Decrease In Myostatin Research Articles

Synergistic Effects of Korean Mistletoe and Apple Peel Extracts on Muscle Strength and Endurance.

Muscular strength and endurance are vital for physical fitness. While mistletoe extract has shown efficacy in significantly increasing muscle strength and endurance, its accessibility is limited. This study explores combining mistletoe and apple peel extracts as an effective muscle health supplement. Analyses of histology, RNA, and protein in the combined extract-treated mouse group demonstrated significant enhancements in muscle strength and endurance, evidenced by larger muscle fibers, improved mitochondrial function, and a higher ratio of type I and IIa muscle fibers. Combining half doses of each extract resulted in greater improvements than using each extract separately, indicating a synergistic effect. Pathway analysis suggests that the observed synergy arises from complementary mechanisms, with a mistletoe extract-induced decrease in myostatin (MSTN) and an apple peel extract-induced increase in IGF1, leading to a sharp rise in AKT, S6K, and MuRF1, which promote myogenesis, along with a significant increase in PGC-1α, TFAM, and MEF2C, which are critical for mitochondrial biogenesis. This research provides practical insights into developing cost-effective, natural supplements to enhance muscle performance and endurance, with potential applications in athletic performance, improving muscle growth and endurance in children, and addressing age-related muscle decline.

The Effect of Selected Aquatic Training on Serum Levels of Insulin-like Growth Factor-1 and Mmyostatin in Middle-aged Male Swimmers

Background and Objectives Sarcopenia is one of the important and prevalent disorders that occurs with age and is associated with a significant reduction in muscle strength and volume. The purpose of this study was to investigate the effect of selected aquatic training on serum levels of insulin-like growth factor-1 and myostatin in middle-aged male swimmers. Subjects and Methods Twenty-two men meeting the inclusion criteria were recruited and randomly assigned to either the experimental group (n = 11) or the control group (n = 11). The training program followed a progressive overload structure, employing three sessions per week with escalating difficulty and intensity. This design aligns with the principle of overload, which posits that gradually increasing training demands leads to adaptation and improvement. Plasma levels of IGF-1 and myostatin were measured (before and 48 hours after the protocol). The data were analyzed using the statistical test of covariance (ANCOVA) at a significance level of P<0.05. Results The intragroup evaluation of the data showed that there is a significant difference between the pre-test and post-test scores of the experimental group in IGF-1 and myostatin variables (P<0.05). The results of ANCOVA indicated that the selected aquatic training led to a significant increase in plasma levels of IGF-1 (P<0.05) and a significant decrease in myostatin (P<0.05) in the experimental group compared to the control group. Conclusion According to the results of this research, eight weeks of selected aquatic training changed the resting levels of factors related to muscular atrophy in middle-aged male swimmers. For this reason, this type of exercise can be effective in muscle rehabilitation and improving the physical fitness of these people. However, further investigations seem necessary.

Levels of Myostatin, Adiponectin and Lipid Profile in Hyperlipidemia Patients

Background: Excess fat is one of the biggest risk factors for the development of heart disease and one of the top five leading causes of death. The researchers expect from their study that deaths due to cardiovascular diseases will increase from (17.3) million cases in 2017 to (23.6) million deaths by 2030.
 Aim: Determination of the concentration of lipid profile variables (TC, TG, HDL-C, LDL-C, VLDL-C). Estimating the concentration of some hormones such as myostatin and adiponectin in the serum of study samples in males and females with hyperlipidemia at different ages.
 Materials and methods: The study included collecting (90) samples and dividing them into two groups (20-60).Blood samples were collected from the vein (10ml) using medical syringes, and the blood was placed in plastic tubes, where the samples were left for (15-20) minutes at a temperature of 37 °C in a water bath until the blood coagulated, and then the samples were separated in a centrifuge.
 Results: the results showed a significant increase in each of TC, TG, LDL and VLDL, and a significant decrease in Myostatin and HDL, while the results showed no significant difference in Adiponectin. In females compared to healthy subjects the results showed a significant increase in TC, TG, LDL, and VLDL, and the results showed a significant decrease in HDL, while the results showed that there was no significant difference in both Adiponectin and Myostatin.
 Conclusions: We conclude from our current study that hyperlipidemia is associated with an imbalance in the level of muscular lipid movements and is therefore considered a risk factor for the occurrence of cardiovascular diseases and requires follow-up and a healthy diet with treatment.

New Strains of Akkermansia muciniphila and Faecalibacterium prausnitzii are Effective for Improving the Muscle Strength of Mice with Immobilization-Induced Muscular Atrophy.

Muscular atrophy is a muscle disease in which muscle mass and strength decrease due to aging, injury, metabolic disorders, or chronic conditions. Proteins in muscle tissue are degraded by the ubiquitin-proteasome pathway, and atrophy accelerates this pathway. Akkermansia muciniphila and Faecalibacterium prausnitzii strains are effective agents against metabolic and inflammatory diseases in next-generation probiotic research. In this study, we evaluated the efficacy of A. muciniphila strain EB-AMDK19 and F. prausnitzii strain EB-FPDK11 in a mouse model of muscular atrophy, since atrophy inhibits energy metabolism and immune activation. After oral administration of each strain for 4 weeks, the hind legs of the mice were fixed with a plaster cast to immobilize them for a week. As a result, the administration of EB-AMDK19 and EB-FPDK11 strains improved grip strength but did not increase muscle mass. At the molecular level, A. muciniphila and F. prausnitzii treatments decreased the expression levels of ubiquitin-proteasome genes, atrogin-1, MuRF, and cathepsin L. They increased the expression level of the mitochondrial biogenesis regulatory gene, PGC-1α. The effect of the strains was confirmed by a decrease in myostatin. Furthermore, A. muciniphila and F. prausnitzii modulated the immune function by enhancing ZO-1 and inhibiting IL-6. In particular, EB-AMDK19 promoted the expression of IL-10, an anti-inflammatory cytokine. These results suggest that A. muciniphila and F. prausnitzii may have beneficial effects on muscular atrophy, verified by newly isolated EB-AMDK19 and EB-FPDK11 as potential next-generation probiotics.

Combined training improves the diagnostic measures of sarcopenia and decreases the inflammation in HIV-infected individuals.

BackgroundHIV‐related sarcopenia is an emerging health issue that often remains undiagnosed and can lead to reduced quality of life, independence, and premature death if untreated. This study investigated the effects of a 6 month combined training (resistance plus aerobic exercise) (CT) intervention on diagnostic measures of sarcopenia, including grip strength, appendicular lean mass index (ALMI), and gait speed.MethodsForty participants were randomized into either a CT group (n = 20; age = 38.3 ± 4.9 years) or a control group (CON; n = 20; age = 37.9 ± 5.1 years). Participants in the CT group performed three supervised sessions per week for 6 months, consisting of weekly reverse linear periodized resistance training followed by 20 min aerobic training. Participants in the CON group were instructed to continue with their current lifestyle habits. Assessments were completed at baseline and after 6 months. Statistical analyses were performed using a two‐way analysis of covariance (ANCOVA) adjusted for sex and preintervention values. Primary outcomes included grip strength, ALMI, and gait speed. Secondary outcomes were changes in levels of pro‐inflammatory cytokines (IL‐6 and TNF‐α), IGF‐1, and myostatin. Associations were explored between changes in inflammatory markers (IL‐6 and TNF‐α), gait speed, and ALMI with grip strength.ResultsA significant increase in ALMI was found for CT compared with CON (0.29 ± 0.13 kg/m2 vs. −0.11 ± 0.14 kg/m2, respectively; P < 0.001). Significant improvements in grip strength (7.86 ± 8.50 kg for CT vs. −1.58 ± 2.47 kg for CON) and gait speed (0.16 ± 0.07 m/s2 for CT vs. −0.06 ± 0.52 m/s2 for CON; both P < 0.001) were also observed in CT compared with CON. Reduction in inflammatory biomarkers was found in CT compared with CON (IL‐6; TNF‐α, both P < 0.001). An increase in IGF‐1 (74.36 ± 56.64 pg/mm3 for CT vs. 7.19 ± 99 pg/mm3 for CON; P < 0.001) and a decrease in myostatin (−158.90 ± 62.03 pg/mm3 for CT vs. −43.33 ± 146.60 pg/mm3 for CON; P < 0.001) was found following CT compared with the CON group. Change in grip strength was correlated with changes in IL‐6 (r = −0.65, P < 0.001), TNF‐α (r = −0.63, P < 0.001), gait speed (r = 0.63, P < 0.001), and ALMI (r = 0.54, P = 0.001), but not IGF‐1 and myostatin. No adverse events were recorded, and compliance with the CT exercise sessions was high (>85%).ConclusionsCombined training appears to be an effective means to counteract sarcopenia and improve various inflammatory markers and growth hormones in people living with HIV.

Nordic Walking Rather Than High Intensity Interval Training Reduced Myostatin Concentration More Effectively in Elderly Subjects and the Range of This Drop Was Modified by Metabolites of Vitamin D.

The COVID-19 pandemic and subsequent self-isolation exacerbated the problem of insufficient amounts of physical activity and its consequences. At the same time, this revealed the advantage of vitamin D. Thus, there was a need to verify the effects of those forms of training that can be performed independently. In this study, we examined the effects of Nordic walking (NW) and high intensity interval training (HIIT) with regard to the impact of the metabolite vitamin D. We assigned 32 overweight adults (age = 61 ± 12 years) to one of two training groups: NW = 18 and HIIT = 14. Body composition assessment and blood sample collection were conducted before starting the training programs and a day after their completion. NW training induced a significant decrease in myostatin (p = 0.05) concentration; however, the range was dependent on the baseline concentrations of vitamin D metabolites. This drop was accompanied by a significant negative correlation with the decorin concentration. Unexpectedly, NW caused a decrement in both forms of osteocalcin: undercarboxylated (Glu-OC) and carboxylated-type (Gla-OC). The scope of Glu-OC changes was dependent on a baseline concentration of 25(OH)D2 (r = −0.60, p = 0.01). In contrast, the HIIT protocol did not induce any changes. Overall results revealed that NW diminished the myostatin concentration and that this effect is more pronounced among adults with a sufficient concentration of vitamin D metabolites.

(-)-Epicatechin-Enriched Extract from Camellia sinensis Improves Regulation of Muscle Mass and Function: Results from a Randomized Controlled Trial.

Loss of skeletal muscle mass and function with age represents an important source of frailty and functional decline in the elderly. Antioxidants from botanical extracts have been shown to enhance the development, mass, and strength of skeletal muscle by influencing age-related cellular and molecular processes. Tannase-treated green tea extract contains high levels of the antioxidants (−)-epicatechin (EC) and gallic acid that may have therapeutic benefits for age-related muscle decline. The aim of this study was to investigate the effect of tannase-treated green tea extract on various muscle-related parameters, without concomitant exercise, in a single-center, randomized, double-blind, placebo-controlled study. Administration of tannase-treated green tea extract (600 mg/day) for 12 weeks significantly increased isokinetic flexor muscle and handgrip strength in the treatment group compared with those in the placebo (control) group. In addition, the control group showed a significant decrease in arm muscle mass after 12 weeks, whereas no significant change was observed in the treatment group. Blood serum levels of follistatin, myostatin, high-sensitivity C-reactive protein (hs-CRP), interleukin (IL)-6, IL-8, insulin-like growth factor-1 (IGF-1), and cortisol were analyzed, and the decrease in myostatin resulting from the administration of tannase-treated green tea extract was found to be related to the change in muscle mass and strength. In summary, oral administration of tannase-treated green tea extract containing antioxidants without concomitant exercise can improve muscle mass and strength and may have therapeutic benefits in age-related muscle function decline.

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.

Major determinants of circulating myostatin in polycystic ovary syndrome.

The present study was designed to investigate the possible impact of hormonal and demographic parameters of patients with polycystic ovary syndrome (PCOS) on the circulating levels of myostatin. The study cohort comprised 46 patients with PCOS and 42 healthy female controls, and all subjects were of normal weight. Multiple regression analysis was applied to investigate the possible associations between serum myostatin levels and other laboratory parameters. Evaluation of the levels of myostatin revealed no significant differences between the PCOS and control groups (P>0.05). In the control group, no significant correlations were identified between the myostatin levels and any other laboratory parameters. Only low-density-lipoprotein cholesterol (LDL-C) levels in the PCOS group were revealed to be significantly, although negatively, associated with myostatin levels (P=0.018). In the regression model of the PCOS group, an increase in LDL-C and prolactin (PRL) were associated with a decrease in myostatin (P=0.001 and P=0.013, respectively). Furthermore, a decrease in sex hormone-binding globulin (SHBG), fasting blood glucose (FBG) and monocytes were associated with an increase in myostatin (P=0.028, P<0.001 and P=0.026, respectively). An increase in triglycerides was also associated with an increase in myostatin (P=0.001). In the regression model of the control group, a decrease in LDL-C was associated with an increase in myostatin (P=0.003) and a decrease in thyroid-stimulating hormone was associated with a decrease in myostatin (P=0.028). These results indicated that the normal range of myostatin levels in patients with PCOS is regulated by changes in the circulating levels of PRL, LDL-C, SHBG, triglycerides, monocytes and FBG.

Isozygous and selectable marker-free MSTN knockout cloned pigs generated by the combined use of CRISPR/Cas9 and Cre/LoxP.

Predictable, clean genetic modification (GM) in livestock is important for reliable phenotyping and biosafety. Here we reported the generation of isozygous, functional myostatin (MSTN) knockout cloned pigs free of selectable marker gene (SMG) by CRISPR/Cas9 and Cre/LoxP. CRISPR/Cas9-mediated homologous recombination (HR) was exploited to knock out (KO) one allele of MSTN in pig primary cells. Cre recombinase was then used to excise the SMG with an efficiency of 82.7%. The SMG-free non-EGFP cells were isolated by flow cytometery and immediately used as donor nuclei for nuclear transfer. A total of 685 reconstructed embryos were transferred into three surrogates with one delivering two male live piglets. Molecular testing verified the mono-allelic MSTN KO and SMG deletion in these cloned pigs. Western blots showed approximately 50% decrease in MSTN and concurrent increased expression of myogenic genes in muscle. Histological examination revealed the enhanced myofiber quantity but myofiber size remained unaltered. Ultrasonic detection showed the increased longissimus muscle size and decreased backfat thickness. Precision editing of pig MSTN gene has generated isozygous, SMG-free MSTN KO cloned founders, which guaranteed a reliable route for elite livestock production and a strategy to minimize potential biological risks.

The effect of eight weeks resistance and aerobic training on myostatin and follistatin expression in cardiac muscle of rats.

Introduction: The clinical studies have shown that the myostatin gene expression and its serum density occur more frequently in heart patients than in healthy individuals. The purpose of this study is to investigate the influence of 8-week resistance and aerobic exercise on the myostatin and follistatin gene expression of myocardium muscle of healthy male Wistar rats. Methods: In this experimental study, 20 five-week-old adult Wistar rats (250 ± 26.5 g) were divided into three groups: healthy control group (n = 6), resistance exercise group (n = 7), and aerobic exercise group (n = 7). The resistance and aerobic exercise plan consisted of 8 weeks and 3 sessions per week. The resistance exercise group performed climbing a one-meter 26-stair ladder with a slope of 85 degrees for 3 sets of 5 repetitions per session. The aerobic exercise group performed running at a speed of 12 meters per minute for 30 minutes during the first sessions gradually increasing up to a speed of 30 meters per minute for 60 minutes during the final sessions (equivalent to 70% to 80% of maximum oxygen consumption). The differences between the groups were evaluated using a one-way analysis of variance (ANOVA) test. When appropriate, LSD post-hoc test was used. The significance level for the study was less than 0.05. Results: The results of this study shows that after 8 weeks of exercise, there is no significant difference between myostatin mRNA gene expression levels of the heart muscle among the three groups of control, resistance exercise, and aerobic exercise (P = 0.172, F = 1.953). However, the mean differences between follistatin mRNA levels of the heart muscle among the three groups of control, resistance exercise, and aerobic exercise are statistically significant (F = 38.022, P = 0.001). Furthermore, the ratio of follistatin to myostatin mRNA gene expression of the heart muscle (P = 0.001, F = 10.288) shows significant difference among the three groups. Conclusion: Our results indicate that the resistance and aerobic exercise could cause a decrease in myostatin and an increase in follistatin levels, thus preventing many muscular physiological disorders such as arthritis and muscle weakness.

Influence of rice whole-crop silage diet on growth performance, carcass and meat characteristics and muscle-related gene expression in Japanese Black steers.

The present study investigated the influence of a diet largely comprising rice whole-crop silage (rWCS) on growth performance, carcass and meat characteristics, and expression of genes involved in muscle growth of Japanese Black steers. Steers were randomly separated into rWCS-fed (rWCS ad libitum and restricted feeding of concentrate) and concentrate-fed groups. Total digestible nutrient intake and daily gain (DG) decreased in rWCS-fed steers in comparison with concentrate-fed steers, whereas dressed carcass weight and final body weight did not significantly differ between the groups. Decreases in drip loss in the muscle of rWCS-fed steers may be caused by α-tocopherol and β-carotene in muscle. Feeding large amounts of rWCS to steers may maintain quantitative productivity of beef steers equally to a concentrate-based diet, and improve the qualitative productivity. Results of gene expression suggest that activation of skeletal muscle growth in rWCS-fed steers may occur at the late fattening period owing to a decrease in myostatin and increase in myosin heavy chain gene expression. Preadipocyte factor-1 and myostatin genes may be strongly involved in the control of lipid accumulation. This rearing system would allow beef production to switch to rWCS-based diets from concentrate-based diets.

Overload-induced skeletal muscle hypertrophy is not impaired in STZ-diabetic rats.

The aim of this study was to evaluate the effect of overload-induced hypertrophy on extensor digitorum longus (EDL) and soleus muscles of streptozotocin-induced diabetic rats. The overload-induced hypertrophy and absolute tetanic and twitch forces increases in EDL and soleus muscles were not different between diabetic and control rats. Phospho-Akt and rpS6 contents were increased in EDL muscle after 7 days of overload and returned to the pre-overload values after 30 days. In the soleus muscle, the contents of total and phospho-Akt and total rpS6 were increased in both groups after 7 days. The contents of total Akt in controls and total rpS6 and phospho-Akt in the diabetic rats remained increased after 30 days. mRNA expression after 7 days of overload in the EDL muscle of control and diabetic animals showed an increase in MGF and follistatin and a decrease in myostatin and Axin2. The expression of FAK was increased and of MuRF-1 and atrogin-1 decreased only in the control group, whereas Ankrd2 expression was enhanced only in diabetic rats. In the soleus muscle caused similar changes in both groups: increase in FAK and MGF and decrease in Wnt7a, MuRF-1, atrogin-1, and myostatin. Differences between groups were observed only in the increased expression of follistatin in diabetic animals and decreased Ankrd2 expression in the control group. So, insulin deficiency does not impair the overload-induced hypertrophic response in soleus and EDL muscles. However, different mechanisms seem to be involved in the comparable hypertrophic responses of skeletal muscle in control and diabetic animals.

Postsurgical Acute Phase Reaction is Associated with Decreased Levels of Circulating Myostatin.

Muscle strength is of importance for postsurgical rehabilitation. Myostatin is a growth factor that regulates the size of muscles and could thus influence muscle mass and function in the postsurgical period. The aim of the present study was to study the changes in myostatin levels during the postsurgical inflammatory period. Myostatin was analysed in serum samples from two elective surgery groups, orthopaedic surgery (n = 24) and coronary bypass patients (n = 21). The samples were collected prior to surgery and 4 and 30days after surgery. In the orthopaedic group, the median myostatin levels decreased from 3582ng/L prior to surgery to 774ng/L at day 4 (p < 0.001) and to 2016ng/L at day 30 (p < 0.001). Median CRP increased from 2.35mg/L preoperatively to 117mg/L at day 4 and decreased to 5.5mg/L at day 30 in the same group. The coronary bypass group showed a similar pattern with a decrease in myostatin from 4212ng/L to 2574ng/L at day 4 (p < 0.001) and to 2808ng/L at day 30 (p = 0.002). Median CRP increased from 1.80mg/L preoperatively to 136mg/L at day 4 and returned to 6.12mg/L at day 30 in the coronary bypass group. There was a significant decrease in myostatin concentrations both in the early and late postsurgical period. The lowest myostatin concentration time point coincided with the highest CRP concentration time point.

Decrease in myostatin by ladder-climbing training is associated with insulin resistance in diet-induced obese rats.

Suppression of myostatin (MSTN) has been associated with skeletal muscle atrophy and insulin resistance (IR). However, few studies link MSTN suppression by ladder-climbing training (LCT) and IR. Therefore, we intended to identify the correlation with IR between LCT and to analyze the signaling pathways through which MSTN suppression by LCT regulates IR. The rats were randomly assigned to two types of diet: normal pellet diet (NPD, n = 8) and high-fat diet (HFD, n = 16). After 8 weeks, the HFD rats were randomly re-assigned to two groups (n = 8 for each group): HFD sedentary (HFD-S) and high-fat diet ladder-climbing training (HFD-LCT). HFD-LCT rats were assigned to LCT for 8 weeks. Western blotting, immunohistochemistry and enzyme assays were used to measure expression levels and activities of MSTN, GLUT4, PI3K, Akt and Akt-activated targets (mTOR, FoxO1 and GSK-3β). The LCT significantly improved IR and whole-body insulin sensitivity in HDF-fed rats. MSTN protein levels decreased in matching serum (42%, P = 0.007) and muscle samples (25%, P = 0.035) and its receptor mRNA expression also decreased (16%, P = 0.041) from obese rats after LCT. But the mRNA expression of insulin receptor had no obvious changes in LCT group compared with NPD and HFD-S groups (P = 0.074). The ladder-climbing training significantly enhanced PI3K activity (1.7-fold, P = 0.024) and Akt phosphorylation (83.3%, P = 0.022) in HFD-fed rats, significantly increased GLUT4 protein expression (84.5%, P = 0.036), enhanced phosphorylation of mTOR (4.8-fold, P < 0.001) and inhibited phosphorylation of FoxO1 (57.7%, P = 0.020), but did not affect the phosphorylation of GSK-3β. The LCT significantly reduced IR in diet-induced obese rats. MSTN may play an important role in regulating IR and fat accumulation by LCT via PI3K/Akt/mTOR and PI3K/Akt/FoxO1 signaling pathway in HFD-fed rats.

Effect of Indoor Concentrate Feeding vs. Outdoor Grazing on the Expression of Genes Involved in Muscle Growth and Nutrient Content in Japanese Black Steer Muscle

The objective of the present study was to investigate the effect of outdoor grazing on the expression of genes involved in muscle growth and the nutrient contents of skeletal muscle in steers. Ten Japanese Black steers were divided into two groups: grazing (GR) and concentrate (CT) groups. Crude protein, extractable lipid, moisture, fatty acid, cooking loss and Warner Bratzler shear force in muscle tissue were analyzed. The gene expression of myosin heavy chain (MyHC) isoform (2a, 2x and slow), myostatin, follistatin, peroxisome proliferator-activated receptor γ2 (PPARγ2), CCAAT/enhancer binding protein α (C/EBPα), heat shock protein (HSP) 27 and HSP40 in skeletal muscles was evaluated at the end of fattening. Decreases in MyHC-2a and MyHC-2x (fast-twitch fiber type) expression in the longissimus lumborum (LL) muscle were detected in the GR group compared with the CT group; in contrast, an increase in MyHC-slow (slow-twitch fiber type) expression was shown in the GR group. These results suggest that grazing initiated muscle fiber type conversion to slow-twitch from fast-twitch. A decrease in extractable lipid content was observed in the GR group in the LL and semitendinosus (ST) muscles. Crude protein content in the LL muscle in the GR group was higher than in the CT group. MyHC expression in LL muscle in the GR group was greater than in the CT group. A decrease in myostatin and PPARγ2 gene expression was detected in the GR group compared with the CT group in both muscles. Expression of C/EBPα in LL muscle in the GR group was lower than in the CT group. These results suggest that grazing steers at the end of fattening may lead to an increase in protein content and a decrease in fat accumulation in LL and/or ST muscles by regulation of myostatin, MyHC, PPARγ2 and C/EBPα gene expression.

Strength Training with Blood Flow Restriction Diminishes Myostatin Gene Expression

The aim of the study was to determine whether the similar muscle strength and hypertrophy responses observed after either low-intensity resistance exercise associated with moderate blood flow restriction or high-intensity resistance exercise are associated with similar changes in messenger RNA (mRNA) expression of selected genes involved in myostatin (MSTN) signaling. Twenty-nine physically active male subjects were divided into three groups: low-intensity (20% one-repetition maximum (1RM)) resistance training (LI) (n = 10), low-intensity resistance exercise associated with moderate blood flow restriction (LIR) (n = 10), and high-intensity (80% 1RM) resistance exercise (HI) (n = 9). All of the groups underwent an 8-wk training program. Maximal dynamic knee extension strength (1RM), quadriceps cross-sectional area (CSA), MSTN, follistatin-like related genes (follistatin (FLST), follistatin-like 3 (FLST-3)), activin IIb, growth and differentiation factor-associated serum protein 1 (GASP-1), and MAD-related protein (SMAD-7) mRNA gene expression were assessed before and after training. Knee extension 1RM significantly increased in all groups (LI = 20.7%, LIR = 40.1%, and HI = 36.2%). CSA increased in both the LIR and HI groups (6.3% and 6.1%, respectively). MSTN mRNA expression decreased in the LIR and HI groups (45% and 41%, respectively). There were no significant changes in activin IIb (P > 0.05). FLST and FLST-3 mRNA expression increased in all groups from pre- to posttest (P < 0.001). FLST-3 expression was significantly greater in the HI when compared with the LIR and LI groups at posttest (P = 0.024 and P = 0.018, respectively). GASP-1 and SMAD-7 gene expression significantly increased in both the LIR and HI groups. We concluded that LIR was able to induce gains in 1RM and quadriceps CSA similar to those observed after traditional HI. These responses may be related to the concomitant decrease in MSTN and increase in FLST isoforms, GASP-1, and SMAD-7 mRNA gene expression.

Muscular Hypertrophy and Changes in Cytokine Production After Eccentric Training in the Rat Skeletal Muscle

We investigated the time course effects of eccentric training on muscular size, strength, and growth factor/cytokine production by using an isokinetic-exercise system for rats. Male Wistar rats (n = 34) were randomly assigned into 4 groups: 5 session eccentric-training group (ECC5S, n = 10); 5 session sham-operated group (CON5S, n = 10); 10 session eccentric-training group (ECC10S, n = 7); 10 session sham-operated group (CON10S, n = 7). In each group, a session of either training or sham operation was performed every 2 days. The training consisted of 4 sets of forced dorsiflexion (5 repetitions) combined with electric stimulation of plantar flexors. The wet weight of medial gastrocnemius muscle did not increase significantly after 5 sessions of training, whereas that after 10 sessions of training significantly increased with a concomitant increase in the cross-sectional area (CSA) of muscle fibers (weight, p < 0.05; fiber CSA, p < 0.001). Interleukin (IL)-6 in ECC5S and ECC10S groups showed significant increases (p < 0.01), whereas those of tumor necrosis factor (TNF)-α and IL-10 did not. The phospho-stat-3 showed a significant increase in ECC10S (p < 0.001) but not in ECC5S. Myostatin and follistatin also showed significant differences only between ECC10S and CON10S (p < 0.05). The results showed that repeated sessions of eccentric training for 20 days cause increases in muscular size and strength associated with increases in IL-6, follistatin, phospho-stat-3, and a decrease in myostatin. The delayed responses of IL-6, myostatin, phospho-stat-3, and follistatin would be due to the chronic effects of repeated training and possibly important for muscular hypertrophy.

Acute Loading and Aging Effects on Myostatin Pathway Biomarkers in Human Skeletal Muscle After Three Sequential Bouts of Resistance Exercise

To determine the influence of age and resistance exercise on myostatin pathway-related genes, younger (n = 10; 28 ± 5 years) and older (n = 10; 68 ± 6 years) men underwent four testing conditions (T1-T4). A baseline (T1) muscle sample was obtained, whereas the second and third biopsies were obtained 48 hours following the first and second training sessions (T2, T3), and a final biopsy was taken 24 hours following T3. The training sessions consisted of 3 sets of 10 repetitions (80% of one repetition maximum) on leg press, hack squat, and leg extension exercises. Follistatin (FST) messenger RNA was greater in older compared with younger men at T1 and T2 (p < .05). Follistatin-like 3 (FSTL3) messenger RNA was greater in older compared with younger men at T1 and T4 (p < .05). In older men, there was a significant decrease in myostatin (MSTN) messenger RNA at T4 (p < .05). Older men contained less active (Ser-425 phosphorylated) SMAD3 (p-SMAD3) protein than younger men at T3 and T4 (p < .05).Although it is well known that younger individuals possess a greater hypertrophic potential to resistance exercise, it appears that older individuals may paradoxically possess a more favorable resistance exercise response regarding myostatin pathway-related genes and a protein marker of pathway activity. Future research is warranted to examine the physiological significance of this age-dependent mechanism.

Hypoxia during postnatal development results in systemic inflammation, growth retardation and extensive cardiac compensatory adaptation

Increasingly, hypoxia is viewed as an important disease mechanism in both childhood asthma and obesity. In children, hypoxia results in chronic inflammation. We investigated the potential of a neonatal rat hypoxia model (Hx) for the study of inflammation. Hypoxia (12% O2) during postnatal day 2 to 20, resulted in a profound decrement in growth similar to that seen in growth restriction (Gr) due to large liter size (Hx pups 47% smaller than control (NC). Hx animals exhibited a 40% increase in Tumor Necrosis Factor-α and a 2-fold increase in Interleukin-6, while circulating Growth Hormone, Insulin Like Growth Factor-I and Vascular Endothelial Growth Factor were depressed (57, 60, and 33% respectively). Despite this non-anabolic milieu, Hx pups demonstrated a remarkable set of compensatory adaptations not seen in Gr of a similar size. In Hx, the left & right ventricles (LV, RV) were 2.3-fold & 4.8-fold, larger than in NC (mg/g body). Contractile protein content in the RV was 2 fold higher and the expression of slow β-myosin heavy chain was increased 18 fold. Adaptive mechanisms appeared to include a decrease in myostatin (−3 fold, mRNA), miR1(−14%) and IGFBP5 (−42% mRNA) levels. These results indicate that local regulatory mechanisms can respond to functional demands in the face of dramatically decreased growth promoting signals and increased inflammatory components. Support - NIH P01HD048721