Myostatin mRNA Expression Research Articles

Dietary arginine requirement in diets of GIFT strain of Nile tilapia, Oreochromis niloticus : Effects on growth performance, whole‐body composition, growth‐related gene expression and haemato‐biochemical responses

This study aims to evaluate the effects of dietary arginine supplementation on growth performances, whole-body composition, haemato-biochemical responses and growth-related gene expression in juvenile GIFT tilapia. Five corn-soy-based isonitrogenous (322 g/kg) and isoenergetic (17.4 MJ/kg) diets were formulated to contain graded levels of dietary arginine (14.7, 15.5, 16.4, 17.6 and 18.5 g/kg of diet). Each diet was randomly assigned to triplicate groups of 30 fish (4.4 ± 0.2 g) per experimental unit, which were fed thrice a day (09:00, 13:00 and 17:00 h) for 60 days. Growth performances and feed utilization were improved in fish fed arginine at 16.4 g/kg of diet compared with other dietary treatments. No significant differences were observed in the whole-body proximate composition, amino acid profile and haematological responses of fish fed graded levels of dietary arginine. However, significant interactions were observed in the blood biochemical responses and mRNA expression of MyoD, Myogenin, GH, IGF-1, GHR-1 and Pax7 in fish fed diets with graded levels of arginine, while dietary arginine levels had no effect on the mRNA expression of myostatin and IGF-2. Second-order polynomial regression analysis of weight gain and nitrogen gain against dietary arginine levels indicated that the optimum dietary arginine requirement for maximum growth and feed utilization of juvenile GIFT tilapia was estimated to be 16.7–16.8 g/kg of diet or 51.8–52.2 g/kg of protein.

Functional and molecular adaptations of quadriceps and hamstring muscles to blood flow restricted training in patients with ACL rupture.

Effects of low-load blood flow restricted (LL-BFR) training remain unexplored in patients with ACL rupture. Our hypothesis was that LL-BFR training triggers augmented gains in knee muscle strength and size, which are paralleled with transcriptional responses of hypoxia-regulated genes and myokines. Eighteen volunteers (age 37.5±9years) planned for ACL reconstruction, participated in the study. Twelve were divided between BFR group, performing 9 sessions of LL-BFR exercise, and SHAM-BFR group performing equal training with sham vascular occlusion. Six subjects served as a control for muscle biopsy analysis. Cross-sectional area (CSA) and isokinetic strength of knee muscles were assessed before and after the training. Change in CSAquad was significantly (p<0.01) larger in BFR (4.9%) compared with SHAM-BFR (1.3%). Similarly, change in peak torque of knee extensors was significantly (p<0.05) larger in BFR (14%) compared with SHAM-BFR (-1%). The decrease in fatigue index of knee extensors (6%) was larger (p<0.01) in BFR than in SHAM-BFR (2%). mRNA expression of HIF-1α in the vastus lateralis was reduced (p<0.05) in SHAM-BFR, while VEGF-A mRNA tended to be higher in BFR. The mRNA expression of myostatin and its receptor were reduced (p<0.05) in the semitendinosus after both types of training. Expression of IL-6, its receptors IL-6Rα and gp130, as well as musclin were similar in control and training groups. In conclusion, our results show augmented strength and endurance of knee extensors but less of the flexors. LL-BFR training is especially effective for conditioning of knee extensors in this population.

Optimizing amino acid balance in fish meal‐free diets for GIFT strain of Nile tilapia ( Oreochromis niloticus ) by deletion method

An indoor feeding trial was conducted to optimize the amino acid (AA) profile of the genetically improved farmed tilapia (GIFT) diet using the AA deletion method. Six corn–soy-based isonitrogenous and isoenergetic fishmeal-free diets with different AA profiles were formulated to evaluate the effects of crystalline AA supplementation on the growth performance, whole-body composition, muscle growth-related gene expression and haemato-biochemical responses of juvenile GIFT tilapia. Each diet was randomly assigned to triplicate groups of 30 fish (5.5 ± 0.3 g) per experimental unit, which were fed three times a day (09:00, 13:00 and 17:00 h) for a period of 60 days. Maximum growth performances and feed utilization were observed in fish fed a balanced diet and a -Trp diet compared with the AA-unsupplemented diet, whereas no significant differences were observed among fish fed –Met, –Lys and –Arg diets. Whole-body proximate composition and amino acid profile of GIFT tilapia were not significantly affected by diets with different amino acid profiles. Similarly, no significant differences were observed in blood biochemical responses, except glucose. However, significant (p < .05) differences were observed in haematological responses and mRNA expression of MyoD,myogenin and myostatin. Based on the growth performance and feed efficiency, the EAA pattern associated with –Trp diet was considered to be the optimum EAA ratio for maximum growth and feed utilization of juvenile GIFT tilapia.

Effect of Periodized Resistance Training on Skeletal Muscle During Androgen Deprivation Therapy for Prostate Cancer: A Pilot Randomized Trial.

Purpose:Prostate cancer survivors (PCS) receive androgen deprivation therapy (ADT) as treatment for recurrent cancer, yet ADT is associated with loss of skeletal muscle and physical function. Resistance training can counter both muscle and physical function loss; however, an understanding of the molecular responses of skeletal muscle to resistance training during ADT is still undefined. This sub-analysis of the original randomized, controlled pilot trial investigated effects of 12 weeks of periodized resistance training on mRNA expression of the anabolic genes IGF-1, myogenin, PGC-1α4 and the catabolic genes myostatin and MuRF-1 in skeletal muscle of PCS on ADT. Secondary aims investigated if changes in lean mass and physical function correlated with changes in mRNA expression.Methods:PCS on ADT (n = 17) were randomized to 12 weeks of supervised resistance training (EXE, n = 9) or home-based stretching (STRETCH, n = 8) 3 days per week. Outcomes were assessed at baseline and post-intervention. Muscle biopsies were analyzed by RT-PCR for mRNA expression. Body composition was assessed through dual-energy X-ray absorptiometry, and physical function through muscular strength, timed up and go, stair climb, and 400 m walk.Results:MuRF-1 mRNA expression was significantly greater in EXE compared to STRETCH post-intervention (P = .005). Change in MuRF-1 mRNA expression significantly correlated with improvements in strength and physical function (P < .05), while change in IGF-1 expression correlated with change in lean mass (P = .015).Conclusion:Twelve weeks of resistance training increased mRNA expression of MuRF-1 in skeletal muscle of PCS on ADT. Elevations in resting mRNA expression of IGF-1, myogenin and PGC-1α4, and reduction in mRNA expression of myostatin that are typically expected following resistance training were not observed.

Berberine Down-Regulated Myostatin Expression and Facilitated Metabolism via Smad Pathway in Insulin Resistant Mice.

ObjectiveTo explore the effect of berberine (BBR) on skeletal muscle mass and metabolism and the possible mechanism.MethodsEight-week-old male C57BL/6 mice were fed with a high-fat diet (HFD) for 8 weeks to establish the insulin resistance obesity model. Then, mice were randomly divided into two groups (normal chow diet (NCD) and HFD), while NCD and HFD were further classified into two groups respectively, which were NCD+CS (Carmellose Sodium), NCD+BBR, HFD+CS and HFD+BBR. After the BBR intervention, insulin tolerance test (ITT) and glucose tolerance test (GTT) were carried out. Metabolic parameters and inflammatory biomarkers were detected. Various parts of adipose tissue and gastrocnemius were separated and measured. The gastrocnemius muscle was selected for tissue staining. The mRNA expression of myostatin (Mstn) was tested by quantitative real-time PCR (RT-PCR). Western blotting was performed to detect the expression of Mstn, phosphatidylinositol 3-kinase (PI3K), protein kinase B (Akt), small ribonucleoprotein particle protein 2 (Smd2), small ribonucleoprotein particle protein 3 (Smd3), and small ribonucleoprotein particle protein 4 (Smd4).ResultsBoth body weights (P<0.01) and various parts of fat mass (P<0.001) were decreased significantly, while muscle mass was increased in the HFD group after being treated with BBR. Meanwhile, the glucose and lipid metabolic disorders as well as inflammation status were improved. RT-PCR and Western blotting analysis showed that, after being fed with HFD the expression of Mstn mRNA and Mstn were significantly increased, and decreased after being treated with BBR. Western blotting analysis also showed that, compared with the NCD group, the expressions of Smad2, Smad3, and Smad4 were all increased in the HFD group, but after being treated with BBR, the expressions of Smad3 and Smad4 were decreased.ConclusionOur study revealed that BBR could improve metabolic disorders and inflammation status, decrease Mstn expression, and increase skeletal muscle mass, which was associated with the Smad pathway.

The Effects of Cold Water Immersion and Active Recovery on Molecular Factors That Regulate Growth and Remodeling of Skeletal Muscle After Resistance Exercise.

Regular postexercise cooling attenuates muscle hypertrophy, yet its effects on the key molecular factors that regulate muscle growth and remodeling are not well characterized. In the present study, nine men completed two sessions of single-leg resistance exercise on separate days. On 1 day, they sat in cold water (10°C) up to their waist for 10 min after exercise. On the other day, they exercised at a low intensity for 10 min after exercise. Muscle biopsies were collected from the exercised leg before, 2, 24, and 48 h after exercise in both trials. These muscle samples were analyzed to evaluate changes in genes and proteins involved in muscle growth and remodeling. Muscle-specific RING finger 1 mRNA increased at 2 h after both trials (P < 0.05), while insulin-like growth factor (IGF)-1 Ec, IGF-1 receptor, growth arrest and DNA damage-inducible protein 45, collagen type I alpha chain A, collagen type III alpha chain 1, laminin and tissue inhibitor of metallopeptidase 1 mRNA increased 24−48 h after both trials (P < 0.05). By contrast, atrogin-1 mRNA decreased at all time points after both trials (P < 0.05). Protein expression of tenascin C increased 2 h after the active recovery trial (P < 0.05), whereas FoxO3a protein expression decreased after both trials (P < 0.05). Myostatin mRNA and ubiquitin protein expression did not change after either trial. These responses were not significantly different between the trials. The present findings suggest that regular cold water immersion attenuates muscle hypertrophy independently of changes in factors that regulate myogenesis, proteolysis and extracellular matrix remodeling in muscle after exercise.

MOTS‐c inhibits high‐fat diet‐induced muscle wasting by suppressing myostatin expression via the PTEN/AKT/FOXO1 signaling pathway

Insulin resistance is thought to contribute to the development of muscle wasting. MOTS‐c, a novel mitochondrial‐derived peptide, improves insulin resistance in skeletal muscle, but its effects on muscle wasting have yet to be explored. Here, we used a diet‐induced obese mouse model to examine the effect of MOTS‐c administration on high fat diet‐induced muscle wasting. Three weeks of MOTS‐c administration by intraperitoneal (IP) injection in high‐fat diet fed mice resulted in higher total skeletal muscle mass of soleus, gastrocnemius, and plantaris compared to its high‐fat diet fed control group. Myostatin mRNA expression levels were significantly decreased in the MOTS‐c treated group compared to the high‐fat diet fed controls in the gastrocnemius muscle. Furthermore, myostatin mRNA expression negatively correlated with the total skeletal muscle mass of soleus, gastrocnemius, and plantaris. To examine the detailed mechanism of MOTS‐c action, we injected high‐fat diet fed mice with MOTS‐c for eight weeks and detected significantly lower plasma myostatin levels than high‐fat diet fed controls, as well as mRNA expression of myostatin and atrogin‐1 in the skeletal muscle. We further examined the upstream signaling pathways of myostatin regulation in the skeletal muscle and showed that MOTS‐c treatment inhibited PTEN activity, leading to elevated AKT phosphorylation and inhibition of FOXO1 transcription activity, resulting in myostatin and atrogin‐1 suppression. These results suggest that potent MOTS‐c analogues could potentially treat conditions such as high‐fat diet‐induced skeletal muscle wasting, as well as other muscle wasting phenotypes including sarcopenia, and that circulating levels of myostatin may serve as a pharmacodynamic biomarker of MOTS‐c activity.

Ammonia Induces a Myostatin-Mediated Atrophy in Mammalian Myotubes, but Induces Hypertrophy in Avian Myotubes

Ammonia, a byproduct of protein catabolism that is generally regarded as toxic, is processed by the liver for excretion. In diseases resulting in hepatic insufficiency, circulating ammonia levels increase dramatically, ensuing secondary disorders. Sarcopenia, or loss of muscle mass, is commonly associated with hyperammonemia. In mammalian models of cirrhosis, increased myostatin is consistent, contributes to muscle autophagy, and reduces satellite cell activation and differentiation, whereas, avian species show a positive myogenic response to ammonia. The objective of the study was to elucidate the effect of ammonia in chicken, mouse, and rat derived myotubes. Primary myoblasts were isolated from the pectoralis major (breast) and biceps femoris (thigh) of embryonic day 17 chicken embryos, and from the hindlimbs of 3-day-old rat pups. C2C12 cells were used for mouse myoblasts. Myotubes were exposed to 10mM ammonium acetate (AA) or 10mM sodium acetate (SA) for 24 hours to determine myogenic response to ammonia. Relative expression of myostatin mRNA, determined by quantitative real-time PCR, was significantly higher in mammalian myotubes compared to chicken myotubes (P < 0.001). Western blot analysis of myostatin protein confirmed a significant increase in ammonia treated rat myotubes, while chicken breast myotubes showed a significant decrease in myostatin (P < 0.05). Myotube diameter significantly increased in chicken breast and thigh cultures treated with ammonia, while diameter was significantly reduced in mouse and rat myotubes (P < 0.05). Intracellular glutamine is significantly higher in chicken thigh, but not breast, myotubes treated with AA compared to SA treated myotubes (P < 0.05). To investigate fiber type differences in ammonia metabolism, Western blot analysis of protein from AA and SA treated myotubes was examined for fast and slow myosin heavy chain isoforms. AA treatment resulted in a higher ratio of fast to slow isoforms of myosin heavy chain in both types of chicken myotubes, while fast isoforms were decreased in AA treated mouse and rat myotubes. These data demonstrate that chicken myotubes respond positively to ammonia while rodent myotubes respond negatively. Further, there is evidence that ammonia induces a fast fiber type shift in avian muscle, but a slow phenotype shift in mammalian muscle.

Effects of equine myostatin (MSTN) genotype variation on transcriptional responses in Thoroughbred skeletal muscle

Myostatin gene (MSTN) variation influences distance aptitude in Thoroughbreds as a consequence of functional physiological effects including skeletal muscle fibre type and muscle hypertrophy variation. A promotor region short interspersed nuclear element (SINE) insertion, tagged by SNP g.66493737-C, alters MSTN mRNA expression. We tested the hypothesis that skeletal muscle gene expression varies among MSTN genotypes due to differential up- or down-stream gene signalling pathways that may be influenced by exercise and training and consequently contribute to variation in exercise phenotypes. Skeletal muscle biopsies were collected from Thoroughbreds previously genotyped for MSTN (n=35 CC, n=50 CT, n=9 TT) at three different time-points: untrained at rest (UR), untrained after exercise (UE) and trained at rest (TR). Gene differential expression (DE) was determined from RNAseq data using DESeq2 (Benjamini-Hochberg P-value &lt;0.05). Functional over-representation analysis was performed in DAVID. In UR samples, one, nine and 47 genes were DE between CC vs CT, CT vs TT and C:C vs TT, respectively. The OSGEPL1 gene, located &lt;250 Kb proximal to MSTN, was DE among all cohorts. Six genes were DE in UE between CC vs TT including OSGEPL1, FGF10 and COQ8A. There was significant enrichment for GO categories related to mitochondria in TR. Comparison of the exercise response (UR vs UE) revealed patterns of expression that were opposing; i.e. CHRNG was 0.857 log2FC in the TT cohort but 2.055 log2FC in the CC cohort. Genes located in proximity to MSTN and involved in mitochondrial function were most significantly different among genotype cohorts. Patterns of DE among genotypes suggests gene-regulated influence on the phenotype. Understanding these patterns may assist genotype-guided training strategies.

Expression of MSTN gene and its correlation with pectoralis muscle fiber traits in the domestic pigeons (Columba livia)

Myostatin (MSTN) is a negative regulator of skeletal muscle growth and plays an important role in muscle development. In this research, we constructed a tissue expression profile of the pigeon MSTN gene in eight tissues and a spatio-temporal expression profile in the pectoral muscle using qRT-PCR method. And the pectoralis muscle fiber traits during pigeon post-hatching stages at 1, 7, 14, 21, and 28 D were analyzed through the paraffin sections. Then the correlations between the muscle fiber diameter, cross-sectional area, density, and the expression of MSTN in the pectoral muscle were analyzed. Results showed that MSTN mRNA was mainly expressed in breast muscle, heart, spleen, and kidney and it was almost unexpressed in the liver and lungs. Moreover, the MSTN mRNA expression level in breast muscle was significantly higher than that in other tissues (P < 0.05), and showed an interesting trend that it decreased in the first week and then increased with age. Meanwhile, decrease of myostatin transcripts was accompanied by the down-regulation of Myf5 and the up-regulation of MyoG during the first week post-hatching. In addition, the paraffin sections analysis results revealed that the diameter and cross-sectional area of pectoralis muscle fiber significantly increased with age (P < 0.05), and a significant positive correlation was shown between the MSTN gene expression level and muscle fiber diameter (P < 0.05). These fundamental researches might contribute to further understanding of the roles MSTN played in the post-hatching muscle fiber development in pigeon.

Replacement of fish meal with soy protein concentrate in diet of juvenile rice field eel Monopterus albus

Among plant protein sources, soy protein concentrate (SPC) has lower anti-nutritional factors and higher protein content. The aim of this study was to evaluate the effect of replacing fish meal in diet of rice field eel Monopterus albus with soy protein concentrate on growth performance, serum biochemical indices, intestinal digestive enzymes and growth-related genes expression in skeletal muscle. Six isonitrogen (45% crude protein) and isolipidic (5.5% crude lipid) diets were formulated with 0 g/kg, 8.5 g/kg, 17 g/kg, 25.5 g/kg, 34 g/kg and 42.5 g/kg SPC inclusion to replace 0%, 15%, 30%, 45%, 60% and 75% of fish meal (S0 (control), S8.5, S17, S25.5, S34, S42.5, respectively). Each diet was randomly assigned to triplicate groups of 100 fish per net cage (mean initial weight 25.56 ± 0.12 g). The fish were fed once at 18:00 per day for 56 days. Results showed that weight gain and feed intake significantly decreased in fish fed S42.5 (P < 0.05). Feed conversion rate was significantly higher in S34 and S42.5 groups compared to the other treatments (P < 0.05). No significant effects were found on hepatosomatic index and body composition among treatments. Viscerosomatic index significantly decreased with the increasing levels of SPC inclusion. Amylase and lipase activities in intestine peaked at S17 group. Dietary SPC supplementation significantly reduced the activities of intestine trypsin and serum glutamic oxalacetic transaminase and glutamate pyruvate transaminase as well as the content of serum triglyceride, total cholesterol, low density lipoprotein cholesterol and malondialdehyde, but significantly elevated the activities of catalase and total antioxidant capacity (P < 0.05). The superoxide dismutase activity had a rising trend compared to the control. High supplementation levels of dietary SPC down-regulated myogenic determination factor and myogenin mRNA expression, but up-regulated myostatin mRNA expression. These results suggested that fish meal could be partially replaced by SPC in diet of M. albus and the optimal supplementation level of SPC was 26% by using broken-line model curve. Replacing fish meal with dietary SPC has benefit in enhancing serum antioxidant capacity, improving serum lipid profile and modulating growth-related genes expression pattern in skeletal muscle of M. albus.

Differentiation of Bioengineered Skeletal Muscle within a 3D Printed Perfusion Bioreactor Reduces Atrophic and Inflammatory Gene Expression.

Bioengineered skeletal muscle tissues benefit from dynamic culture environments which facilitate the appropriate provision of nutrients and removal of cellular waste products. Biologically compatible perfusion systems hold the potential to enhance the physiological biomimicry of in vitro tissues via dynamic culture, in addition to providing technological advances in analytical testing and live cellular imaging for analysis of cellular development. To meet such diverse requirements, perfusion systems require the capacity and adaptability to incorporate multiple cell laden constructs of both monolayer and bioengineered tissues. This work reports perfusion systems produced using additive manufacturing technology for the in situ phenotypic development of myogenic precursor cells in monolayer and bioengineered tissue. Biocompatibility of systems 3D printed using stereolithography (SL), laser sintering (LS), and PolyJet outlined preferential morphological development within both SL and LS devices. When exposed to intermittent perfusion in the monolayer, delayed yet physiologically representative cellular proliferation, MyoD and myogenin transcription of C2C12 cells was evident. Long-term (8 days) intermittent perfusion of monolayer cultures outlined viable morphological and genetic in situ differentiation for the live cellular imaging of myogenic development. Continuous perfusion cultures (13 days) of bioengineered skeletal muscle tissues outlined in situ myogenic differentiation, forming mature multinucleated myotubes. Here, reductions in IL-1β and TNF-α inflammatory cytokines, myostatin, and MuRF-1 atrophic mRNA expression were observed. Comparable myosin heavy chain (MyHC) isoform transcription profiles were evident between conditions; however, total mRNA expression was reduced in perfusion conditions. Decreased transcription of MuRF1 and subsequent reduced ubiquitination of the MyHC protein allude to a decreased requirement for transcription of MyHC isoform transcripts. Together, these data appear to indicate that 3D printed perfusion systems elicit enhanced stability of the culture environment, resulting in a reduced basal requirement for MyHC gene expression within bioengineered skeletal muscle tissue.

Effects of dietary supplementation with betaine on muscle growth, muscle amino acid contents and meat quality in Cherry Valley ducks.

The effects of dietary betaine supplementationon growth performance, carcass characteristics, muscle amino acid contents, meat quality, antioxidant capacity, myogenic gene expression and mechanistic target of rapamycin (mTOR) signalling pathway in Cherry Valley ducks were evaluated. A total of 720 1-day-old Cherry Valley ducks were randomly distributed into four groups with six replicates of 30 birds for a 42-day feeding trial. Ducks were fed a basal diet supplemented with 0 (control), 250, 500 or 1,000mg/kg betaine, respectively. Growth performance was not affected by betaine. Incremental levels of betaine linearly (p<0.05) increased the breast muscle yield and linearly (p<0.05) decreased the subcutaneous fat thickness and the abdominal fat yield. The contents of methionine, serine, glycine, glutamate and total non-essential amino acid in breast muscle were linearly (p<0.05) increased by betaine supplementation. With increasing betaine levels, the drip loss and the content of malondialdehyde (MDA) were linearly (p<0.05) decreased, and the redness of meat (linear p<0.05), the activities of catalase (CAT) (linear p<0.05) and total superoxide dismutase (T-SOD) (linear p<0.05, quadratic p<0.05) were increased. Moreover, the myogenic differentiation factor 1 (MyoD1) mRNA expression and the mTOR mRNA expression and protein phosporylation were linearly (p<0.05) up-regulated, and the myostatin (MSTN) mRNA expression was linearly (p<0.05) down-regulatedby betaine supplementation. Overall, this study indicated that betaine supplementation did not affect the growth performance of Cherry Valley ducks, but could linearly increase some amino acid contents in breast muscle, especially glycine, and increase muscle antioxidant activity to improve meat quality. Moreover, betaine supplementation could improve the breast muscle yield by increasing MyoD1 mRNA expression, decreasing MSTN mRNA expression and regulating mTOR signalling pathway.

One Week of Step Reduction Lowers Myofibrillar Protein Synthesis Rates in Young Men.

Across the lifespan, physical activity levels decrease and time spent sedentary typically increases. However, little is known about the impact that these behavioral changes have on skeletal muscle mass regulation. The primary aim of this study was to use a step reduction model to determine the impact of reduced physical activity and increased sedentary time on daily myofibrillar protein synthesis rates in healthy young men. Eleven men (22 ± 2 yr) completed 7 d of habitual physical activity (HPA) followed by 7 d of step reduction (SR). Myofibrillar protein synthesis rates were determined during HPA and SR using the deuterated water (H2O) method combined with the collection of skeletal muscle biopsies and daily saliva samples. Gene expression of selected proteins related to muscle mass regulation and oxidative metabolism were determined via real time reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Daily step count was reduced by approximately 91% during SR (from 13,054 ± 2763 steps per day to 1192 ± 330 steps per day; P < 0.001) and this led to an increased contribution of sedentary time to daily activity (73% ± 6% to 90% ± 3%; P < 0.001). Daily myofibrillar protein synthesis decreased by approximately 27% from 1.39 ± 0.32%·d during HPA to 1.01 ± 0.38%·d during SR (P < 0.05). Muscle atrophy F-box and myostatin mRNA expression were upregulated, whereas mechanistic target of rapamycin, p53, and PDK4 mRNA expression were downregulated after SR (P < 0.05). One week of reduced physical activity and increased sedentary time substantially lowers daily myofibrillar protein synthesis rates in healthy young men.

Myostatin alters with exercise training in diabetic rats; possible interaction with glycosylated hemoglobin and inflammatory cytokines

The role of myostatin (MSTN) in the regulation of energy homeostasis has been known and that MSTN inhibition can attenuate the development of diabetes. However, the response of MSTN to exercise in type 1 diabetes (T1DM) is unknown. This study aimed to investigate the alteration of MSTN following aerobic exercise training in diabetic rats and its possible interaction with glycosylated hemoglobin (HbA1c) and inflammatory cytokines. Forty-eight male Wistar rats were divided into non-diabetic untrained, non-diabetic trained, diabetic untrained and diabetic trained groups. To induce T1DM, rats received an intraperitoneal injection of STZ (60 mg·kg−1). Treadmill exercise was performed for six weeks, five days/week. HbA1c was estimated, MSTN mRNA expression in skeletal muscle was measured, and plasma MSTN and inflammatory cytokines including interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1β) were determined. Results revealed a significant decrease of HbA1c and plasma inflammatory cytokines (IL-6, TNF-α and IL-1β) followed by a significant decrease of plasma and skeletal muscle MSTN in diabetic trained rats versus non-diabetic untrained and diabetic untrained rats after the experimental period. Moreover, in diabetic untrained and diabetic trained rats, a significantly positive correlation (change versus change) of plasma MSTN with HbA1c and plasma IL-6, TNF-α and IL-1β was found. In conclusion, this study indicated that aerobic exercise training by a decrease of HbA1c and plasma IL-6, TNF-α and IL-1β could decrease MSTN levels in plasma and skeletal muscle in T1DM. Furthermore, the effective influence of exercise may be reflected by changes of MSTN in diabetic rats.

Expression of Myostatin (Mstn) and Myogenin (Myog) Genes in Zi And Rhine Goose and Their Correlation with Carcass Traits

The aim of this study was to investigate the effects of Myostatin (MSTN) and MyoGenin (MyoG) on goose skeletal muscle growth. In this study, MSTN and MyoG gene expression in breast and leg muscle of Zi and Rhine goose were detected by Real-time Polymerase Chain Reaction (PCR), and the correlations between genes expression levels and carcass traits were investigated. The results showed that the breast muscle weight and breast muscle percentage of Rhine goose were significantly higher than Zi goose (p<0.01). MSTN mRNA and MyoG mRNA expression in breast muscle of Zi goose were significantly higher than that of Rhine goose and the level of MSTN in leg muscle of Rhine was significantly higher than that of Zi goose (p<0.01). There was a significant difference between MSTN mRNA expression in breast muscle and in leg muscle of Zi goose (p<0.01). MSTN mRNA expression in leg muscle was significantly higher than that of breast muscle of Rhine goose (p<0.05). There was a significant difference between MyoG mRNA expression in breast muscle and in leg muscle of Zi goose and Rhine goose (p<0.01). There was a negative correlation between MSTN mRNA expression in breast muscle and body weight, breast muscle weight and breast muscle percentage.

GH replacement titrated to serum IGF-1 does not reduce concentrations of myostatin in blood or skeletal muscle

ObjectiveTraditional weight-based regimens of GH replacement are more effective at reversing the loss of skeletal muscle in GH-deficient adults than currently recommended regimens, where the dose of GH is increased to restore serum concentrations of IGF-1. While weight-based regimens increase concentrations of IGF-1 and decrease concentrations of myostatin, it is not known whether the reduced effectiveness of individually titrated GH regimens is due to ongoing hypersecretion of myostatin. Consequently, the aims of this study were to determine whether concentrations of myostatin in blood and skeletal muscle are increased in GH-deficient adults, and whether these concentrations are decreased by GH replacement regimens titrated to restore serum IGF-1. DesignTwenty-six GH deficient adults (18 men and 8 women) were treated with individualised regimens of recombinant human GH aiming to achieve serum concentrations of IGF-1 within one standard deviation of the age- and gender-adjusted mean. Plasma concentrations of myostatin were measured at baseline and after 6 months of treatment were compared to fifteen healthy controls (9 men and 6 women). Skeletal muscle biopsies were performed in 19 of these GH-deficient adults (15 men and 4 women) and 10 of the healthy controls (6 men and 4 women). Expression of IGF-1 and myostatin mRNA was determined by qPCR. ResultsConcentrations of IGF-1 in serum and mRNA in skeletal muscle were reduced, and concentrations of myostatin in plasma and mRNA in skeletal muscle were increased in GH-deficient adults at baseline (P < .05 versus healthy controls). Despite restoring concentrations of IGF-1, GH replacement did not reduce concentrations of myostatin in either blood or skeletal muscle. Concentrations of IGF-1 and myostatin in both blood and skeletal muscle were positively correlated in GH-deficient adults at baseline (P < .05), but not in GH-replete adults. ConclusionsConcentrations of myostatin in blood and skeletal muscle are increased in GH-deficient adults. Despite normalising concentrations of IGF-1, individualised regimens of GH replacement do not reduce concentrations of myostatin in blood or skeletal muscle. Ongoing hypersecretion of myostatin may explain why individually titrated GH replacement regimens are less effective than higher weight-based regimens in increasing skeletal muscle mass.

PO-306 The effect of four weeks hypoxic resistance training on myostatin and follistatin expression in skeletal muscle of rats

Objective Loss of skeletal muscle weight is a common phenomenon in hypoxic environment. It has been recognized that resistance training can reduce hypoxia-induced skeletal muscle atrophy, but its molecular mechanism is still unclear. Myostatin is a major factor that inhibits muscle growth and differentiation, and Follistatin can inhibit Myostatin. Therefore, this study is to clarify the effect of 4-week hypoxic resistance exercise on Myostatin and Follistatin gene expression in skeletal muscle of rats.&#x0D; Methods Twenty four 8-week-old male SD rats were randomly divided into normoxic control group (group C: 6 rats), normoxic exercise group (group R: 6 rats), hypoxic control group (group H: 6 rats) and hypoxic exercise group (group HR: 6 rats). Rats in each hypoxic group were fed in a hypoxic chamber (atmospheric hypoxia) with oxygen concentration of 12.7% (simulated 4000m altitude). Rats in each exercise group were trained according to the rat's resistance training program developed in our laboratory. After all the intervention, DEXA was used to analyze the body composition. The soleus, extensor digitorum longus and biceps brachii muscles of rats were taken and the wet weight of individual muscles was measured. The data were processed by SPSS17.0 statistical software. The expression level of skeletal muscle mRNA was expressed as "median (25-75%)" and the data of body composition and muscle wet weight were expressed as"mean±standard deviation". The differences between the groups were evaluated using a one-way analysis of variance (ANOVA) test. The significance level for the study was less than 0.05.&#x0D; Results Body composition analysis after 4 weeks of hypoxic intervention showed that the body weight of rats in group H decreased significantly (p=0.012), and the muscle mass decreased more significantly (p&lt;0.001). But resistance exercises obviously reduced the muscle atrophy (p&lt;0.01) caused by hypoxia. After analyzing the changes of the wet weight of individual muscles, it was found that the wet weight of biceps brachii in HR group was significantly higher than that in H group (p=0.048). After 4 weeks of hypoxic intervention and hypoxic resistance exercise, the expression of Myostatin mRNA in individual muscles of each group changed differently. The expression of Myostatin mRNA in soleus muscle of H group was significantly higher than that of C group (371.2%) after 4 weeks of hypoxia intervention. Myostatin mRNA expression in soleus and biceps brachii of HR group was significantly lower than that of H group (591.1% and 478.4% respectively). However, there was no significant difference in the expression level of Myostatin mRNA in the extensor digitorum longus between each group (p=0.259). The change of Follistatin mRNA expression in different groups also showed a different trend. The expression of Follistatin mRNA in soleus muscle and biceps brachii muscle was significantly different among groups (p=0.003, p=0.004, respectively). However, there was no significant difference in the expression level of Follistatin mRNA in the extensor digitorum longus between each group (p=0.734). Myostatin mRNA/Follistatin mRNA ratio (M/F) showed a more significant difference. The M/F ratio of soleus muscle in group H was significantly lower than that in group C (p&lt;0.001), but the M/F ratio in group HR was significantly higher than that in group H (p&lt;0.001). The M/F ratio of biceps brachii in group H was significantly lower than that in group C (p&lt;0.001), but the M/F ratio in group HR showed a higher trend than that in group H (p=0.051).&#x0D; Conclusions Hypoxic exposure results in an increase in Myostatin mRNA expression in skeletal muscle, but hypoxic resistance exercise reduces such an increase. On the contrary, the level of Follistatin mRNA expression in skeletal muscle decreased after hypoxic exposure, and hypoxic resistance exercise could slow down the decline. As a result, rat resistance exercise significantly slowed down hypoxia-induced muscle atrophy. In conclusion, the mutual restriction between Myostatin and Follistatin is one of the main links of resistance exercise to reduce hypoxia-induced skeletal muscle atrophy. However, the process of resistance training to reduce the hypoxia-induced skeletal muscle atrophy is very complex. There are many molecular signaling pathways involved, which need further study.

Myostatin is expressed in bovine ovarian follicles and modulates granulosal and thecal steroidogenesis

Myostatin plays a negative role in skeletal muscle growth regulation but its potential role in the ovary has received little attention. Here, we first examined relative expression of myostatin (MSTN), myostatin receptors (ACVR1B, ACVR2B and TGFBR1) and binding protein, follistatin (FST), in granulosa (GC) and theca (TC) cells of developing bovine follicles. Secondly, using primary GC and TC cultures, we investigated whether myostatin affects steroidogenesis and cell number. Thirdly, effects of gonadotropins and other intrafollicular factors on MSTN expression in GC and TC were examined. MSTN, ACVR1B, TGFBR1, ACVR2B and FST mRNA was detected in both GC and TC at all follicle stages. Immunohistochemistry confirmed follicular expression of myostatin protein. Interestingly, MSTN mRNA expression was lowest in GC of large oestrogen-active follicles whilst GC FST expression was maximal at this stage. In GC, myostatin increased basal CYP19A1 expression and oestradiol secretion whilst decreasing basal and FSH-induced HSD3B1 expression and progesterone secretion and increasing cell number. Myostatin also reduced IGF-induced progesterone secretion. FSH and dihydrotestosterone had no effect on granulosal MSTN expression whilst insulin-like growth factor and tumour necrosis factor-alpha suppressed MSTN level. In TC, myostatin suppressed basal and LH-stimulated androgen secretion in a follistatin-reversible manner and increased cell number, without affecting progesterone secretion. LH reduced thecal MSTN expression whilst BMP6 had no effect. Collectively, results indicate that, in addition to being potentially responsive to muscle-derived myostatin from the circulation, myostatin may have an intraovarian autocrine/paracrine role to modulate thecal and granulosal steroidogenesis and cell proliferation/survival.

Regulation of myostatin expression is associated with growth and muscle development in commercial broiler and DMC muscle

Myostatin is a negative regulator of skeletal muscle growth. Muscle tissue is the largest tissue in the body and influences body growth. Commercial Avian broiler chickens are selected for high growth rate and muscularity. Daweishan mini chickens are a slow growing small-sized chicken breed. We investigated the relations between muscle (breast and leg) myostatin mRNA expression and body and muscle growth. Twenty chickens per breed were slaughtered at 0, 30, 60, 90, 120, and 150 days of age. Body and muscle weights were higher at all times in Avian chickens. Breast muscle myostatin expression was higher in Avian chickens than in Daweishan mini chickens at day 30. Myostatin expression peaked at day 60 in Daweishan mini chickens and expression remained higher in breast muscle. Daweishan mini chickens myostatin expression correlated positively with carcass weight, breast and leg muscle weight from day 0 to 60, and correlated negatively with body weight from day 90 to 150, while myostatin expression in Avian chickens was negatively correlated with carcass and muscle weight from day 90 to 150. The results suggest that myostatin expression is related to regulation of body growth and muscle development, with two different regulatory mechanisms that switch between days 30 and 60.