Proportion Of Slow Muscle Fibers Research Articles

Saponin extract from Achyranthes bidentata Blume alleviates disuse-induced muscle atrophy through PI3K/Akt signaling pathway

Ethnopharmacological relevanceThe roots of Achyranthes bidentata Blume are one of the regularly used herbal drugs in Chinese medicine, and has been applied for strengthening the muscle and bone for a long time. However, its effect on muscle remains unclear. Aim of the studyThis paper aims to explore the anti-muscle atrophy effect of A. bidentata, and to clarify the possible signaling pathways involved. Materials and methodsThe saponin extract of the roots of A. bidentata (ABSE) was prepared and analyzed, and its activity on myoblast differentiation was assayed with C2C12 cell culture. ABSE was then orally administered at dosage of 35, 70 and 140 mg/kg/day to disuse-induced muscle atrophy mice. The studies on mice body weight and muscle quality were conducted, and Western blot was used for exploring the possible signaling pathways involved in the muscle protective action aided with transcriptome analysis. ResultsThe total saponin content of ABSE was 59.1%. ABSE promoted the C2C12 cells differentiation to myotube in C2C12 differentiation assay. Further study with disuse-induced muscle atrophy mice model demonstrated that ABSE significantly increased muscle fiber diameter as well as the proportion of slow muscle fibers. Possible mechanism study aided with transcriptome analysis revealed that ABSE alleviated muscle atrophy at least through activation of PI3K/Akt pathway in vivo & vitro. ConclusionsThe saponin extract of the root of A. bidentata (ABSE) has a protective effect on muscle atrophy, and showed a considerable potential in prevention and treatment of muscle atrophy.

Integration of multi-omics data reveals cis-regulatory variants that are associated with phenotypic differentiation of eastern from western pigs

BackgroundThe genetic mechanisms that underlie phenotypic differentiation in breeding animals have important implications in evolutionary biology and agriculture. However, the contribution of cis-regulatory variants to pig phenotypes is poorly understood. Therefore, our aim was to elucidate the molecular mechanisms by which non-coding variants cause phenotypic differences in pigs by combining evolutionary biology analyses and functional genomics.ResultsWe obtained a high-resolution phased chromosome-scale reference genome with a contig N50 of 18.03 Mb for the Luchuan pig breed (a representative eastern breed) and profiled potential selective sweeps in eastern and western pigs by resequencing the genomes of 234 pigs. Multi-tissue transcriptome and chromatin accessibility analyses of these regions suggest that tissue-specific selection pressure is mediated by promoters and distal cis-regulatory elements. Promoter variants that are associated with increased expression of the lysozyme (LYZ) gene in the small intestine might enhance the immunity of the gastrointestinal tract and roughage tolerance in pigs. In skeletal muscle, an enhancer-modulating single-nucleotide polymorphism that is associated with up-regulation of the expression of the troponin C1, slow skeletal and cardiac type (TNNC1) gene might increase the proportion of slow muscle fibers and affect meat quality.ConclusionsOur work sheds light on the molecular mechanisms by which non-coding variants shape phenotypic differences in pigs and provides valuable resources and novel perspectives to dissect the role of gene regulatory evolution in animal domestication and breeding.

Construction and Analysis of Disuse Atrophy Model of the Gastrocnemius Muscle in Chicken.

Disuse muscle atrophy is identified as the physiological, biochemical, morphological, and functional changes during restricted movement, immobilization, or weightlessness. Although its internal mechanism has been extensively studied in mammals and was thought to be mainly related to oxidative stress, it was unclear whether it behaved consistently in non-mammals such as chickens. In this study, we tried to construct a disuse atrophy model of the gastrocnemius muscle in chickens by limb immobilization, and collected the gastrocnemius muscles of the fixed group and the control group for RNA sequencing. Through analysis of muscle loss, HE staining, immunohistochemistry, and oxidative stress level, we found that limb immobilization could lead to loss of muscle mass, decrease in muscle fiber diameter, decrease in the proportion of slow muscle fibers, and increase in the proportion of fast muscle fibers, and also cause elevated levels of oxidative stress. In addition, a total of 565 different expression genes (DEGs) were obtained by RNA sequencing, which was significantly enriched in the biological processes such as cell proliferation and apoptosis, reactive oxygen species metabolism, and fast and slow muscle fiber transformation, and it showed that the FOXO signaling pathway, closely related to muscle atrophy, was activated. In brief, we initially confirmed that limb immobilization could induce disuse atrophy of skeletal muscle, and oxidative stress was involved in the process of disuse muscle atrophy.

Exercise Capacity Is Improved by Levosimendan in Heart Failure and Sarcopenia via Alleviation of Apoptosis of Skeletal Muscle.

BackgroundPatients suffering from chronic heart failure (CHF) show an increased prevalence of sarcopenia. Levosimendan is an effective drug for the treatment of heart failure, but its effect on sarcopenia is still unclear. We aimed to explore whether levosimendan could enhance skeletal muscle contractibility, improve skeletal muscle atrophy, and thus improve exercise tolerance of individuals with heart failure.MethodsC57BL6/J mice were used to establish the heart failure with sarcopenia model and injected of levosimendan. Mice were separated into control group, sham operation group, HF group, HF + solvent group, HF + levosimendan group, HF + sarcopenia group, HF + sarcopenia + solvent group, HF + sarcopenia + levosimendan group (n = 5–12). After the treatment, exercise capacity and cardiac function were evaluated. Muscle morphology, inflammation level and apoptosis levels were detected, in which mitochondrial function and oxidative stress level were also assessed.ResultLevosimendan could increase forelimb grip strength/body weight, hanging impulse, maximum running distance and time in mice with HF and sarcopenia (P < 0.0001 for all), and these improvements were independent of EF (P = 0.0019 for hanging impulse, P < 0.001 for forelimb grip strength/body weight and maximum running distance). Levosimendan directly increased the CSA of gastrocnemius in mice with HF and sarcopenia (P < 0.0001). After levosimendan injection, the proportion of slow muscle fibers increased (P < 0.0001), but this improvement of muscle fiber typing might be attributed to improved cardiac function (P > 0.05). Levosimendan also maintained mitochondrial membrane potential, decreased cleaved caspase-3 (P = 0.034), cleaved caspase-9 (P < 0.0001), Bax expression (P < 0.0001), and increased Bcl2 expression (P = 0.0036). This effect is independent of improved cardiac function (P = 0.028 for bax, P < 0.001 for cleaved caspase-9 and Bcl2). IL-6, TNF-α expression (P < 0.0001 for both) decreased, and SOD activity (P = 0.0038), GSH/GSSG ratio (P = 0.002) significantly increased in skeletal muscle after injection of levosimendan. The improvement in oxidative stress level was attributed to improved cardiac function (P > 0.05).ConclusionLevosimendan reduce the loss of skeletal muscle mitochondrial membrane potential, decrease the apoptosis, alleviate the inflammation and oxidative stress, and ultimately improve the exercise capacity of mice with heart failure and sarcopenia. Therefore, levosimendan may be a potential drug for the treatment of heart failure with sarcopenia.

Masticatory muscle function affects the pathological conditions of dentofacial deformities.

SummaryThe causes of dentofacial deformities include various known syndromes, genetics, environmental and neuromuscular factors, trauma, and tumors. Above all, the functional effects of muscles are important, and deformation of the mandible is often associated with a mechanical imbalance of the masticatory muscles.With the vertical position of the face, weakness of the sling of the masseter muscle and medial pterygoid muscle causes dilatation of the mandibular angle. In patients with a deep bite, excessive function of the masticatory muscles is reported.Myosin heavy chain (MyHC) properties also affect jawbone morphology. In short-face patients, the proportion of type II fibers, which are fast muscles, is high. The proportions of muscle fiber types are genetically determined but can be altered by postnatal environmental factors. Orthognathic surgery may results in the transition of MyHC to type II (fast) fibers, but excessive stretching enhances the release of inflammatory mediators and causes a shift toward a greater proportion of slow muscle fibers. This feature can be related to postoperative relapse.Bones and muscles are in close crosstalk, and it may be possible to use biochemical approaches as well as biomechanical considerations for the treatment of jaw deformities.

Mesenchymal Stem Cell Treatment of Disc Lesion Prevents Fatty Infiltration and Fibrosis, but not Muscle Fibre Transformation of the Multifidus Muscle

IntroductionThe multifidus muscle undergoes structural and behavioral changes with back pain and injury. After intervertebral disc (IVD) lesion in animals the multifidus muscle undergoes a transformation of muscle fiber types from slow-to-fast, and extensive structural remodelling with increased adipose and connective tissue. Increased expression of pro-inflammatory cytokines (tumor necrosis factor (TNF) and interleukin 1β (ΙΛ−1β)) parallel these changes and may be responsible. Treatment of IVD lesions with mesenchymal stem cells (MSC) prevents or restores loss of IVD height and proteoglycans in the nucleus pulposus, depending on the timing of application. Whether the resolution of IVD changes by MCS treatment prevents or restores changes in the multifidus muscle structure and muscle fiber composition is unknown. This study aimed to investigate whether muscle changes are prevented or restored by early or late MSC treatment of the IVD lesion, respectively, and whether this is related to modification of inflammatory cytokine expression. Material and MethodsThe L1–2 and L3–4 IVDs of 18 sheep received left anterolateral partial thickness annular lesions. Six control sheep underwent no surgery. At four (3-month (n = 6) and 6-month acute (n = 6) treatment groups) or twelve (established (n = 6) treatment group) weeks after initial surgery, animals received MSC injections (0.2ml) to the operated IVD. Three (3-month acute treatment group) and six (6-month acute and established treatment groups) months after initial surgery the L4 multifidus muscle was harvested for muscle fiber type analysis using immunohistochemistry and evaluation of cross sectional area (CSA) of muscle, adipose and connective tissue using standard histology. L2 muscle was harvested for quantitative PCR measures of pro-inflammatory cytokine gene expression (TNF, ΙΛ−1β). ResultsUnlike the response to IVD lesion without MSC treatment (increased connective tissue and adipose CSA), acute MSC treatment prevented increase in adipose (acute treatment=control at 3- and 6-months; p = 0.28 and p = 0.07) and connective tissue CSA (acute treatment < control at 3-months; p < 0.001, acute=control at 6-months; p = 0.39). This paralleled reduced expression of IL-1β at 3-months (acute treatment versus control; p < 0.001). MCS treatment of established treatment animals restored adipose and connective tissue CSA (established treatment=control at 6 months; P > 0.60). The effect of MSC on muscle CSA depended on the treatment timing. At 6 months, acute treatment animals had larger whole muscle CSA than controls (p = 0.002). Control and established treatment animals did not differ (p = 0.73). Despite optimistic data for tissue CSA, muscle harvested at 6 months showed reduced proportion of slow muscle fibers and increased intermediate fibers throughout the multifidus muscle (acute and established treatment group versus control; p < 0.05). TNF expression was greater at 6 months in acute and established treatment groups than control (p < 0.001). ConclusionThese results indicate that MSC treatment of the IVD lesion prevents and restores muscle structural changes, but is unable to prevent changes to multifidus muscle fiber type. This is likely to have functional relevance for neuromuscular control of the healed IVD. MSC appear to have and anti-inflammatory effect on muscle in the early phase when IVD is healing, but cannot influence the later elevation of TNF, which appears destructive for muscle fibers.

The Kenyan runners

Today the Kenyan dominance in middle- and long-distance running is so profound that it has no equivalence to any other sport in the world. Critical physiological factors for performance in running include maximal oxygen consumption (VO2max), fractional VO2max utilization and running economy (energetic cost of running). Kenyan and non-Kenyan elite runners seem to be able to reach very high, but similar maximal oxygen uptake levels just as there is some indication that untrained Kenyans and non-Kenyans have a similar VO2max. In addition, the fractional utilization of VO2max seems to be very high but similar in Kenyan and European runners. Similarly, no differences in the proportion of slow muscle fibers have been observed when comparing Kenyan elite runners with their Caucasian counterparts. In contrast, the oxygen cost of running at a given running velocity has been found to be lower in Kenyan elite runners relative to other elite runners and there is some indication that this is due to differences in body dimensions. Pulmonary system limitations have been observed in Kenyan runners in the form of exercise-induced arterial hypoxemia, expiratory flow limitation, and high levels of respiratory muscle work. It appears that Kenyan runners do not possess a pulmonary system that confers a physiological advantage. Additional studies on truly elite Kenyan runners are necessary to understand the underlying physiology which permits extraordinary running performances.

Can Proinflammatory Cytokine Gene Expression Explain Multifidus Muscle Fiber Changes After an Intervertebral Disc Lesion?

Longitudinal case-controlled animal study. To investigate the effect of an intervertebral disc (IVD) lesion on the proportion of slow, fast, and intermediate muscle fiber types in the multifidus muscle in sheep, and whether muscle fiber changes were paralleled by local gene expression of the proinflammatory cytokines tumor necrosis factor α (TNF-α) and interleukin 1-β. Structure and behavior of the multifidus muscle change in acute and chronic back pain, but the mechanisms are surprisingly poorly understood and the link between structure and behavior is tenuous. Although changes in muscle fiber types have the potential to unify the observations, the effect of injury on muscle fiber distribution has not been adequately tested, and understanding of possible mechanisms is limited. The L1-L2, L3-L4, and L5-L6 IVDs of 11 castrated male sheep received anterolateral lesions. Six control sheep underwent no surgical procedures. Multifidus muscle tissue was harvested at L4 for muscle fiber analysis using immunohistochemistry and L2 for cytokine analysis with polymerase chain reaction for local gene expression of TNF-α and interleukin-1β. The proportion of slow muscle fibers in multifidus was significantly less in the lesioned animals both ipsilateral and contralateral to the IVD lesion. The greatest reduction in slow fibers was in the deep medial muscle region. A greater prevalence of intermediate fibers on the uninjured side implies a delayed fiber-type transformation on that side. TNF-α gene expression in multifidus was greater on both sides in the lesion animals than in the muscle of control animals. Interleukin-1β was increased only on the injured side. These data provide evidence of muscle fiber changes after induction of an IVD lesion and a parallel increase in TNF-α expression. Proinflammatory cytokine changes provide a novel mechanism to explain behavioral and structural changes in multifidus. N/A.

Neuromuscular Specializations within Human Pharyngeal Constrictor Muscles

At present it is believed that the pharyngeal constrictor (PC) muscles are innervated by the vagus (X) nerve and are homogeneous in muscle fiber content. This study tested the hypothesis that adult human PCs are divided into 2 distinct and specialized layers: a slow inner layer (SIL), innervated by the glossopharyngeal (IX) nerve, and a fast outer layer (FOL), innervated by nerve X. Eight normal adult human pharynges (16 sides) obtained from autopsies were studied to determine 1) their gross motor innervation by use of Sihler's stain; 2) their terminal axonal branching by use of acetylcholinesterase (AChE) and silver stain; and 3) their myosin heavy chain (MHC) expression in PC muscle fibers by use of immunocytochemical and immunoblotting techniques. In addition, the specialized nature of the 2 PC layers was also studied in developmental (newborn, neonate, and senescent humans), pathological (adult humans with idiopathic Parkinson's disease [IPD]), and comparative (nonhuman primate [adult macaque monkey]) specimens. When nerves IX and X were traced from their cranial roots to their intramuscular termination in Sihler's-stained specimens, it was seen that nerve IX supplied the SIL, whereas branches of nerve X innervated the FOL in the adult human PCs. Use of AChE and silver stain confirmed that nerve IX branches supplying the SIL contained motor axons and innervated motor end plates. In addition to distinct motor innervation, the SIL contained muscle fibers expressing slow-tonic and alpha-cardiac MHC isoforms, whereas the FOL contained muscle fibers expressing developmental MHC isoforms. In contrast, the FOL became obscured in the elderly and in the adult humans with IPD because of an increased proportion of slow muscle fibers. Notably, distinct muscle fiber layers were not found in the human newborn and nonhuman primate (monkey), but were identified in the 2-year-old human. Human PCs appear to be organized into functional fiber layers, as indicated by distinct motor innervation and specialized muscle fibers. The SIL appears to be a specialized layer unique to normal humans. The presence of the highly specialized slow-tonic and alpha-cardiac MHC isoforms, together with their absence in human newborns and nonhuman primates, suggests that the specialization of the SIL maybe related to speech and respiration. This specialization may reflect the sustained contraction needed in humans to maintain stiffness of the pharyngeal walls during respiration and to shape the walls for speech articulation. In contrast, the FOL is adapted for rapid movement as seen during swallowing. Senescent humans and patients with IPD are known to be susceptible to dysphagia; and this susceptibility may be related to the observed shift in muscle fiber content.

Fatigue neuromusculaire périnéale

The physiology of urinary continence during stress is complex and the role of passive and active mechanisms remains unclear. Coughing leads to a contraction of urethral rhabdomyosphincter and pelvic floor muscles leading to a positive urethro-vesical gradient and continence. Neuromuscular fatigue can involve all striated muscles, including rhabdomyosphincter, peri-urethral and pelvic floor muscles. This article reviews results of studies assessing perineal muscular fatigue in urinary incontinence.A systematic review of the literature (Medline, Pascal and Embase) with use of the MESH keywords fatigue, stress, urinary incontinence, pelvic floor, urethra, urethral pressure, and muscle.Animal models have shown that the pelvic muscles (iliococcygeus and pubococcygeous) exhibit more neuromuscular fatigue than classical skeletal striated muscles (i.e. soleus muscle). Although the human external urethral sphincter is considered to be a highly fatigue-resistant muscle with its high proportion of slow muscle fibers, repeated coughing seems to lead to decreased urethral pressure in numerous women affected with stress urinary incontinence. In this case, "urethral fatigue" might be a possibility.Although few studies have focused on perineal muscular fatigue, such increased fatigue in pelvic floor muscles may play a role in the pathophysiologic features of stress urinary incontinence in women.

Perineal neuromuscular fatigue

Aim The physiology of urinary continence during stress is complex and the role of passive and active mechanisms remains unclear. Coughing leads to a contraction of urethral rhabdomyosphincter and pelvic floor muscles leading to a positive urethro-vesical gradient and continence. Neuromuscular fatigue can involve all striated muscles, including rhabdomyosphincter, peri-urethral and pelvic floor muscles. This article reviews results of studies assessing perineal muscular fatigue in urinary incontinence. Materials and Methods A systematic review of the literature (Medline, Pascal and Embase) with use of the MESH keywords fatigue, stress, urinary incontinence, pelvic floor, urethra, urethral pressure, and muscle. Results Animal models have shown that the pelvic muscles (iliococcygeus and pubococcygeous) exhibit more neuromuscular fatigue than classical skeletal striated muscles (i.e. soleus muscle). Although the human external urethral sphincter is considered to be a highly fatigue-resistant muscle with its high proportion of slow muscle fibers, repeated coughing seems to lead to decreased urethral pressure in numerous women affected with stress urinary incontinence. In this case, “urethral fatigue” might be a possibility. Conclusions Although few studies have focused on perineal muscular fatigue, such increased fatigue in pelvic floor muscles may play a role in the pathophysiologic features of stress urinary incontinence in women.

Seven skeletal muscles rich in slow muscle fibers may function to sustain neutral position in the rodent hindlimb

Skeletal muscles consist of slow-twitch and fast-twitch muscle fibers, which have distinct physiological and biochemical properties. The muscle fiber composition determines the contractile velocity and fatigability of a particular skeletal muscle. We analyzed the systemic distribution of slow muscle fibers in all rodent skeletal muscles by myosin ATPase staining and found that only seven hindlimb skeletal muscles were extremely rich in slow muscle fibers. These included the mouse piriformis (56.5%), gluteus minimus (35.7%), vastus intermedius (24.7%), quadratus femoris (69.9%), adductor brevis (44.3%), gracilis (24.6%), and soleus muscles (35.1%). In mice, the relative proportion of slow muscle fibers did not exceed 15% in skeletal muscles in other regions. The distribution of slow muscle fibers was well conserved in rats and rabbits. The soleus muscle is an important antigravity muscle in both rodents and humans; therefore, these skeletal muscles rich in slow muscle fibers might play an important role in sustaining neutral alignment of the lower extremity.

The proportions of fiber types in human external urethral sphincter: electrophoretic analysis of myosin

The proportions of fast and slow myosin molecules in external urethral sphincter specimens from ten urodynamically normal male bladder carcinoma patients were estimated from the contents of fast and slow myosin light chains in two-dimensional electrophoretic gels. The percentages of fast and slow myosin molecules ranged from 5.0% to 61.4% with a mean of 35.5% and from 38.6% to 95.0% with a mean of 65.5% respectively. It is therefore concluded that the human external urethral sphincter is composed of both fast and slow muscle fibers as well as other voluntary muscles. The human external urethral sphincter is considered to be a highly fatigue-resistant muscle with a very high proportion of slow muscle fibers. In the cases studied so far, there is a great diversity in the proportions of fast and slow myosin molecules; the reason for this remains unknown.

Differential response of the dog quadriceps muscle to external skeletal fixation of the knee.

The change in muscle fiber size and fiber percentage was studied in three heads of the dog quadriceps following 10 weeks of immobilization using an external skeletal fixator. Muscle biopsy morphometric analysis revealed that muscle fiber atrophy was greatest for the vastus medialis and least for the rectus femoris. The atrophic response for type 1 fibers was, in order from most to least atrophied: VM greater than VL greater than RF, whereas for type 2 fibers the corresponding order was VM = VL greater than RF. An increase in connective tissue was also observed for all muscles. These results are discussed in terms of skeletal muscle architecture, initial fiber-type distribution, and level of use. As a result, predictions are made as to the muscles that are most vulnerable to disuse atrophy, namely the postural muscles that contain a relatively large proportion of slow muscle fibers and cross a single joint. Conversely, those that are least susceptible to atrophy are those that are not used as postural muscles, that cross multiple joints, and that are predominantly composed of fast muscle fibers.