases (HDACs) and is enhanced by calcium-regulated protein kinases that promote the export of class II HDACs from the nucleus to the cytoplasm. However, the identities of skeletal muscle class II HDAC kinases are not well defined. Here we demonstrate that protein kinase D1 (PKD1), a highly effective class II HDAC kinase, is predominantly expressed in type I myofibers and, when misexpressed in type II myofibers, promotes transformation to a type I, slow-twitch, fatigue-resistant phenotype. Conversely, genetic deletion of PKD1 in type I myofibers increases susceptibility to fatigue. PKD1 cooperates with calcineurin to facilitate slow-twitch-fiber transformation. These findings identify PKD1 as a key regulator of skeletal muscle function and phenotype.

scholarly journals β2-adrenergic receptor agonist counteracts skeletal muscle atrophy and oxidative stress in uremic mice

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Takaaki Higashihara ◽  
Hiroshi Nishi ◽  
Koji Takemura ◽  
Hiroshi Watanabe ◽  
Toru Maruyama ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Adrenergic Receptor ◽  
Culture Media ◽  
Therapeutic Interventions ◽  
Skeletal Muscle Atrophy ◽  
C2c12 Myotubes ◽  
Ros Generation ◽  
Skeletal Muscle Function ◽  
Ros Accumulation ◽  
Β2 Adrenergic Receptor

AbstractIn patients with chronic kidney disease, skeletal muscle dysfunction is associated with mortality. Uremic sarcopenia is caused by ageing, malnutrition, and chronic inflammation, but the molecular mechanism and potential therapeutics have not been fully elucidated yet. We hypothesize that accumulated uremic toxins might exert a direct deteriorative effect on skeletal muscle and explore the pharmacological treatment in experimental animal and culture cell models. The mice intraperitoneally injected with indoxyl sulfate (IS) after unilateral nephrectomy displayed an elevation of IS concentration in skeletal muscle and a reduction of instantaneous muscle strength, along with the predominant loss of fast-twitch myofibers and intramuscular reactive oxygen species (ROS) generation. The addition of IS in the culture media decreased the size of fully differentiated mouse C2C12 myotubes as well. ROS accumulation and mitochondrial dysfunction were also noted. Next, the effect of the β2-adrenergic receptor (β2-AR) agonist, clenbuterol, was evaluated as a potential treatment for uremic sarcopenia. In mice injected with IS, clenbuterol treatment increased the muscle mass and restored the tissue ROS level but failed to improve muscle weakness. In C2C12 myotubes stimulated with IS, although β2-AR activation also attenuated myotube size reduction and ROS accumulation as did other anti-oxidant reagents, it failed to augment the mitochondrial membrane potential. In conclusion, IS provokes muscular strength loss (uremic dynapenia), ROS generation, and mitochondrial impairment. Although the β2-AR agonist can increase the muscular mass with ROS reduction, development of therapeutic interventions for restoring skeletal muscle function is still awaited.

scholarly journals Gait disturbances and muscle dysfunction in fibroblast growth factor 2 knockout mice

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
C. Homer-Bouthiette ◽  
L. Xiao ◽  
Marja M. Hurley
Keyword(s):  
Skeletal Muscle ◽  
Growth Factor ◽  
Muscle Strength ◽  
Fibroblast Growth Factor ◽  
Muscle Function ◽  
Fibroblast Growth Factor 2 ◽  
Fibroblast Growth ◽  
Skeletal Muscle Function ◽  
Age Related ◽  
Gait Disturbances

AbstractFibroblast growth factor 2 (FGF2) is important in musculoskeletal homeostasis, therefore the impact of reduction or Fgf2 knockout on skeletal muscle function and phenotype was determined. Gait analysis as well as muscle strength testing in young and old WT and Fgf2KO demonstrated age-related gait disturbances and reduction in muscle strength that were exacerbated in the KO condition. Fgf2 mRNA and protein were significantly decreased in skeletal muscle of old WT compared with young WT. Muscle fiber cross-sectional area was significantly reduced with increased fibrosis and inflammatory infiltrates in old WT and Fgf2KO vs. young WT. Inflammatory cells were further significantly increased in old Fgf2KO compared with old WT. Lipid-related genes and intramuscular fat was increased in old WT and old Fgf2KO with a further increase in fibro-adipocytes in old Fgf2KO compared with old WT. Impaired FGF signaling including Increased β-Klotho, Fgf21 mRNA, FGF21 protein, phosphorylated FGF receptors 1 and 3, was observed in old WT and old Fgf2KO. MAPK/ ERK1/2 was significantly increased in young and old Fgf2KO. We conclude that Fgf2KO, age-related decreased FGF2 in WT mice, and increased FGF21 in the setting of impaired Fgf2 expression likely contribute to impaired skeletal muscle function and sarcopenia in mice.

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