Serum Myostatin among Excessive Drinkers.

Myostatin acts as a negative regulator of muscle growth. Its effect on fat mass is subject to debate. Among alcoholics, there is a high prevalence of muscle atrophy, and increased fat deposition has been also described in these patients. Myostatin could be involved in these alterations, but its relationships with body composition have been scarcely studied in alcoholic patients. To analyze the behavior of myostatin among alcoholics and its relationship with alcohol intake, liver function, and body composition. We investigated serum myostatin in 59 male patients and 18 controls. Patients were all heavy drinkers admitted with organic complications related to excessive ethanol ingestion. Densitometry analysis was used to assess body composition in 46 patients. Handgrip was assessed in 51 patients. Patients showed lower myostatin values than controls (Z = 3.80; p < 0.001). There was a significant relationship between myostatin and fat at the right leg (ρ = 0.32; p = 0.028), left leg (ρ = 0.32; p = 0.028), trunk (ρ = 0.31, p = 0.038), total fat proport ion (ρ = 0.33, p = 0.026), and gynecoid fat distribution (ρ = 0.40, p = 0.006) but not with lean mass (total lean ρ = 0.07; p = 0.63; trunk lean ρ = 0.03; p = 0.85; lower limbs ρ = 0.08; p = 0.58; upper limbs ρ = 0.04 p = 0.82; android ρ = 0.02; p = 0.88, or gynoid lean mass ρ = 0.20; p = 0.19). In total, 80.43% of patients showed at least one criterion of osteosarcopenic adiposity (OSA). Myostatin was related to OSA obesity. We also observed higher myostatin values among patients with body mass index > 30 kg/m2. Serum myostatin was lower among excessive drinkers, and it was related to increased fat deposition among these patients but not to lean mass, handgrip, or bone mineral density.

Serum Myostatin and Follistatin Levels in Patients With Dermatomyositis and Polymyositis.

BACKGROUND: Myostatin is a protein in the TGF-ß family that negatively regulates muscle mass, and follistatin is a myostatin antagonist. OBJECTIVE: The aim of this study was to measure serum levels of myostatin and follistatin in idiopathic inflammatory myopathy patients and correlate these levels with muscle strength, fatigue, functional capacity, damage, and serum levels of muscle enzymes. METHODS: This was a multicenter cross-sectional study including 50 patients (34 dermatomyositis and 16 polymyositis [PM]) and 52 healthy individuals (control group [CG]). The disease status was evaluated according to the International Myositis Assessment & Clinical Studies. Fatigue was rated according to the Fatigue Severity Scale, and body composition was measured using dual-energy x-ray emission densitometry. Myostatin and follistatin were measured using enzyme-linked immunosorbent assays. RESULTS: Mean age was 50.9 ± 14.0 years, and mean disease duration was 89.2 ± 80.9 months. There were no differences in levels of myostatin (14.15 ± 9.65 vs. 10.97 ± 6.77 ng/mL; p = 0.131) or follistatin (0.53 ± 0.71 vs. 0.49 ± 0.60 ng/mL; p = 0.968) between patients and the CG. However, myostatin levels were higher in PM than CG (16.9 ± 12.1 vs. 11.0 ± 6.8 ng/mL; p = 0.036). There was no difference in serum myostatin among patients with and without low lean mass. Patients not treated with corticosteroids had higher serum levels of myostatin than the CG. There was a weak negative correlation between follistatin and Manual Muscle Testing and a Subset of Eight Muscles and a weak positive correlation between follistatin and Healthy Assessment Questionnaire. CONCLUSIONS: Serum levels of myostatin and follistatin did not differ between dermatomyositis and PM patients and control subjects. The assessment of serum levels of myostatin and follistatin in idiopathic inflammatory myopathy patients seems not to be helpful in clinical practice.

The role of GDF11 in aging and skeletal muscle, cardiac and bone homeostasis.

GDF11 is a secreted factor in the TGFß family of cytokines. Its nearest neighbor evolutionarily is myostatin, a factor discovered as being a negative regulator of skeletal muscle growth. High profile studies several years ago suggested that GDF11 declines with age, and that restoration of systemic GDF11 to 'youthful' levels is beneficial for several age-related conditions. Particularly surprising was a report that supplementation of GDF11 aided skeletal muscle regeneration, as its homolog, myostatin, has the opposite role. Given this apparent contradiction in functionality, multiple independent labs sought to discern differences between the two factors and better elucidate age-related changes in circulating GDF11, with most failing to reproduce the initial finding of declining GDF11 levels, and, importantly, all subsequent studies examining the effects of GDF11 on skeletal muscle described an inhibitory effect on regeneration - and that higher doses induce skeletal muscle atrophy and cachexia. There have also been several studies examining the effect of GDF11 and/or the downstream ActRII pathway on cardiac function, along with several interesting reports on bone. A review of the GDF11 literature, as it relates in particular to aging and skeletal muscle, cardiac and bone biology, is presented.

MOTS-c reduces myostatin and muscle atrophy signaling.

Obesity and type 2 diabetes are metabolic diseases, often associated with sarcopenia and muscle dysfunction. MOTS-c, a mitochondrial-derived peptide, acts as a systemic hormone and has been implicated in metabolic homeostasis. Although MOTS-c improves insulin sensitivity in skeletal muscle, whether MOTS-c impacts muscle atrophy is not known. Myostatin is a negative regulator of skeletal muscle mass and also one of the possible mediators of insulin resistance-induced skeletal muscle wasting. Interestingly, we found that plasma MOTS-c levels are inversely correlated with myostatin levels in human subjects. We further demonstrated that MOTS-c prevents palmitic acid-induced atrophy in differentiated C2C12 myotubes, whereas MOTS-c administration decreased myostatin levels in plasma in diet-induced obese mice. By elevating AKT phosphorylation, MOTS-c inhibits the activity of an upstream transcription factor for myostatin and other muscle wasting genes, FOXO1. MOTS-c increases mTORC2 and inhibits PTEN activity, which modulates AKT phosphorylation. Further upstream, MOTS-c increases CK2 activity, which leads to PTEN inhibition. These results suggest that through inhibition of myostatin, MOTS-c could be a potential therapy for insulin resistance-induced skeletal muscle atrophy as well as other muscle wasting phenotypes including sarcopenia.NEW & NOTEWORTHY MOTS-c, a mitochondrial-derived peptide reduces high-fat-diet-induced muscle atrophy signaling by reducing myostatin expression. The CK2-PTEN-mTORC2-AKT-FOXO1 pathways play key roles in MOTS-c action on myostatin expression.

Myostatin in combination with creatine phosphokinase or albumin may differentiate patients with cirrhosis and sarcopenia.

In patients with liver cirrhosis (LC), sarcopenia is correlated with frequent complications and increased mortality. Myostatin, a myokine, is a potential biomarker of skeletal mass and/or sarcopenia. The aim of this study was to examine the association between myostatin and muscle mass and evaluate myostatin as a biomarker of sarcopenia in LC. Skeletal muscle index (SMI) and myosteatosis were evaluated by computed tomography scan. Muscle quantity and quality along with muscle strength and function were used to diagnose sarcopenia. Serum myostatin was measured by ELISA. One hundred and fifteen consecutive patients with LC [72.2% male, median age 59 yr (IQR 52-67), MELD 12 (8-16), 28.7% with compensated LC] were included. Low SMI was diagnosed in 49.6% and sarcopenia in 34.8% (21.7% severe). Myostatin levels were lower in low (P < 0.001) compared with patients with normal SMI and were strongly correlated with SMI in MELD score ≥ 15 (r = 0.571, P < 0.001). Myostatin was also lower in patients with sarcopenia compared with those without (P < 0.001) and even lower in severe sarcopenia (P < 0.001). In multivariate analysis, myostatin, age, and albumin remained significant predictors of low SMI after adjustment for sex, MELD, and creatine phosphokinase (CPK). Similarly, myostatin and age predicted sarcopenia after adjustment for sex, MELD, CPK, and albumin. The ratios log10myostatin-to-CPK or albumin-to-myostatin were found to have acceptable diagnostic accuracy in ruling out sarcopenia in total patients. However, the best diagnostic performance was shown in MELD ≥ 15 (AUROC 0.829 or 0.801, respectively). Myostatin is independently associated with both skeletal muscle mass and sarcopenia. Myostatin in combination with CPK or albumin are good surrogate markers in excluding sarcopenia.NEW & NOTEWORTHY Serum levels of myostatin were significantly lower in cirrhotic patients with impaired skeletal mass index (SMI) and sarcopenia than those without. Serum levels of myostatin have a positive correlation with SMI. Myostatin levels are independently associated with sarcopenia, diagnosed according to the latest criteria, in patients with cirrhosis. Myostatin in combination with creatine phosphokinase or albumin have good accuracy excluding sarcopenia in patients with cirrhosis.

Identification of frailty and sarcopenia in hospitalised older people.

BACKGROUND: People with frailty and/or sarcopenia have an increased risk of negative health outcomes. However, their diagnosis is often difficult. Considering the potential value of myostatin and follistatin as biomarkers of these conditions, we aimed to compare the association between both myokines and frailty and/or sarcopenia in post-hospitalised older people. In addition, the capability of myostatin and follistatin for identifying frailty and sarcopenia was compared with physical tests. MATERIALS AND METHODS: Participants in this cross-sectional study consisted of 84 post-hospitalised patients immediately after discharge. Participants met the following inclusion criteria: aged ≥ 70 years, score of ≥20 on the Mini-Mental State Examination, and able to stand up and walk independently for at least 4 m. Serum myostatin and follistatin concentrations were measured by enzyme-linked immunosorbent assay. Body measures and results from 4 physical tests (hand grip, chair stand, 8-foot timed Up and Go (8TUG) and gait speed (GS)) were also recorded. Frailty was evaluated by the Fried index, and sarcopenia by the criteria of the European Working Group on Sarcopenia in Older People. RESULTS: Myostatin concentration was lower and follistatin concentration higher in people with frailty or sarcopenia. Receiver operating characteristic curves indicated that GS and 8TUG tests had the greatest capability for identifying frailty. Myostatin was the only variable capable of identifying sarcopenia. CONCLUSION: Myostatin may be a useful biomarker for sarcopenia in post-hospitalised older adults. However, it has a lower capability for identifying frailty than physical tests. Further studies using larger samples and these myokines together with other biomarkers are warranted.

Muscle mass and plasma myostatin after exercise training: a substudy of Renal Exercise (RENEXC)-a randomized controlled trial.

BACKGROUND: Sarcopenia increases as renal function declines and is associated with higher morbidity and mortality. Myostatin is a negative regulator of muscle growth. Its expression in response to exercise is unclear. In this prespecified substudy of the Renal Exercise (RENEXC) trial, we investigated the effects of 12 months of exercise training on sarcopenia, muscle mass and plasma myostatin and the relationships between physical performance, muscle mass and plasma myostatin. METHODS: A total of 151 non-dialysis-dependent patients (average measured glomerular filtration rate 23 ± 8 mL/min/1.73 m2), irrespective of age or comorbidity, were randomly assigned to either strength or balance in combination with endurance training. Body composition was measured with dual-energy X-ray absorptiometry. Plasma myostatin was analysed using enzyme-linked immunosorbent assay kits. RESULTS: After 12 months, the prevalence of sarcopenia was unchanged, leg and whole-body lean mass increased significantly in the balance group and was unchanged in the strength group. Whole fat mass decreased significantly in both groups. There were no significant between-group differences in sarcopenia or body composition. Plasma myostatin levels increased significantly in both groups, with a significant difference in favour of the strength group. Plasma myostatin was significantly positively related to muscle mass and physical performance at baseline, but these relationships were attenuated after 12 months. CONCLUSIONS: Exercise training seems to be effective in preventing sarcopenia and maintaining muscle mass in non-dialysis-dependent patients with chronic kidney disease (CKD). However, the role of plasma myostatin on muscle mass and physical performance in patients with CKD warrants further study.

Statins induce skeletal muscle atrophy via GGPP depletion-dependent myostatin overexpression in skeletal muscle and brown adipose tissue.

Myopathy is the major adverse effect of statins. However, the underlying mechanism of statin-induced skeletal muscle atrophy, one of statin-induced myopathy, remains to be elucidated. Myostatin is a negative regulator of skeletal muscle mass and functions. Whether myostatin is involved in statin-induced skeletal muscle atrophy remains unknown. In this study, we uncovered that simvastatin administration increased serum myostatin levels in mice. Inhibition of myostatin with follistatin, an antagonist of myostatin, improved simvastatin-induced skeletal muscle atrophy. Simvastatin induced myostatin expression not only in skeletal muscle but also in brown adipose tissue (BAT). Mechanistically, simvastatin inhibited the phosphorylation of forkhead box protein O1 (FOXO1) in C2C12 myotubes, promoting the nuclear translocation of FOXO1 and thereby stimulating the transcription of myostatin. In differentiated brown adipocytes, simvastatin promoted myostatin expression mainly by inhibiting the expression of interferon regulatory factor 4 (IRF4). Moreover, the stimulative effect of simvastatin on myostatin expression was blunted by geranylgeranyl diphosphate (GGPP) supplementation in both myotubes and brown adipocytes, suggesting that GGPP depletion was attributed to simvastatin-induced myostatin expression. Besides, the capacities of statins on stimulating myostatin expression were positively correlated with the lipophilicity of statins. Our findings provide new insights into statin-induced skeletal muscle atrophy. Graphical headlights 1. Simvastatin induces skeletal muscle atrophy via increasing serum myostatin levels in mice; 2. Simvastatin promotes myostatin expression in both skeletal muscle and brown adipose tissue through inhibiting GGPP production; 3. The stimulating effect of statins on myostatin expression is positively correlated with the lipophilicity of statins.

The relationship between changes in serum myostatin and adiponectin levels in patients with obesity undergoing a weight loss program.

BACKGROUND: An effective strategy for weight loss in patients who are overweight or obese is to reduce body fat mass while maintaining skeletal muscle mass. Adiponectin and myostatin are affected through changes in body composition due to weight loss, and examining their dynamics may contribute to strategies for maintaining skeletal muscle mass through weight loss. We aimed to examine the relationships among myostatin, adiponectin, and body composition, depending on the extent of weight loss, in patients with obesity undergoing a weight loss program. METHODS: We examined 66 patients with obesity (age: 46.8 ± 14.0 years, body mass index: 34.3 [31.0-38.4] kg/m2) attending a hospital weight loss program. We categorized the patients into two groups, namely an L group (those with a weight reduction of < 5% from baseline) and an M group (those with a weight reduction of > 5% from baseline). All patients underwent blood tests and were assessed for body composition, insulin resistance, adipocytokine and myokine levels, exercise tolerance, and muscle strength at baseline and post-intervention. RESULTS: Serum myostatin and adiponectin levels increased post-intervention in both groups. Body weight and %fat decreased, and the rate of lean body mass (%LBM) increased in both groups. Exercise capacity and muscle strength improved in the M group only. Change in (⊿) myostatin correlated with ⊿%fat, ⊿%LBM, and ⊿adiponectin. ⊿adiponectin (ß = - 0.262, p = 0.035) was an independent predictor of ⊿myostatin. CONCLUSIONS: Myostatin and adiponectin might cross-talk and regulate changes in skeletal muscle and fat mass with or without successful weight loss. These findings indicate that evaluating serum myostatin and adiponectin levels in clinical practice could be used to predict the effects of weight loss and help prevent skeletal muscle mass loss.

Changes in Serum Myostatin Levels in Alcoholic Hepatitis Correlate with Improvement in MELD.

BACKGROUND: Alcoholic hepatitis (AH) is a serious clinical syndrome often associated with muscle wasting. Myostatin, a member of the transforming growth factor-ß superfamily, has been studied in diseases with muscle wasting; however, the role of myostatin in AH is unknown. AIMS: To investigate the association between myostatin, clinical variables, and outcomes in AH. METHODS: We analyzed data for cases of AH and controls of heavy drinkers (HD) in TREAT001 (NCT02172898) with serum myostatin levels (AH: n = 131, HD: n = 124). We compared characteristics between the two groups at baseline, 30, and 90 days and explored correlations between myostatin and clinical variables. We then modeled the relationship of myostatin to other variables, including mortality. RESULTS: Baseline median myostatin was lower in AH compared to HD (males: 1.58 vs 3.06 ng/ml, p < 0.001; females: 0.84 vs 2.01 ng/ml, p < 0.001). In multivariable linear regression, bilirubin, WBC, and platelet count remained negatively correlated with myostatin in AH. AH females who died at 90 days had significantly lower myostatin, but in a multivariable logistic model with MELD and myostatin, only MELD remained significantly associated with 90-day mortality. During 1-year follow-up, AH cases (n = 30) demonstrated an increase in myostatin (mean, 1.73 ng/ml) which correlated with decreasing MELD scores (ρ = - 0.42, p = 0.01). CONCLUSIONS: Myostatin levels are significantly lower in AH compared to HD and are negatively correlated with total bilirubin, WBC, and platelet count. Myostatin increased as patients experienced decreases in MELD. Overall, myostatin demonstrated a dynamic relationship with AH outcomes and future studies are needed to understand the prognostic role of myostatin in AH.

Regulation of circulating CTRP-2/CTRP-9 and GDF-8/GDF-15 by intralipids and insulin in healthy control and polycystic ovary syndrome women following chronic exercise training.

BACKGROUND: Polycystic ovary syndrome (PCOS) is associated with obesity, diabetes, and insulin resistance. The circulating C1Q/TNF-related proteins (CTRP-2, CTRP-9) and growth differentiation factors (GDF-8, GDF-15) contribute to glucose and lipid homeostasis. The effects of intralipids and insulin infusion on CTRP-2, CTRP-9, GDF-8 and GDF-15 in PCOS and control subjects before and after chronic exercise training were examined. METHODS: Ten PCOS and nine healthy subjects were studied at baseline status and after moderate-intensity chronic exercise training (1 h exercise, 3 times per week, 8 weeks). All participants were infused with 1.5 mL/min of saline or intralipids (20%) for 5 h, and during the last 2 h of saline or intralipids infusion hyperinsulinemic-euglycemic clamp (HIEC) was performed. CTRP-2, CTRP-9, GDF-8 and GDF-15 levels were measured at 0, 3 and 5 h. RESULTS: Intralipids dramatically increased CTRP-2 levels in PCOS (P = 0.02) and control (P = 0.004) subjects, which was not affected by insulin infusion or by exercise. Intralipids alone had no effects on CTRP-9, GDF-8, or GDF-15. Insulin increased the levels of GDF-15 in control subjects (P = 0.05) during the saline study and in PCOS subjects (P = 0.04) during the intralipid infusion. Insulin suppressed CTRP9 levels during the intralipid study in both PCOS (P = 0.04) and control (P = 0.01) subjects. Exercise significantly reduced fasting GDF-8 levels in PCOS (P = 0.03) and control (P = 0.04) subjects; however, intralipids infusion after chronic exercise training increased GDF-8 levels in both PCOS (P = 0.003) and control (P = 0.05) subjects and insulin infusion during intralipid infusion reduced the rise of GDF-8 levels. CONCLUSION: This study showed that exogenous lipids modulate CTRP-2, which might have a physiological role in lipid metabolism. Since chronic exercise training reduced fasting GDF-8 levels; GDF-8 might have a role in humoral adaptation to exercise. GDF-15 and CTRP-9 levels are responsive to insulin, and thus they may play a role in insulin responses.

Combination of resistance and aerobic exercise for six months improves bone mass and physical function in HIV infected individuals: A randomized controlled trial.

To evaluate the effect of combined resistance and aerobic training (RT+AT) on regional bone mineral density (BMD) and physical performance in people living with HIV (PLWH). Forty PLWH (20 men and 20 women) were randomized into RT+AT group (n = 20; age = 38.3 ± 4.9) or non-exercise control group (n = 20; age = 37.9 ± 5.1). The RT+AT group was required to perform a nonlinear periodized resistance training program targeting large muscle groups followed by 20 min aerobic exercise at 65-80% of maximal heart rate. Participants in RT+AT performed three supervised sessions per week for 6-months, whereas participants in the control group were instructed to continue with their current lifestyle habits. The primary outcome was bone mineral density (lumbar spine (L2-L4), femoral neck, and distal 1/3 radius). Secondary outcomes included physical function, anthropometry, inflammatory markers, and growth factors. The RT+AT group demonstrated a significant increase in BMD at follow-up for the Lumbar spine (L2-L4), femoral neck, and 1/3 radius (all, P < .05), and There were no gender differences in the training response between men and women for any of the BMD regions. Similar findings were also observed for lean body mass, IGF1and Adiponectin (P < .001). We observed a decrease in percent body fat, fat mass, IL-6, TNF-α, and myostatin in the RT+AT group (P < .001). Finally, there was a significant increase in handgrip strength and gait speed for both women and men in the RT+AT group (P < .001). A combination of resistance and aerobic training appears to be a feasible and effective means for counteracting bone loss and improving various inflammatory markers, physical function, and growth hormones in PLWH.

Targeted Approach to Distinguish and Determine Absolute Levels of GDF8 and GDF11 in Mouse Serum.

Growth differentiation factor 11 (GDF11) is a TGF-ß superfamily circulating factor that regulates cardiomyocyte size in rodents, sharing 90% amino acid sequence identity in the active domains with myostatin (GDF8)-the major determinant of skeletal muscle mass. Conflicting data on age-related changes in circulating levels have been reported mainly due to the lack of specific detection methods. More recently, liquid chromatography tandem mass spectrometry (LC-MS/MS) based assay showed that the circulating levels of GDF11 do not change significantly throughout human lifespan, but GDF8 levels decrease with aging in men. Here a novel detection method is demonstrated based on parallel reaction monitoring LC-MS/MS assay combined with immunoprecipitation to reliably distinguish GDF11 and GDF8 as well as determine their endogenous levels in mouse serum. The data indicate that both GDF11 and GDF8 circulating levels significantly decline with aging in female mice.

Circulating Myostatin Levels Decrease Transiently after Implantation of a Hip Hemi-Arthroplasty.

INTRODUCTION: Muscle and bone metabolism are both important for the healing of fractures and the regeneration of injured muscle tissue. The aim of this investigation was to evaluate myostatin and other regulating factors in patients with hip fractures who underwent hemi-arthroplasty. METHODS: Serum levels of myostatin (MSTN), follistatin (FSTN), dickkopf-1 (Dkk1), and periostin (PSTN) as well as markers of bone turnover were evaluated in patients with hip fractures before surgery and twice in the 2 weeks after surgery. These parameters were also evaluated in age- and gender-matched subjects without major musculoskeletal injury. RESULTS: MSTN was transiently reduced; its opponent FSTN was transiently increased. Dkk1, the negative regulator of bone mass, and PSTN, a marker of subperiosteal bone formation, increased after surgery. With regard to markers of bone turnover, resorption was elevated during the entire period of observation whereas the early bone formation marker N-terminal propeptide of type I collagen was elevated 12 days after surgery. CONCLUSIONS: Unexpectedly, MSTN, a negative regulator of muscle growth, was reduced after surgery compared with before surgery. As musculoskeletal markers are altered during bone healing, they do not reflect general bone metabolism after fracture or joint arthroplasty. This is important because many elderly patients receive treatment for osteoporosis.

Effects of Vibration Training in Interstitial Lung Diseases: A Randomized Controlled Trial.

BACKGROUND: Numerous studies have reported positive effects of exercise training in patients with interstitial lung disease (ILD) on physical capacity and quality of life. However, evidence is rare on the effects of specific forms of training and further pathophysiological mechanisms in these patients. OBJECTIVES: In this multicenter study we aimed to explore the clinical effects of whole-body vibration training (WBVT) in patients with ILD on various outcome measures, including proinflammatory cytokines and myostatin. METHODS: We randomly assigned 26 patients with different forms of multidisciplinary confirmed fibrotic ILDs either to the WBVT group (n = 11; 55% male, 61 ± 14 years old, forced vital capacity 83.2 ± 29.3% predicted, 6-min walking distance [6MWD] 478 ± 79 m) performing 3 months of a standardized training (3 times per week), or to a control training group (CTG, n = 15; 60% male, 63 ± 9 years old, FVC 74.6 ± 20.5% predicted, 6MWD 455 ± 85 m) performing sham WBV training. Training in the two groups was performed on a GalileoTM vibration plate (6-20 vs. 5 Hz). The functional assessments before and after the intervention period included pulmonary function, 6MWD test, chair rise test, ultrasonographic measurement of quadriceps muscle thickness (cross-sectional area), quality of life questionnaires, and serum samples. RESULTS: We observed a significant increase in 6MWD (∆Training = 30 m [12-67], p = 0.024) and a decrease of myostatin (∆Training = -465 pg/mL [-713 to -166], p = 0.008) in the WBVT group. In contrast, no significant differences were observed in the CTG. CONCLUSIONS: The present study demonstrates that WBVT is able to significantly increase 6MWD and decrease myostatin in patients with fibrotic ILDs. Therefore, WBVT seems to be a beneficial and feasible training modality in ILD patients. Clinical Trial Registry: German Clinical Trials Registry (DRKS00012930).

Regulatory aspects of myogenic factors GDF-8 and Follistatin on the intake of combined oral contraceptives.

Combined oral contraceptives are one of the most prescribed drugs in the western world. While there is little evidence regarding effects of estrogen or gestagens on muscle metabolism, androgens are well-known for their anabolic characteristics. In this study, we seeked to investigate potential correlations of the myokines GDF-8, IGF-1 and Follistatin with female sexual hormones and likewise possible interactions with combined oral contraceptives (Dienogest and Ethyl Estradiol) intake. We obtained serum samples of young healthy women to measure hormone correlations. Furthermore, we simulated combined oral contraceptive blood circulating hormone concentrations to identify myogenic effects on HSkM in vitro. GDF-8, IGF-1 and Follistatin showed concentration correlations (p = .005) in overall patients' serum, while Follistatin as a promyogenic protein additionally showed a positive correlation with testosterone and estradiol (p < .05). Lower GDF-8 levels were also linked to a higher BMI (p = .009). Upon combined oral contraceptives (COC) intake, patients showed decreased GDF-8 (p = .006) but increased Follistatin (p = .0001) concentrations compared to patients without COC intake. In vitro, addition of Ethyl Estradiol and Dienogest to HSkM cells revealed a pro-myogenic, proliferative, chemosensitized pattern. Our data support a pro-myogenic effect of combined oral contraceptives.

Myostatin as a potential biomarker to monitor sarcopenia in hip fracture patients undergoing a multidisciplinary rehabilitation and nutritional treatment: a preliminary study.

Hip fractures are the most common osteoporotic fractures related to disability in older adults, requiring surgery and a subsequent rehabilitation treatment. Sarcopenia is currently considered as a predictive of worse outcome in hip fracture patients and myostatin has been recently proposed a potential biomarker of this condition. Twenty hip fracture patients after total hip replacement (mean aged 75.9 ± 2.4 years) were randomly divided into two groups of ten subjects (groups A and B). Both groups performed a rehabilitation program (5 sessions of 40 min/week for 2 weeks, followed by home-based exercise protocol). Group A received also 2-month amino acid supplementation. Serum myostatin levels significantly decreased after 2 months in both group A (p = 0.01) and group B (p = 0.03) in sarcopenic patients only in group A (p = 0.04). These results suggest that myostatin might be considered a promising biomarker of sarcopenia in hip fracture older adults' patients undergoing rehabilitation and amino acid supplementation.

Relationship between serum level of growth differentiation factors 8, 11 and bone mineral density in girls with anorexia nervosa.

BACKGROUND: Adolescents with anorexia nervosa (AN) have low body mass and low bone mineral density (BMD). Growth differentiation factor 8 (Myostatin, GDF8) and its homologue growth differentiation factor 11 (GDF11), members of the TGF-ß super-family, play an important role in muscle regeneration and bone metabolism in healthy individuals. However, their association with BMD in AN is unknown. The present study was undertaken to investigate the relationship between GDF8, GDF11 and BMD in adolescent girls with AN. METHODS: Serum GDF8, GDF11 and BMD were determined in 25 girls (12-16 years old) with AN and 31 healthy girls (12-16 years old). RESULTS: Growth differentiation factor 8 levels were lower in AN subjects. On the contrary, GDF11 levels were higher in AN subjects than controls. There was no relationship between GDF8 and BMD. A significant negative correlation between GDF11 and BMD was found. In multiple linear stepwise regression analysis, BMI, 25-hydroxyvitamin D, GDF11, or lean mass, but not fat mass and GDF8, were independent predictors of BMD in the AN and control groups separately. CONCLUSIONS: Growth differentiation factor 11 was independent predictor of BMD in girls with AN. It suggested that GDF11 exerts a negative effect on bone mass.

Serum Myostatin Levels Are Higher in Fitter, More Active, and Non-Frail Long-Term Nursing Home Residents and Increase after a Physical Exercise Intervention.

BACKGROUND: Myostatin has been proposed as a candidate biomarker for frailty and sarcopenia. However, the relationship of myostatin with these conditions remains inconclusive. OBJECTIVE: To determine the association of serum myostatin concentration with body composition, physical fitness, physical activity level, and frailty in long-term nursing home residents. We also aimed to ascertain the effect of an exercise program on myostatin levels. METHODS: We obtained study data on 112 participants from long-term nursing homes. Participants were randomly assigned to a control or an intervention group and performed a 6-month multicomponent exercise program. Serum myostatin levels were analyzed by ELISA. Assessments also included body composition (anthropometry and bioelectrical impedance), physical fitness (Senior Fitness Test), physical activity level (accelerometry), and frailty (Fried frailty criteria, Clinical Frailty Scale, and Tilburg frailty indicator). RESULTS: The concentration of myostatin at baseline was positively correlated with: a leaner body composition (p < 0.05), and a higher number of steps per day and light and moderate-vigorous physical activity in women (p < 0.005); greater upper and lower limb strength, endurance, and poorer flexibility (p < 0.05) in men; and better performance (less time) in the 8-ft timed up-and-go test in both women (p < 0.01) and men (p < 0.005). We observed higher concentrations of serum myostatin in non-frail than in frail participants (p < 0.05). Additionally, we found that the implemented physical exercise intervention, which was effective to improve physical fitness, increased myostatin concentration in men (p < 0.05) but not in women. The improvements in physical condition were related with increases in serum myostatin only in men (p < 0.05-0.01). CONCLUSIONS: Higher serum levels of myostatin were found to be associated with better physical fitness. The improvements in physical fitness after the intervention were positively related to increases in myostatin concentrations in men. These results seem to rule out the idea that high serum myostatin levels are indicative of frailty in long-term nursing home residents. However, although the direction of association was opposite to that expected for the function of myostatin, the use of this protein as a biomarker for physical fitness, rather than frailty, merits further study.

Significance of serum Myostatin in hemodialysis patients.

BACKGROUND: Malnutrition and muscle wasting are common in haemodialysis (HD) patients. Their pathogenesis is complex and involves many molecules including Myostatin (Mstn), which acts as a negative regulator of skeletal muscle. The characterisation of Mstn as a biomarker of malnutrition could be useful in the prevention and management of this condition. Previous studies have reported no conclusive results on the actual relationship between serum Mstn and wasting and malnutrition. So, in this study, we evaluated Mstn profile in a cohort of regular HD patients. METHODS: We performed a cross-sectional study, enrolling 37 patients undergoing bicarbonate-HD (BHD) or haemodiafiltration (HDF) at least for six months. 20 sex-matched healthy subjects comprised the control group. Mstn serum levels were evaluated by ELISA before and after HD. We collected clinical and biochemical data, evaluated insulin resistance, body composition, malnutrition [by Malnutrition Inflammation Score (MIS)] and tested muscle function (by hand-grip strength, six-minute walking test and a questionnaire on fatigue). RESULTS: Mstn levels were not significantly different between HD patients and controls (4.7 ± 2.8 vs 4.5 ± 1.3 ng/ml). In addition, while a decrease in Mstn was observed after HD treatment, there were no differences between BHD and HDF. In whole group of HD patients Mstn was positively correlated with muscle mass (r = 0.82, p < 0.001) and inversely correlated with age (r = - 0.63, p < 0.01) and MIS (r = - 0.39, p = 0.01). No correlations were found between Mstn and insulin resistance, such as between Mstn levels and parameters of muscle strength and fatigue. In multivariate analysis, Mstn resulted inversely correlated with fat body content (ß = - 1.055, p = 0.002). CONCLUSIONS: Circulating Mstn is related to muscle mass and nutritional status in HD patients, suggesting that it may have a role in the regulation of skeletal muscle and metabolic processes. However, also considering the lack of difference of serum Mstn between healthy controls and HD patients and the absence of correlations with muscle function tests, our findings do not support the use of circulating Mstn as a biomarker of muscle wasting and malnutrition in HD.