Fiber Hypertrophy Research Articles

A Comparison of Techniques for Estimating and Detecting Changes in Skeletal Muscle Cross-Sectional Area

Muscle biopsy and subsequent histological analysis of muscle fibers is a criterion technique for determining hypertrophy of skeletal muscle in resistance- and endurance-trained individuals. However, due to the training necessary to complete the biopsy, and the invasive nature of the biopsy itself, alternative methods for depicting muscle fiber hypertrophy offer increased ability to gather data discerning skeletal muscle hypertrophy. Furthermore, such procedures require less training and are noninvasive. PURPOSE: This project sought to determine if estimated mid-thigh whole muscle cross-sectional area (CSA) is related to muscle fiber CSA from muscle biopsies. METHODS: Twenty-nine resistance-trained men (age: 21 ± 2 yrs, weight: 83.6 ± 11.0 kg, height: 178.7 ± 8.1 cm) underwent six weeks of total-body resistance training. Muscle biopsies were taken from the Vastus lateralis prior to and following training. Mid-thigh circumference and skinfold measurements (anterior, posterior, medial, and lateral) were used to estimate whole muscle mid-thigh cross-sectional area using the methods of Moritani and deVries. RESULTS: Whole-muscle CSA did not significantly increase from pre- (272.737 ± 37.401 cm) to post-training (277.286 ± 29.474 cm; p = 0.201). Muscle fiber CSA did not significantly increase from pre- (4068 ± 865 μm) to post-training (4221 ± 704 μm; p = 0.368). Additionally, pre muscle fiber CSA did not correlate to pre whole-muscle CSA (r = 0.029, p = 0.882). Also, Muscle fiber CSA percent change did not correlate with whole-muscle CSA percent change (r = -0.064, p = 0.741). CONCLUSION: Estimated whole-muscle CSA and muscle fiber CSA do not appear to correlate well. A lack of a relationship between the changes in these measurements following hypertrophy are puzzling and warrant further study.

Lack of muscle fibre hypertrophy, myonuclear addition, and satellite cell pool expansion with resistance training in 83-94-year-old men and women.

To examine satellite cell and myonuclear content in very old (≥83years) individuals, and the response to heavy resistance training. A group of very old men and women (Old, 83-94years, n=29) was randomized to 12weeks of heavy resistance training or untrained controls. A group of young men who did not resistance train (Young, 19-27years, n=9) were included for comparison. Compared to young men, prior to training the old men had smaller type II fibres (-38%, P<0.001), lower satellite cell content (-52%, P<0.001), smaller myonuclear domain (-30%, P<0.001), and a trend for lower myonuclear content (-13%, P=0.09). Old women were significantly different from old men for these parameters, except for satellite cell content. Resistance training had no effect on these parameters in these old men and women. Fibre-size specific analysis showed strong correlations between fibre size and myonuclei per fibre and between fibre size and myonuclear domain for both fibre types (r=0.94-0.99, P<0.0001). In contrast, muscle fibre perimeter per myonucleus seemed to be constant across the range in fibre size, particularly in type I fibres (r=-0.31, P=0.17). The present data demonstrate that type II fibre size, satellite cell content and myonuclear domain is significantly smaller in very old men compared to young men, while myonuclear content is less affected. These parameters were not improved with heavy resistance training at the most advanced stage of ageing.

Elevated myonuclear density during skeletal muscle hypertrophy in response to training is reversed during detraining.

Myonuclei gained during exercise-induced skeletal muscle hypertrophy may be long-lasting and could facilitate future muscle adaptability after deconditioning, a concept colloquially termed "muscle memory." The evidence for this is limited, mostly due to the lack of a murine exercise-training paradigm that is nonsurgical and reversible. To address this limitation, we developed a novel progressive weighted-wheel-running (PoWeR) model of murine exercise training to test whether myonuclei gained during exercise persist after detraining. We hypothesized that myonuclei acquired during training-induced hypertrophy would remain following loss of muscle mass with detraining. Singly housed female C57BL/6J mice performed 8 wk of PoWeR, while another group performed 8 wk of PoWeR followed by 12 wk of detraining. Age-matched sedentary cage-dwelling mice served as untrained controls. Eight weeks of PoWeR yielded significant plantaris muscle fiber hypertrophy, a shift to a more oxidative phenotype, and greater myonuclear density than untrained mice. After 12 wk of detraining, the plantaris muscle returned to an untrained phenotype with fewer myonuclei. A finding of fewer myonuclei simultaneously with plantaris deconditioning argues against a muscle memory mechanism mediated by elevated myonuclear density in primarily fast-twitch muscle. PoWeR is a novel, practical, and easy-to-deploy approach for eliciting robust hypertrophy in mice, and our findings can inform future research on the mechanisms underlying skeletal muscle adaptive potential and muscle memory.

Type 1 Muscle Fiber Hypertrophy after Blood Flow-restricted Training in Powerlifters.

To investigate the effects of blood flow-restricted resistance exercise (BFRRE) on myofiber areas (MFA), number of myonuclei and satellite cells (SC), muscle size and strength in powerlifters. Seventeen national level powerlifters (25 ± 6 yr [mean ± SD], 15 men) were randomly assigned to either a BFRRE group (n = 9) performing two blocks (weeks 1 and 3) of five BFRRE front squat sessions within a 6.5-wk training period, or a conventional training group (Con; n = 8) performing front squats at 60%-85% of one-repetition maximum (1RM). The BFRRE consisted of four sets (first and last set to voluntary failure) at ~30% of 1RM. Muscle biopsies were obtained from m. vastus lateralis (VL) and analyzed for MFA, myonuclei, SC and capillaries. Cross-sectional areas (CSA) of VL and m. rectus femoris were measured by ultrasonography. Strength was evaluated by maximal voluntary isokinetic torque (MVIT) in knee extension and 1RM in front squat. BFRRE induced selective increases in type I MFA (BFRRE: 12% vs Con: 0%, P < 0.01) and myonuclear number (BFRRE: 18% vs Con: 0%, P = 0.02). Type II MFA was unaltered in both groups. BFRRE induced greater changes in VL CSA (7.7% vs 0.5%, P = 0.04), which correlated with the increases in MFA of type I fibers (r = 0.81, P = 0.02). No group differences were observed in SC and strength changes, although MVIT increased with BFRRE (P = 0.04), whereas 1RM increased in Con (P = 0.02). Two blocks of low-load BFRRE in the front squat exercise resulted in increased quadriceps CSA associated with preferential hypertrophy and myonuclear addition in type 1 fibers of national level powerlifters.

Human skeletal muscle macrophages increase following cycle training and are associated with adaptations that may facilitate growth

Skeletal muscle macrophages participate in repair and regeneration following injury. However, their role in physiological adaptations to exercise is unexplored. We determined whether endurance exercise training (EET) alters macrophage content and characteristics in response to resistance exercise (RE), and whether macrophages are associated with other exercise adaptations. Subjects provided vastus lateralis biopsies before and after one bout of RE, after 12 weeks of EET (cycling), and after a final bout of RE. M2 macrophages (CD11b+/CD206+) did not increase with RE, but increased in response to EET (P < 0.01). Increases in M2 macrophages were positively correlated with fiber hypertrophy (r = 0.49) and satellite cells (r = 0.47). M2c macrophages (CD206+/CD163+) also increased following EET (P < 0.001), and were associated with fiber hypertrophy (r = 0.64). Gene expression was quantified using NanoString. Following EET, the change in M2 macrophages was positively associated with changes in HGF, IGF1, and extracellular matrix genes. EET decreased expression of IL6 (P < 0.05), C/EBPβ (P < 0.01), and MuRF (P < 0.05), and increased expression of IL-4 (P < 0.01), TNFα (P < 0.01) and the TWEAK receptor FN14 (P < 0.05). The change in FN14 gene expression was inversely associated with changes in C/EBPβ (r = −0.58) and MuRF (r = −0.46) following EET. In cultured human myotubes, siRNA inhibition of FN14 increased expression of C/EBPβ (P < 0.05) and MuRF (P < 0.05). Our data suggest that macrophages contribute to the muscle response to EET, potentially including modulation of TWEAK-FN14 signaling.

Role of mTORC1 in mechanically induced increases in translation and skeletal muscle mass.

Skeletal muscle mass is, in part, regulated by the rate of mRNA translation (i.e., protein synthesis). The conserved serine/threonine kinase, mTOR (the mammalian/mechanistic target of rapamycin), found in the multiprotein complex, mTOR complex 1 (mTORC1), is a major positive regulator of protein synthesis. The purpose of this review is to describe some of the critical steps in translation initiation, mTORC1 and its potential direct and indirect roles in regulating translation, and evidence that mTORC1 regulates protein synthesis and muscle mass, with a particular focus on basal conditions and the response to mechanical stimuli. Current evidence suggests that for acute contraction models of mechanical stimuli, there is an emerging pattern suggesting that there is an early increase in protein synthesis governed by a rapamycin-sensitive mTORC1-dependent mechanism, while at later poststimulation time points, the mechanism may change to a rapamycin-insensitive mTORC1-dependent or even an mTORC1-independent mechanism. Furthermore, evidence suggests that mTORC1 appears to be absolutely necessary for muscle fiber hypertrophy induced by chronic mechanical loading but may only play a partial role in the hypertrophy induced by more intermittent types of acute resistance exercise, with the possibility of mTORC1-independent mechanisms also playing a role. Despite the progress that has been made, many questions about the activation of mTORC1, and its downstream targets, remain to be answered. Further research will hopefully provide novel insights into the regulation of skeletal muscle mTORC1 that may eventually be translated into novel exercise programing and/or targeted pharmacological therapies aimed at preventing muscle wasting and/or increasing muscle mass.

Muscle growth mechanisms in response to isoenergetic changes in dietary non-protein energy source at low and high protein levels in juvenile rainbow trout

This study investigates muscle growth mechanisms in juvenile rainbow trout in response to isoenergetic changes in dietary non-protein energy (NPE) source (F, fat vs. C, carbohydrates) at two levels of digestible protein to digestible energy (DP/DE) ratio. Fish (initial weight 32.4 g) were fed four diets having similar DE levels (~18 kJ g−1) with a high (HP/E~26 mg kJ−1) vs. low (LP/E~14 mg kJ−1) DP/DE ratio using F or C as major NPE source (7 week-experiment). The lowering of dietary DP/DE ratio increased myoblast determination protein 1a (myod1a) and decreased myostatin 1b (mstn1b) and cathepsin D (ctsd) muscle mRNA levels. The isoenergetic change in dietary NPE from F to C decreased myod1a and proliferative cell nuclear antigen (pcna) muscle mRNA levels. An interaction between DP/DE ratio and NPE source was observed in muscle transcript levels of myogenic factor 6 (mrf4/myf6), fast myosin heavy chain (fmhc) and fast myosin light chain 2 (fmlc2). White muscle total cross-sectional area decreased at low dietary DP/DE ratio and also when NPE source changed from F to C, linked i) to a decreased total number of white muscle fibres, indicating that low dietary DP/DE restricted muscle hyperplasia and that dietary carbohydrate were less efficiently used than fat to sustain muscle hyperplasia, and ii) to decreased percentage of large muscle fibres, indicating limited fibre hypertrophy. Not only the DP level or the DP/DE ratio, but also the isoenergetic change in dietary NPE source (fat vs carbohydrates) thus appears as a potent regulator of muscle hyperplasia and hypertrophy.

Thirty-day β-hydroxy-βmethylbutyrate supplementation with a controlled diet does not alter the morphological and morphometric characteristics of the rat diaphragm muscle

ABSTRACT Objective To evaluate the β-hydroxy-βmethylbutyrate supplementation influence on the morphological and morphometric characteristics of the diaphragm muscle of rats and verify whether there are sex differences. Methods Experimental study with 48 Wistar rats (24 of each sex) divided into 3 groups: Control Group: in which a daily diet with saline solution was offered; Experimental Group: the same amount of food from the Control group consumed in the previous day and 0.3g/kg of β-hydroxy-βmethylbutyrate; Ad libitum Experimental Group: ad libitum feeding with the same dose of the supplement. The analysis consisted of histomorphometry and classification in diaphragm muscle fiber area bands. The procedures occurred 30 days after the start of the experiment. Data were analyzed using the one-way ANOVA and Tukey tests (p&lt;0.05). Results There was no increase in the cross-sectional area of the diaphragm muscle fibers with the supplementation protocol employed and a similar histological pattern in both sexes. No significant changes were observed in muscle fiber size ranges in the supplemented groups, suggesting that there was no hypertrophy of muscle fibers. Conclusion This study suggests that β-hydroxy-βmethylbutyrate supplementation does not cause changes in the morphological and morphometric characteristics of the diaphragm muscle, regardless of sex.

Amphibious fish 'get a jump' on terrestrial locomotor performance after exercise training on land.

Many amphibious fishes rely on terrestrial locomotion to accomplish essential daily tasks, but it is unknown whether terrestrial exercise improves the locomotor performance of fishes on land. Thus, we tested the hypothesis that terrestrial exercise improves locomotion in amphibious fishes out of water as a result of skeletal muscle remodeling. We compared the jumping performance of Kryptolebias marmoratus before and after an exercise training regimen, and assessed the muscle phenotype of control and exercise-trained fish. We found that exercise-trained fish jumped 41% farther and 48% more times before reaching exhaustion. Furthermore, exercise training resulted in the hypertrophy of red muscle fibers, and an increase in red muscle capillarity and aerobic capacity. Lactate accumulation after jumping indicates that white muscle is also important in powering terrestrial jumps. Overall, skeletal muscle in K. marmoratus is highly responsive to terrestrial exercise, and muscle plasticity may assist in the effective exploitation of terrestrial habitats by amphibious fishes.

Isometric resistance training increases strength and alters histopathology of dystrophin-deficient mouse skeletal muscle.

Mutation to the dystrophin gene causes skeletal muscle weakness in patients with Duchenne muscular dystrophy (DMD) or Becker muscular dystrophy (BMD). Deliberation continues regarding implications of prescribing exercise for these patients. The purpose of this study was to determine whether isometric resistance exercise (~10 tetanic contractions/session) improves skeletal muscle strength and histopathology in the mdx mouse model of DMD. Three isometric training sessions increased in vivo isometric torque (22%) and contractility rates (54%) of anterior crural muscles of mdx mice. Mice expressing a BMD-causing missense mutated dystrophin on the mdx background showed comparable increases in torque (22%), while wild-type mice showed less change (11%). Increases in muscle function occurred within 1 h and peaked 3 days posttraining; however, the adaptation was lost after 7 days unless retrained. Six isometric training sessions over 4 wk caused increased isometric torque (28%) and contractility rates (22-28%), reduced fibrosis, as well as greater uniformity of fiber cross-sectional areas, fewer embryonic myosin heavy-chain-positive fibers, and more satellite cells in tibialis anterior muscle compared with the contralateral untrained muscle. Ex vivo functional analysis of isolated extensor digitorum longus (EDL) muscle from the trained hindlimb revealed greater absolute isometric force, lower passive stiffness, and a lower susceptibility to eccentric contraction-induced force loss compared with untrained EDL muscle. Overall, these data support the concept that exercise training in the form of isometric tetanic contractions can improve contractile function of dystrophin-deficient muscle, indicating a potential role for enhancing muscle strength in patients with DMD and BMD. NEW & NOTEWORTHY We focused on adaptive responses of dystrophin-deficient mouse skeletal muscle to isometric contraction training and report that in the absence of dystrophin (or in the presence of a mutated dystrophin), strength and muscle histopathology are improved. Results suggest that the strength gains are associated with fiber hypertrophy, reduced fibrosis, increased number of satellite cells, and blunted eccentric contraction-induced force loss in vitro. Importantly, there was no indication that the isometric exercise training was deleterious to dystrophin-deficient muscle.

Effects of intermittent hyperbaric exposure on endurance and interval exercise performance in well-trained mice.

What is the central question of this study? Intermittent hyperbaric exposure (1.3 atmospheres absolute with 20.9% O2 ) enhances endurance capacity by facilitating oxidative and glycolytic capacities in skeletal muscle. It remains unclear whether this strategy enhances endurance performance in well-trained individuals. What is the main finding and its importance? Hyperbaric exposure with endurance training enhanced oxidative and glycolytic capacities and protein levels of mitochondrial transcription factorA, dynamin-related protein-1 and heat shock protein70. Hyperbaric exposure with sprint interval training increased the proportion of typeI muscle fibres and promoted capillary growth and muscle fibre hypertrophy. These results may lead to a new strategy for enhancing exercise capacity in well-trained mice. The study was designed to clarify the mechanisms by which hyperbaric exposure (1.3 atmospheres absolute with 20.9% O2 ) improves endurance and interval exercise capacities in highly trained mice. Male mice in the training group were housed in a cage with a wheel activity device for 7weeks from 5weeks old. Voluntary running markedly increased maximal endurance capacity by 6.4-fold. Trained mice were then subjected to either endurance treadmill training (20-32.5mmin-1 ) or sprint interval training (5s run-10s rest, 30-42.5mmin-1 ) with (HypET or HypSIT, respectively) and without (ET or SIT, respectively) 1h hyperbaric exposure for 4weeks. Maximal endurance capacity was significantly increased by HypET and HypSIT, and maximal interval capacity was significantly enhanced by HypSIT. Peroxisome proliferator-activated receptor gamma coactivator 1-alpha expression levels were markedly increased after HypET and HypSIT. Activity levels of 3-hydroxyacyl-CoA-dehydrogenase, citrate synthase and phosphofructokinase in the red gastrocnemius muscle were increased more by HypET than by ET. Protein levels of mitochondrial transcription factorA, dynamin-related protein-1 and heat shock protein70 were increased more by HypET than by ET. The proportion of type I fibres in the soleus muscle was remarkably increased by HypSIT. Capillary-to-fibre ratio values in the white gastrocnemius were increased more by HypSIT than by SIT. These results suggest that hyperbaric exposure has beneficial effects for endurance and interval training to improve exercise capacity in highly trained mice.

Lactate Promotes Myoblast Differentiation and Myotube Hypertrophy via a Pathway Involving MyoD In Vitro and Enhances Muscle Regeneration In Vivo.

Lactate is a metabolic substrate mainly produced in muscles, especially during exercise. Recently, it was reported that lactate affects myoblast differentiation; however, the obtained results are inconsistent and the in vivo effect of lactate remains unclear. Our study thus aimed to evaluate the effects of lactate on myogenic differentiation and its underlying mechanism. The differentiation of C2C12 murine myogenic cells was accelerated in the presence of lactate and, consequently, myotube hypertrophy was achieved. Gene expression analysis of myogenic regulatory factors showed significantly increased myogenic determination protein (MyoD) gene expression in lactate-treated cells compared with that in untreated ones. Moreover, lactate enhanced gene and protein expression of myosin heavy chain (MHC). In particular, lactate increased gene expression of specific MHC isotypes, MHCIIb and IId/x, in a dose-dependent manner. Using a reporter assay, we showed that lactate increased promoter activity of the MHCIIb gene and that a MyoD binding site in the promoter region was necessary for the lactate-induced increase in activity. Finally, peritoneal injection of lactate in mice resulted in enhanced regeneration and fiber hypertrophy in glycerol-induced regenerating muscles. In conclusion, physiologically high lactate concentrations modulated muscle differentiation by regulating MyoD-associated networks, thereby enhancing MHC expression and myotube hypertrophy in vitro and, potentially, in vivo.

Muscle fiber growth in olive flounder, Paralichthys olivaceus: Fiber hyperplasia at a specific body weight period and continuous hypertrophy

The objective of this study was to investigate muscle fiber growth‐related attributes, especially fiber hyperplasia and hypertrophy, and their relation to growth characteristics in olive flounder. After a conditioning period, juvenile olive flounder (214 g of initial body weight) were weighed after 0, 4, 8, 12, and 24 weeks of a feeding trial and were selected based on mean body weight at each period (G1, G2, G3, G4, and G5, respectively). During the 3.0‐fold increase in body weight (363.1–1,071 g, p &lt; 0.001), the fiber area was increased approximately 2.2 times (p &lt; 0.05), and the median area increased from the G1 to G5 groups (p &lt; 0.05). The G3 group exhibited a greater fiber number than the G2 group (p &lt; 0.05) as the G3 group exhibited a higher percentage of smaller fiber and mosaic hyperplasia. In addition, a higher percentage of centered nuclei and deoxyribonucleic acid amount in the G2 group were accompanied by an increase in fiber number in the G3 group. Therefore, the muscle growth of olive flounder was influenced by continued fiber area growth and a significant number increase by mosaic hyperplasia during a specific period (G2 to G3 groups; from 512.7 to 670.3 g).

Cloning, SNP detection, and growth correlation analysis of the 5' flanking regions of two myosin heavy chain-7 genes in Mandarin fish (Siniperca chuatsi).

Myosin heavy chains (MYHs) play important roles in muscle growth and contraction. In fish, MYHs contribute to hyperplasia and hypertrophy of muscle fibers, which can continue into adult life and thus result in indeterminate growth in some species. We previously identified two MYH genes, MYH-7a and MYH-7b, that are differentially expressed in Mandarin fish (Siniperca chuatsi) and appear to function in early growth. However, the regulatory role of their 5' flanking regions is unknown. To examine the effects of single nucleotide polymorphisms (SNPs) in these regions, we used genome walking to amplify their flanking sequences and analyzed the regulatory elements and binding sites. A single SNP locus was found in the flanking sequence of each gene. These SNP loci are located in the conserved glucocorticoid receptor binding region (MYH-7a: G-614A; Allele frequency: G:A = 94.9:5.1; GG (89.76) and AG (10.24) genotypes) and the LIM homeobox domain transcription factor binding sequence (MYH-7b: C-1933A; Allele frequency: C:A = 54.8:45.2; AA (20.82), AC (48.81), and CC (30.37) genotypes). At the G-614A loci, the GG genotype exhibited more superior growth traits (total length, body length, body height, etc.) than the AG genotype, with the exception of caudal peduncle length. Alternatively, at the C-1933A loci, the AC and AA genotypes showed significant differences in all growth traits, except for head length, with AC exhibiting superior traits. The AA and CC genotypes showed significant differences in caudal peduncle length and height, while no differences were observed between the AC and CC genotypes. Thus, these SNPs in the 5' flanking regions of MYH-7a and MYH-7b are correlated with superior growth and can be used for selecting Mandarin fish during breeding.

'Protein Supplementation after Exercise and before Sleep Does Not Further Augment Muscle Mass and Strength Gains during Resistance Exercise Training in Active Older Men

BackgroundThe proposed benefits of protein supplementation on the skeletal muscle adaptive response to resistance exercise training in older adults remain unclear. ObjectiveThe present study assessed whether protein supplementation after exercise and before sleep augments muscle mass and strength gains during resistance exercise training in older individuals. MethodsForty-one older men [mean ± SEM age: 70 ± 1 y; body mass index (kg/m2): 25.3 ± 0.4] completed 12 wk of whole-body resistance exercise training (3 sessions/wk) and were randomly assigned to ingest either protein (21 g protein, 3 g total leucine, 9 g carbohydrate, 3 g fat; n = 21) or an energy-matched placebo (0 g protein, 25 g carbohydrate, 6 g fat; n = 20) after exercise and each night before sleep. Maximal strength was assessed by 1-repetition-maximum (1RM) strength testing, and muscle hypertrophy was assessed at the whole-body (dual-energy X-ray absorptiometry), upper leg (computed tomography scan), and muscle fiber (biopsy) levels. Muscle protein synthesis rates were assessed during week 12 of training with the use of deuterated water (2H2O) administration. ResultsLeg-extension 1RM increased in both groups (placebo: 88 ± 3 to 104 ± 4 kg; protein: 85 ± 3 to 102 ± 4 kg; P < 0.001), with no differences between groups. Quadriceps cross-sectional area (placebo: 67.8 ± 1.7 to 73.5 ± 2.0 cm2; protein: 68.4 ± 1.4 to 72.3 ± 1.4 cm2; P < 0.001) increased in both groups, with no differences between groups. Muscle fiber hypertrophy occurred in type II muscle fibers (placebo: 5486 ± 418 to 6492 ± 429 µm2; protein: 5367 ± 301 to 6259 ± 391 µm2; P < 0.001), with no differences between groups. Muscle protein synthesis rates were 1.62% ± 0.06% and 1.57% ± 0.05%/d in the placebo and protein groups, respectively, with no differences between groups. ConclusionProtein supplementation after exercise and before sleep does not further augment skeletal muscle mass or strength gains during resistance exercise training in active older men. This study was registered at the Netherlands Trial Registry (www.trialregister.nl) as NTR5082.

PO-009 Exercise Adaptation of Skeletal Muscle Fibers: The Role of MicroRNAs

Objective Explore the relationship between exercise adaptation of skeletal muscle fibers and microRNAs.&#x0D; Methods Research related papers.&#x0D; Results endurance training can switch muscle fiber type by promoting microRNAs (miR-208b, miR-499). For example, the conversion from fast Type IIb muscle fibers to slower Type IIx/d muscle fibers, or from Type IIx muscle fibers to Type IIa muscle fibers. Endurance training can also promote the expression of Peroxisome Proliferator Receptor Gamma Coactivator-1α (PGC-1α) and enhance the oxidative potential for slow muscle fibers by inhibiting some microRNAs such as miR-23a. Resistance training can activate insulin-like growth factor-1/phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin/P70 ribosomal protein S6 kinase (IGF-1/PI3K/Akt/mTOR/P70S6K) pathways and promote fast muscle fibers hypertrophy by inhibiting negative microRNAs (miR-1,miR-133,miR-128a) and promoting positive microRNAs (miR-27,miR-29,miR-486).&#x0D; Conclusions MicroRNAs play an important role in the exercise adaptation of skeletal muscle fibers.

Morphological evidence of anabolic action of the drug histochrome in rats

The aim of the investigation was to assess histochrome’s anabolic effect as a consequence of treatment of various doses in rats in conditions of prolonged physical training. Materials and methods . The experiments were performed on the Wistar’s rats. Experimental Group 1 was subcutaneously injected with histochrome in a dose of 1 mg/kg (n = 20) within 10 days, experimental group 2 was treated subcutaneously at a dose of 10 mg/kg (n = 20), and control group 3 received equivolume injections of isotonic sodium chloride (n = 20). Rat musclehypertrophy was induced using the method of forced swimming. A piece ofmuscle was takenfor morphological examination a day after the first and last period of swimming. Hypertrophy of muscle fibers was evaluated by the cross-sectional diameter of muscle fibers, the average quantity of argyrophilic nucleolar organizer region (AgNOR) proteins and the percentage of nuclei with 1, 2, 3 or more AgNOR compared to intact (control) animals. Results. Microscopic morphological examination of M. gastrocnemius registered increase in diameter of muscle fiber by 19,4% (1 mg/kg) and by 60% (10 mg/kg). In the control group of rats an increase in a transverse section of muscle fibers was not found to be statistically significant. The study of biosynthetic nuclei activity of myosimplastus registered increase the AgNOR proteins in both examines groups of animals in comparison the less dynamics in control one. By 10th day of observation the quantity of myosimplastus with two AgNOR increased in a control group of rats by 10%. The maximum AgNOR proteins gained was marked in case of the prolonged use of histochrome in a dose 1 mg/kg. Conclusion. Histochrome enables the increase in dose-dependent biosynthetic processes in skeletal muscles of rats, providing the development of anabolic effect.

CONGENITAL MYOPATHIES: GENERAL AND RYR1: P.44Mutations in the myomaker gene causes Carey-Fineman-Ziter syndrome with muscle fiber hypertrophy

CONGENITAL MYOPATHIES: GENERAL AND RYR1: P.44Mutations in the myomaker gene causes Carey-Fineman-Ziter syndrome with muscle fiber hypertrophy

First familial limb-girdle muscular dystrophy 2L in China

Limb-girdle muscular dystrophy 2L (LGMD2L) is mainly characterized by late adult onset, atrophy of proximal muscles, chronic progressive and asymmetric weakness, accompanied by increased creatine kinase (CK) levels, dystrophic pathological changes and electromyography showing myogenic damage. To date, familial LGMD2L was reported in European countries and had not been reported in China.A careful investigation of the clinical manifestations, muscle performance imaging, biopsy, and target next-generation sequencing (NGS) technology was utilized to identify pathogenic genetic variants in a 4-generation pedigree that includes 6 affected individuals.The results revealed mild-to-moderate hypertrophy of bilateral gastrocnemii and slight weakness and atrophy in the proximal muscles of the lower limbs, with obviously increased serum creatine kinase levels. The symptoms were more serious in the male proband but were also observed in females. Obvious and symmetric atrophy and fat infiltration of posterior segments of the thigh was evident in muscle magnetic resonance imaging (MRI). The pathological changes included a small amount of atrophic and hypertrophic fibers, scattered necrotizing fibers, a small number of increased nuclei, inward migration, mild proliferation of interstitial connective tissue, and no inflammatory cell infiltration. The pathogenic allele was a c.220C > T mutation in the anoctamin 5 (ANO5) gene.The LGMD2L family was characterized by mild chronic myopathy and bilateral gastrocnemius hypertrophy with obviously increased CK levels. Pathological changes included atrophy of fibers with interstitial connective tissues hyperplasia. The pathogenic allele was a c.220C> T mutation in the ANO5 gene.

Carey-Fineman-Ziter syndrome with mutations in the myomaker gene and muscle fiber hypertrophy.

ObjectiveTo describe the long-term clinical follow-up in 3 siblings with Carey-Fineman-Ziter syndrome (CFZS), a form of congenital myopathy with a novel mutation in the myomaker gene (MYMK).MethodsWe performed clinical investigations, repeat muscle biopsy in 2 of the siblings at ages ranging from 11 months to 18 years, and whole-genome sequencing.ResultsAll the siblings had a marked and characteristic facial weakness and variable dysmorphic features affecting the face, hands, and feet, and short stature. They had experienced muscle hypotonia and generalized muscle weakness since early childhood. The muscle biopsies revealed, as the only major abnormality at all ages, a marked hypertrophy of both type 1 and type 2 fibers with more than twice the diameter of that in age-matched controls. Genetic analysis revealed biallelic mutations in the MYMK gene, a novel c.235T>C; p.(Trp79Arg), and the previously described c.271C>A; p.(Pro91Thr).ConclusionsOur study expands the genetic and clinical spectrum of MYMK mutations and CFZS. The marked muscle fiber hypertrophy identified from early childhood, despite apparently normal muscle bulk, indicates that defective fusion of myoblasts during embryonic muscle development results in a reduced number of muscle fibers with compensatory hypertrophy and muscle weakness.