Fiber Hypertrophy Research Articles

Influence of rearing temperature on muscle growth and adipose tissue in Nile tilapia (Oreochromis niloticus) strains

This study aimed to evaluate the effect of temperature on the tissue growth of Red, GIFT and Supreme tilapia strains. Fingerlings of approximately 1.4 g from male populations were reared for a period of 60 days, in three recirculating systems, each system containing 6 water tanks of 0.5 m³, at three temperatures (22, 28 and 30oC). Ten fish of each recirculation system and each temperature studied were sampled. Fishes have been anesthetized, euthanized and weighed. The samplings have been done from the dorsal musculature, caudal, visceral and ventral subcutaneous adipose tissue. Histological sections were prepared and evaluated to determine the diameter of the cells. The experimental design was completely randomized factorial 3 X 3 (strain X temperature). Analysis of variance was performed and means were compared. Higher weights were found for fish reared at 30°C (56.23 g) compared to those grown at 28 (42.12 g) or 22°C (10.52 g). The cooled water temperature (22°C) may have contributed to the hypertrophy of white muscle fibers and visceral adipocytes from tilapia, compared to 28 or 30oC. Red Tilapia, GIFT and Supreme strains show differences in muscle growth and adipose tissues in response to temperature of cultivation.

Computational modeling of the electromechanical response of a ventricular fiber affected by eccentric hypertrophy

Abstract The aim of this work is to study the effects of eccentric hypertrophy on the electromechanics of a single myocardial ventricular fiber by means of a one-dimensional finite-element strongly-coupled model. The electrical current ow model is written in the reference configuration and it is characterized by two geometric feedbacks, i.e. the conduction and convection ones, and by the mechanoelectric feedback due to stretchactivated channels. First, the influence of such feedbacks is investigated for both a healthy and a hypertrophic fiber in case of isometric simulations. No relevant discrepancies are found when disregarding one or more feedbacks for both fibers. Then, all feedbacks are taken into account while studying the electromechanical responses of fibers. The results from isometric tests do not point out any notable difference between the healthy and hypertrophic fibers as regards the action potential duration and conduction velocity. The length-tension relationships show increased stretches and reduced peak values for tension instead. The tension-velocity relationships derived from afterloaded isotonic and quick- release tests depict higher values of contraction velocity at smaller afterloads. Moreover, higher maximum shortenings are achieved during the isotonic contraction. In conclusion, our simulation results are innovative in predicting the electromechanical behavior of eccentric hypertrophic fibers.

Exercise-Induced Hypertrophic and Oxidative Signaling Pathways and Myokine Expression in Fast Muscle of Adult Zebrafish

Skeletal muscle is a plastic tissue that undergoes cellular and metabolic adaptations under conditions of increased contractile activity such as exercise. Using adult zebrafish as an exercise model, we previously demonstrated that swimming training stimulates hypertrophy and vascularization of fast muscle fibers, consistent with the known muscle growth-promoting effects of exercise and with the resulting increased aerobic capacity of this tissue. Here we investigated the potential involvement of factors and signaling mechanisms that could be responsible for exercise-induced fast muscle remodeling in adult zebrafish. By subjecting zebrafish to swimming-induced exercise, we observed an increase in the activity of mammalian target of rapamycin (mTOR) and Mef2 protein levels in fast muscle. We also observed an increase in the protein levels of the mitotic marker phosphorylated histone H3 that correlated with an increase in the protein expression levels of Pax7, a satellite-like cell marker. Furthermore, the activity of AMP-activated protein kinase (AMPK) was also increased by exercise, in parallel with an increase in the mRNA expression levels of pgc1α and also of pparda, a β-oxidation marker. Changes in the mRNA expression levels of slow and fast myosin markers further supported the notion of an exercise-induced aerobic phenotype in zebrafish fast muscle. The mRNA expression levels of il6, il6r, apln, aplnra and aplnrb, sparc, decorin and igf1, myokines known in mammals to be produced in response to exercise and to signal through mTOR/AMPK pathways, among others, were increased in fast muscle of exercised zebrafish. These results support the notion that exercise increases skeletal muscle growth and myogenesis in adult zebrafish through the coordinated activation of the mTOR-MEF2 and AMPK-PGC1α signaling pathways. These results, coupled with altered expression of markers for oxidative metabolism and fast-to-slow fiber-type switch, also suggest improved aerobic capacity as a result of swimming-induced exercise. Finally, the induction of myokine expression by swimming-induced exercise support the hypothesis that these myokines may have been produced and secreted by the exercised zebrafish muscle and acted on fast muscle cells to promote metabolic remodeling. These results support the use of zebrafish as a suitable model for studies on muscle remodeling in vertebrates, including humans.

Host gut-derived probiotic bacteria promote hypertrophic muscle progression and upregulate growth-related gene expression of slow-growing Malaysian Mahseer Tor tambroides

In modern aquaculture, dietary supplementation of probiotics is a novel approach for enhancing growth performance of slow-growing fish. However, the actual role of probiotics in regulating muscle growth at cellular and molecular levels in fish still needs to be clarified. In this study, we hypothesized that host gut derived probiotic bacteria would enhance cellular muscle growth, and upregulate growth-related gene expression in slow-growing Malaysian mahseer Tor tambroides. Therefore, three host-associated probiotics (Bacillus sp. AHG22, Alcaligenes sp. AFG22, and Shewanella sp. AFG21) were isolated from the gastro-intestinal tract of T. tambroides and screened based on their digestive enzyme activity. A fishmeal and casein based control diet (40% crude protein and 10% lipid) was formulated, and three different probiotic supplemented diets were prepared by immersing the control diet in each isolated host-derived bacteria, suspended in sterile phosphate buffered saline (PBS), to achieve a final concentration of approximately 1.0 × 108 CFU g−1 feed. Triplicate groups of T. tambroides juveniles (initial weight 1.39 ± 0.06 g) were stocked in twelve glass aquaria (100 L capacity) with stocking density of 20 individuals per aquarium. The feed was applied twice daily at 3.0% of the fish body weight per day for 90 days. Growth performance (weight gain and specific growth rate) of T. tambroides juveniles were significantly higher in Alcaligenes sp. AFG22 and Bacillus sp. AHG22 supplemented diet treatments. Muscle morphometric analysis revealed that dietary supplementation of host-associated probiotic bacteria did not influence the frequency distribution of hyperplastic (class 10) small diameter fibers (≤10 μm). However, hypertrophic (Class 50, Class 60 and Class 70) large diameter fibers (>50 μm) were significantly higher in Alcaligenes sp. AFG22 and Bacillus sp. AHG22 supplemented treatments, indicating that increased growth rate of T. tambroides in these treatments was mostly governed by increased muscle fibers hypertrophy, rather than by hyperplasia. Real-time PCR data demonstrated that the relative mRNA expression of GH and IGF1 was upregulated in juvenile T. tambroides fed the diets supplemented with Alcaligenes sp. AFG22 and Bacillus sp. AHG22. These results indicate that host-derived probiotics, especially Alcaligenes sp. AFG22 and Bacillus sp. AHG22, have a significant potential as autochthonous probiotics for the stimulation of growth performance of slow-growing T. tambroides in aquaculture.

Differential impact of tongue exercise on intrinsic lingual muscles.

Aging is associated with muscle fiber hypotrophy and decreased percentages of rapidly contracting myosin heavy chain (MyHC) type IIb muscle fibers. Tongue exercise programs used to treat dysphagia target age-related decline in tongue muscle function, but the impact of exercise on the intrinsic tongue muscles is unknown. We hypothesized that exercise would induce muscle fiber hypertrophy and increase the percentage of MyHC IIa fibers in the intrinsic tongue. Animal model. Eight old and eight young-adult rats underwent 8 weeks of tongue exercise training, and 8 animals of each age group served as controls. Longitudinal, transverse, and verticalis muscle samples from the anterior, middle, and posterior regions of the tongue were sectioned and stained to determine muscle fiber diameter and MyHC composition. MyHC fiber type distribution was altered by exercise, and the effects differed by muscle and region of the tongue. In the exercise groups, as compared to the control groups, the anterior transverse and middle superior longitudinal muscles had significantly reduced percentages of MyHC IIx positive fibers and higher percentages of rapidly contracting fatigable MyHC IIb positive muscle fibers, whereas the middle transverse and posterior longitudinal muscles had increased percentages of the less rapidly contracting and more fatigue-resistant MyHC IIa fibers. The impact of exercise did not differ with age, as there was no significant interaction between age and exercise. Tongue exercise had no significant effect on muscle fiber diameter. The impact of exercise varied among the tongue muscles, which may indicate different functional contributions to the tongue exercise task. NA Laryngoscope, 128:2245-2251, 2018.

DGKζ deficiency protects against peripheral insulin resistance and improves energy metabolism

Diacylglycerol kinases (DGKs) regulate the balance between diacylglycerol (DAG) and phosphatidic acid. DGKζ is highly abundant in skeletal muscle and induces fiber hypertrophy. We hypothesized that DGKζ influences functional and metabolic adaptations in skeletal muscle and whole-body fuel utilization. DAG content was increased in skeletal muscle and adipose tissue, but unaltered in liver of DGKζ KO mice. Linear growth, body weight, fat mass, and lean mass were reduced in DGKζ KO versus wild-type mice. Conversely, male DGKζ KO and wild-type mice displayed a similar robust increase in plantaris weight after functional overload, suggesting that DGKζ is dispensable for muscle hypertrophy. Although glucose tolerance was similar, insulin levels were reduced in high-fat diet (HFD)-fed DGKζ KO versus wild-type mice. Submaximal insulin-stimulated glucose transport and p-Akt Ser473 were increased, suggesting enhanced skeletal muscle insulin sensitivity. Energy homeostasis was altered in DGKζ KO mice, as evidenced by an elevated respiratory exchange ratio, independent of altered physical activity or food intake. In conclusion, DGKζ deficiency increases tissue DAG content and leads to modest growth retardation, reduced adiposity, and protection against insulin resistance. DGKζ plays a role in the control of growth and metabolic processes, further highlighting specialized functions of DGK isoforms in type 2 diabetes pathophysiology.

Trimetazidine restores the positive adaptation to exercise training by mitigating statin-induced skeletal muscle injury.

BackgroundExercise rehabilitation is demonstrated to improve the prognosis of patients with coronary heart disease (CHD). Statins, as the key medicine to lower cholesterol in CHD, result in skeletal muscle injury and impair exercise training adaptation. Energy metabolism dysfunction is identified as the potential mechanism underlying statin‐induced skeletal muscle injury. In this study, we investigated the effects of the metabolic modulator trimetazidine on skeletal muscle energy metabolism and statin‐associated exercise intolerance.MethodsHigh‐fat fed apolipoprotein E knockout (ApoE−/−) mice were given aerobic exercise and administrated simvastatin, trimetazidine, or simvastatin plus trimetazidine by gavage. Exercise capacity was evaluated at the end of the treatment by hanging grid test, forelimb grip strength, and running tolerance test. Plasma glucose, lipid, and creatine kinase concentrations were measured at the end of the treatment. After sacrifice, gastrocnemii were stored for assessment of muscle morphology and fibre type. Energy metabolism was estimated by plasma lactic acid concentration, ragged red fibres, and glycogen stores. Activities of mitochondrial complex III, citrate synthase activity, and membrane potential were measured to assess mitochondrial function. Oxidative stress was also evaluated by superoxide in mitochondria, superoxide dismutase activity, and glutathione redox state.ResultsIn high‐fat fed ApoE−/− mice, exercise training had no effect on lipid concentrations. Lower lipid concentrations with increased creatine kinase were observed with additional simvastatin treatment. Exercise capacity increased significantly in response to exercise training alone but was blunted by the addition of simvastatin. Similarly, cross‐sectional area of muscle fibres and the proportion of slow‐twitch fibres increased in the exercise group but decreased in the simvastatin plus exercise group. Additionally, simvastatin increased centronucleated fibres and induced energy metabolism dysfunction by inhibiting complex III activity and thus promoted oxidative stress in gastrocnemius. We demonstrated that trimetazidine could reverse simvastatin‐induced exercise intolerance and muscle damages. We also found the ability of trimetazidine in restoration of muscle fibre hypertrophy and facilitating fast‐to‐slow type shift. The energy metabolism dysfunction and oxidative stress in gastrocnemii were rescued by trimetazidine.ConclusionsTrimetazidine alleviated statin‐related skeletal muscle injury by restoration of oxidative phenotype and increasing fibre cross‐sectional areas in response to exercise training. Correspondingly, the exercise training adaptation were improved in high‐fat fed ApoE−/− mice. Moreover, trimetazidine is able to exert its positive effects without affecting the beneficial lipid‐lowering properties of the statins. Thus, trimetazidine could be prescribed to remedy the undesirable statins‐induced exercise intolerance during cardiac rehabilitation in patients with CHD.

Effect of dietary methionine level on muscle growth mechanisms in juvenile rainbow trout (Oncorhynchus mykiss)

The aim of the study was to analyse the effects of different dietary methionine (Met) concentrations on the mechanisms of fish muscle growth (hyperplasia and hypertrophy) by using cellular and molecular approaches. Three plant-based diets differing by their Met level (MD, Met-deficient; MC, Met-control, corresponding to established Met requirement; MH, Met-high) were fed to rainbow trout juveniles for 12weeks. Met deficiency led to a reduced somatic growth right from the first 3weeks of feeding onwards, while feeding the MH-diet led to an increased body growth in the 6 last weeks of feeding. The protein gain of the juveniles increased with dietary Met content. The protein retention efficiency of the MD-fed juveniles was half that of the MC- and MH-fed juveniles which were statistically similar. The changes induced by MD- and MH-feeding at muscle molecular and cellular levels were different. Compared to control, dietary Met deficiency altered the expression of myogenic, muscle growth- and metabolism-related genes by increasing Myf5, MyoD1, Mrf4, Mef2a, βact, CathD, GSTπ and TNFα expressions and decreasing Col1α1 and IGF1 expressions, whereas a high level of dietary Met decreased Pax7a2, Mef2c, βact, CathD, GDH2 and NF-κB expressions. The Met-control fed fish were discrimated according to HGF, Pax7a1 and Pax7a2 expressions. Dietary Met level thus acted on the expression of genes regulating specific transition points of myogenesis, and affected the expression of muscle structural genes and growth factors involved in satellite cell activation and muscle growth. Molecular results suggested that MD-diet favours satellite cell return to quiescence, while MC-diet favours satellite cell activation and MH-diet myogenic differentiation. At cellular level, the muscle total cross-sectional area of the juveniles fed the MD-diet was 28% lower than that of the juveniles fed the MC-diet despite a similar total number of white muscle fibres, and the number of white muscle fibres with a large diameter was lower in MD-fed fish than in MC-fed ones. The muscle total cross-sectional area of the juveniles fed the MH-diet was 32% higher than that of the juveniles fed the MC-diet, their total number of white muscle fibres 25% higher, and their number of white muscle fibres with a large diameter similar. Increasing dietary methionine above established requirement thus promotes white muscle hyperplasia and muscle growth in rainbow trout juveniles, while methionine deficiency dysregulates the expression of myogenic and muscle growth-related genes and impairs white fibre hypertrophy. Statement of relevanceDetermining the effects of dietary methionine levels on muscle growth mechanisms will help develop low fish meal feeds.

Exercise Training Reveals Inflexibility of the Diaphragm in an Animal Model of Patients With Obesity-Driven Heart Failure With a Preserved Ejection Fraction.

BackgroundRespiratory muscle weakness contributes to exercise intolerance in patients with heart failure with a preserved ejection fraction (HFpEF)—a condition characterized by multiple comorbidities with few proven treatments. We aimed, therefore, to provide novel insight into the underlying diaphragmatic alterations that occur in HFpEF by using an obese cardiometabolic rat model and further assessed whether exercise training performed only after the development of overt HFpEF could reverse impairments.Methods and ResultsObese ZSF1 rats (n=12) were compared with their lean controls (n=8) at 20 weeks, with 3 additional groups of obese ZSF1 rats compared at 28 weeks following 8 weeks of either sedentary behavior (n=13), high‐intensity interval training (n=11), or moderate‐continuous training (n=11). Obese rats developed an obvious HFpEF phenotype at 20 and 28 weeks. In the diaphragm at 20 weeks, HFpEF induced a shift towards an oxidative phenotype and a fiber hypertrophy paralleled by a lower protein expression in MuRF1 and MuRF2, yet mitochondrial and contractile functional impairments were observed. At 28 weeks, neither the exercise training regimen of high‐intensity interval training or moderate‐continuous training reversed any of the diaphragm alterations induced by HFpEF.ConclusionsThis study, using a well‐characterized rat model of HFpEF underpinned by multiple comorbidities and exercise intolerance (ie, one that closely resembles the patient phenotype), provides evidence that diaphragm alterations and dysfunction induced in overt HFpEF are not reversed following 8 weeks of aerobic exercise training. As such, whether alternative therapeutic interventions are required to treat respiratory muscle weakness in HFpEF warrants further investigation.

P.295 - C-terminal binding protein 1 (CtBP1) deficiency, mimicking congenital myopathy during infancy

The CtBP1 gene was identified as transcriptional co-repressor that modulates gene expression in multiple cellular pathways. CtBP1 plays a critical role during human embryogenic period. CtBP1 gene presents an active role in myogenesis and post synaptic membrane receptor formation. Its has been associated recently with human disease. Hypotony and muscle weakness are two of the most relevant clinical features, however its effects in muscle pathology has not been described enough . Herein, we describe the fifth reported patient, who showed a similar phenotype of former described patients, sharing the same mutation. Currently is 8 year- old girl born from a non-consanguineous parent. Because her early hypotonia, motor development delay and myogenic EMGs patterns, congenital myopathy was suspected. Muscle biopsy performed at 3 years old showed, atrophic and hypertrophic fibers with abnormal intermyofibrillar network in several fibers. Electron microscope revealed disruption of sarcomeres with Z-line streaming, Intermyofibrillar neatwork disruption and absence of mitochondria. These features extended from 1 to 4–5 sarcomeres. At that time, truncal ataxia was noticed evolving to a progressive cerebellar syndrome, losing their motor and cognitive acquired abilities and developing a severe scoliosis. Tooth enamel defects were also observed. Exome sequencing studies confirmed a heterozygous p.R331W mutation in CtBP1 gene, previously reported and affecting all the former described patients. Segregation analysis did not show this variant in neither of the parents in her brother. Mutation in CtBP1 may be considered as a congenital regressive and severe condition affecting several organs. Because hypotonia is one of the main and first clinical symptoms, CTBP1 deficiency must be added to causes of floppy infant syndrome.

P.476 - Muscle hyperthrophy with RYR1 mutation

We report 4 members of the same family with muscle hypertrophy and cramps. They all presented with hip dysplasia at birth and rapidly developed significant muscle hypertrophy in infancy with unusual strength. The older members later developed refractory cramps despite Dantrolene. Some presented spontaneous rhabdomyolysis and heat intolerance during summer. Non dystrophic myotonias genes were tested and came back negative They were all found with an autosomal dominant known RYR1 mutation (p.Arg4737Trp). Muscle biopsy demonstrated absence of cores and only mid hypertrophic fibres. To our knowledge only one family with muscle hypertrophy and RYR1 mutation has been reported. We are investigating to see if this new phenotype is really only due to RYR mutation or a second hit in the excitation coupling contraction system. Whole exome sequencing is still pending as well as functional analysis to see the real impact of this mutation on Ryanodine channel to explain the phenotype. These cases are interesting to show the major role of RYR1 on muscle size and power potentially opening new ways for treatment of congenital myopathies.

Dietary amino acid profile affects muscle cellularity, growth, survival and ammonia excretion of meagre (Argyrosomus regius)larvae

Formulation of diets according to fish amino acid (AA) qualitative requirements may improve fish growth. Two diets with different AA profiles were tested on 16-day-old meagre during 20 days. The first diet had an AA profile closer to meagre larval AA requirements (BAL), whereas the second had a different AA profile (UNBAL). Results showed that larvae fed the diet with higher similarities to the AA profile of meagre carcass had a higher final weight (19.8 ± 0.5 mg versus 13.4 ± 1.8 mg) and lower ammonia excretion after being fed (0.6 ± 0.1 ml/(g DW. larvae. h) and 0.8 ± 0.1 ml/(g DW larvae. h)). A higher mean fibre area was obtained in 36 DAH larvae fed the BAL diet (224.8 ± 33.3 μm2 versus 158.8 ± 34.5 μm2) as well as higher larval weight. When fibre area distribution was analysed, a higher frequency of larger fibres was observed in 36 DAH BAL larvae, suggesting that fibre hypertrophy had a higher importance in this treatment. In conclusion, this study shows that meagre larvae fed a diet with an AA profile closer to their requirements had lower nitrogen losses and higher final weight, as result of higher muscle hypertrophy.

Fiber-type distribution and expression of myosin heavy chain isoforms in newborn heterozygous myostatin-knockout pigs.

To explore the effects of heterozygous myostatin-knockout (MSNT+/-) on muscle characteristics, specifically fiber-type distribution and expression of myosin heavy chain isoforms in pigs. The fiber cross-sectional area of the semitendinosus and semimembranosus muscles were much larger in MSTN+/- pigs at birth than in wild-type (WT) pigs. MSTN+/- pigs had a higher proportion of fast-type fibers and lower succinate dehydrogenase activity in muscles than WT pigs. The myosin heavy chain IIB mRNA level in both two muscles was~threefold higher in MSTN+/- pigs compared with WT pigs. MSTN+/- pigs exhibit a disproportionate increase in muscle mass and can have a higher body weight due to fiber hypertrophy, a change in the fiber-type distribution, and alteration of myosin heavy chain isoforms levels, leading to more fast glycolytic fibers.

Differential requirement for satellite cells during overload-induced muscle hypertrophy in growing versus mature mice

BackgroundPax7+ satellite cells are required for skeletal muscle fiber growth during post-natal development in mice. Satellite cell-mediated myonuclear accretion also appears to persist into early adulthood. Given the important role of satellite cells during muscle development, we hypothesized that the necessity of satellite cells for adaptation to an imposed hypertrophic stimulus depends on maturational age.MethodsPax7CreER-R26RDTA mice were treated for 5 days with vehicle (satellite cell-replete, SC+) or tamoxifen (satellite cell-depleted, SC-) at 2 months (young) and 4 months (mature) of age. Following a 2-week washout, mice were subjected to sham surgery or 10 day synergist ablation overload of the plantaris (n = 6–9 per group). The surgical approach minimized regeneration, de novo fiber formation, and fiber splitting while promoting muscle fiber growth. Satellite cell density (Pax7+ cells/fiber), embryonic myosin heavy chain expression (eMyHC), and muscle fiber cross sectional area (CSA) were evaluated via immunohistochemistry. Myonuclei (myonuclei/100 mm) were counted on isolated single muscle fibers.ResultsTamoxifen treatment depleted satellite cells by ≥90% and prevented myonuclear accretion with overload in young and mature mice (p < 0.05). Satellite cells did not recover in SC- mice after overload. Average muscle fiber CSA increased ~20% in young SC+ (p = 0.07), mature SC+ (p < 0.05), and mature SC- mice (p < 0.05). In contrast, muscle fiber hypertrophy was prevented in young SC- mice. Muscle fiber number increased only in mature mice after overload (p < 0.05), and eMyHC expression was variable, specifically in mature SC+ mice.ConclusionsReliance on satellite cells for overload-induced hypertrophy is dependent on maturational age, and global responses to overload differ in young versus mature mice.

Muscle hypertrophy in prediabetic men after 16 wk of resistance training

Resistance training of healthy young men typically results in muscle hypertrophy and a shift in vastus lateralis composition away from type IIx fibers to an increase in IIa fiber content. Our previous studies of 8 wk of resistance training found that many metabolic syndrome men and women paradoxically increased IIx fibers with a decrease in IIa fibers. To confirm the hypothesis that obese subjects might have muscle remodeling after resistance training very different from healthy lean subjects, we subjected a group of nine obese male volunteers to progressive resistance training for a total of 16 wk. In these studies, weight loss was discouraged so that muscle changes would be attributed to the training alone. Detailed assessments included comparisons of histological examinations of needle biopsies of vastus lateralis muscle pretraining and at 8 and 16 wk. Prolonging the training from 8 to 16 wk resulted in increased strength, improved body composition, and more muscle fiber hypertrophy, but euglycemic clamp-quantified insulin responsiveness did not improve. Similar to prior studies, muscle fiber composition shifted toward more fast-twitch type IIx fibers (23 to 42%). Eight weeks of resistance training increased the muscle expression of phosphorylated Akt2 and mTOR. Muscle GLUT4 expression increased, although insulin receptor and IRS-1 expression did not change. We conclude that resistance training of prediabetic obese subjects is effective at changing muscle, resulting in fiber hypertrophy and increased type IIx fiber content, and these changes continue up to 16 wk of training.NEW & NOTEWORTHY Obese, insulin-resistant men responded to 16 wk of progressive resistance training with muscle hypertrophy and increased strength and a shift in muscle fiber composition toward fast-twitch, type IIx fibers. Activation of muscle mTOR was increased by 8 wk but did not increase further at 16 wk despite continued augmentation of peak power and rate of force generation.

Regulation of turkey myogenic satellite cell migration by MicroRNAs miR-128 and miR-24

Myogenic satellite cells are an adult stem cell responsible for all post-hatch muscle growth in poultry. As a stem cell population, satellite cells are highly heterogeneous, but the origin of this heterogeneity remains unclear. Heterogeneity is, in part, regulated by gene expression. One method of endogenous gene regulation that may contribute to heterogeneity is microRNAs (miRNAs). Two miRNAs previously shown to regulate poultry myogenic satellite cell proliferation and differentiation, miR-128 and miR-24, were studied to determine if they also affected satellite cell migration. Satellite cell migration is an essential step for both proliferation and differentiation. During proliferation, satellite cells will migrate and align to form new myofibers or donate their nuclei to existing myofibers leading to muscle fiber hypertrophy or regeneration. Transient transfection of miRNA specific mimics to each miRNA reduced migration of satellite cells following a cell culture scratch at 72 h of proliferation when the cultures were 90 to 100% confluent. However, only the migration in cells transfected with miR-24 mimics at 24 and 30 h following the scratch was significantly reduced (P ≤ 0.05) to around 70% of the distance migrated by controls. Alternately, transfection with inhibitors specific to miR-128 or miR-24 significantly (P ≤ 0.05) increased migration between 147 and 252% compared to their controls between 24 and 48 h following the scratch. These data demonstrate that miR-128 and miR-24 play a role in myogenic satellite cell migration, which will impact muscle development and growth.

Molecular Regulation of Exercise-Induced Muscle Fiber Hypertrophy.

Skeletal muscle hypertrophy is a widely sought exercise adaptation to counteract the muscle atrophy of aging and disease, or to improve athletic performance. While this desired muscle enlargement is a well-known adaptation to resistance exercise training (RT), the mechanistic underpinnings are not fully understood. The purpose of this review is thus to provide the reader with a summary of recent advances in molecular mechanisms-based on the most current literature-that are thought to promote RT-induced muscle hypertrophy. We have therefore focused this discussion on the following areas of fertile investigation: ribosomal function and biogenesis, muscle stem (satellite) cell activity, transcriptional regulation, mechanotransduction, and myokine signaling.

Motor neuron scaling and somatic growth in normal and transgenic rainbow trout, Oncorhynchus mykiss

Teleost fishes demonstrate indeterminate growth and a dramatic increase in body mass over their life cycle. Myotonal muscle mass comprises &gt;60% of the adult body mass in active species and effective growth and development of functional capability requires interactions between multuinucleated muscle fibers (myocytes) and motor neurons. Basically, as all organisms grow and develops, the nervous system must compensate for the change in size. While numerous studies have examined myogenesis, muscle fiber recruitment and hypertrophy, and phenotypic plasticity in fishes, our understanding of the myocyte/neuron linkage during development is extremely limited. The goal of this project is to determine how motor neurons in rainbow trout change through development and how this change can be viewed through principles of scaling. Sections of spinal cord were removed at the rostral, medial, and caudal positions from normal and genetically modified rainbow trout to overexpress follistatin, which antagonizes myostatin and increases myotonal muscle. Increased muscling in these transgenic trout is due primarily to myocyte hyperplasia. Spinal cords (n= 35) were sectioned on a microtome and stained with acridine orange. Sections were analyzed to 1) measure the cross sectional area of the spinal cord and ventral horn motor neurons and 2) determine how motor neurons develop to compensate for growth in total muscle mass. The average motor neuron area from normal rainbow trout revealed an unusual allometric relationship compared to endothermic animals. As the mass of the fish increased there was a positive (r2 = 0.961) correlation to the motor neuron area. Compared with normal rainbow trout, transgenic trout had an average neuron area similar to that of the normal trout, but relative to per gram of body mass motor neuron is significantly less, suggesting that the motor unit size – the number of skeletal muscle fibers per motor neuron ‐ increases with an increase in muscle mass. Previous studies suggest that neuron size in endothermic organisms follow a pattern of metabolic allometric scaling, yet motor neuron from ectotherms in this study had scaling coefficient of just 0.204. These findings suggest that as the axial muscle increases mass in normal and transgenic rainbow trout, the peripheral nervous system is not undergoing a similar growth in neuron size.Support or Funding InformationNIH Grant #P20 RR0116454

Protein Supplementation Augments Muscle Fiber Hypertrophy but Does Not Modulate Satellite Cell Content During Prolonged Resistance-Type Exercise Training in Frail Elderly

ObjectiveProtein supplementation increases gains in lean body mass following prolonged resistance-type exercise training in frail older adults. We assessed whether the greater increase in lean body mass can be attributed to muscle fiber type specific hypertrophy with concomitant changes in satellite cell (SC) content. DesignA total of 34 frail elderly individuals (77 ± 1 years, n = 12 male adults) participated in this randomized, double-blind, placebo-controlled trial with 2 arms in parallel. InterventionParticipants performed 24 weeks of progressive resistance-type exercise training (2 sessions per week) during which they were supplemented twice-daily with milk protein (2 × 15 g) or a placebo. MethodsMuscle biopsies were taken at baseline, and after 12 and 24 weeks of intervention, to determine type I and type II muscle fiber specific cross-sectional area (CSA), SC content, and myocellular characteristics. ResultsIn the placebo group, a trend for a 20% ± 11% increase in muscle fiber CSA was observed in type II fibers only (P = .051), with no increase in type I muscle fiber CSA. In the protein group, type I and II muscle fiber CSA increased by 23% ± 7% and 34% ± 10% following 6 months of training, respectively (P < .01). Myonuclear domain size increased over time in both groups and fiber types (P < .001), with no significant differences between groups (P > .05). No changes in myonuclear content and SC contents were observed over time in either group (both P > .05). Regression analysis showed that changes in myonuclear content and domain size are predictive of muscle fiber hypertrophy. ConclusionsProtein supplementation augments muscle fiber hypertrophy following prolonged resistance-type exercise training in frail older people, without changes in myonuclear and SC content.

Misregulation of calcium-handling proteins promotes hyperactivation of calcineurin-NFAT signaling in skeletal muscle of DM1 mice.

Myotonic Dystrophy type 1 (DM1) is caused by an expansion of CUG repeats in DMPK mRNAs. This mutation affects alternative splicing through misregulation of RNA-binding proteins. Amongst pre-mRNAs that are mis-spliced, several code for proteins involved in calcium homeostasis suggesting that calcium-handling and signaling are perturbed in DM1. Here, we analyzed expression of such proteins in DM1 mouse muscle. We found that the levels of several sarcoplasmic reticulum proteins (SERCA1, sarcolipin and calsequestrin) are altered, likely contributing to an imbalance in calcium homeostasis. We also observed that calcineurin (CnA) signaling is hyperactivated in DM1 muscle. Indeed, CnA expression and phosphatase activity are both markedly increased in DM1 muscle. Coherent with this, we found that activators of the CnA pathway (MLP, FHL1) are also elevated. Consequently, NFATc1 expression is increased in DM1 muscle and becomes relocalized to myonuclei, together with an up-regulation of its transcriptional targets (RCAN1.4 and myoglobin). Accordingly, DM1 mouse muscles display an increase in oxidative metabolism and fiber hypertrophy. To determine the functional consequences of this CnA hyperactivation, we administered cyclosporine A, an inhibitor of CnA, to DM1 mice. Muscles of treated DM1 mice showed an increase in CUGBP1 levels, and an exacerbation of key alternative splicing events associated with DM1. Finally, inhibition of CnA in cultured human DM1 myoblasts also resulted in a splicing exacerbation of the insulin receptor. Together, these findings show for the first time that calcium-CnA signaling is hyperactivated in DM1 muscle and that such hyperactivation represents a beneficial compensatory adaptation to the disease.