Serum Myostatin Levels Research Articles

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.

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.

DMD CLINICAL THERAPIES I: P.123A randomized, placebo-controlled, double-blind, phase 1b/2 study of the novel anti-myostatin adnectin RG6206 (BMS-986089) in ambulatory boys with Duchenne muscular dystrophy

Inhibition of myostatin, a negative regulator of muscle growth, has been shown to increase skeletal muscle mass in several species. RG6206 (BMS-986089) is a potent, novel anti-myostatin adnectin shown to inhibit myostatin activity in healthy adults. This phase 1b/2 study (NCT02515669) assessed the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics of RG6206 in ambulatory boys with Duchenne muscular dystrophy (DMD). Forty-three ambulatory boys with DMD, aged 5-10, were randomized to receive weekly subcutaneous RG6206 (4-50 mg) or placebo. The primary endpoint was safety and tolerability over 24 weeks. Secondary endpoints were PK of RG6206, frequency of anti-drug antibodies (ADAs), effect on serum myostatin levels and MRI imaging. Exploratory outcomes included 4-stair climb velocity (4SC), 6-minute walk test distance (6MWT) and DXA imaging. No clinically significant changes in laboratory values, vital signs or ECG parameters were observed. Adverse events (AEs) were mostly mild; the most common drug-related AE was mild-to-moderate cutaneous injection site reactions (n=7, 21.9%). ADAs were observed in one patient, who had a positive titer at baseline with no post-treatment boost. RG6206 serum concentrations increased with dose and were accompanied by dose-dependent reduction in free myostatin at all dose levels. RG6206 was well tolerated. DXA imaging data showed increased lean body mass with RG6206 treatment vs. placebo. MRI imaging of the right thigh suggested that RG6206 had positive effects on muscle composition, with an increase in contractile, and lesser increase in non-contractile, tissue compared with placebo. However, this response did not appear to be dose dependent. Post hoc analyses of the correlation between MRI/DXA imaging data and functional measures including 4SC and 6MWT will be presented. An ongoing 48-week open-label phase of this study and a Phase 2/3 study will further evaluate RG6206 in ambulatory boys with DMD (NCT03039686).

The association between sarcopenia and decorin, an exercise‐induced myokine, in patients with liver cirrhosis: a pilot study

AbstractBackgroundSarcopenia frequently occurs in patients with liver cirrhosis (LC). The skeletal muscles secrete myokines, including myostatin, irisin, and decorin, which regulate skeletal muscle mass. This study aimed to investigate the association between myokine levels and muscle mass and to identify independent factors for muscle mass in patients with LC.Methods and ResultsThirty‐nine patients with LC were enrolled in this study (mean age, 75 years [41–84], female/male, 19/20) and were classified into muscle atrophy or non‐atrophy groups according to the Japan Society of Hepatology guidelines. Serum levels of myostatin, irisin, and decorin were measured by ELISA/EIA. Independent factors associated with skeletal muscle index (SMI) were investigated. Profiles associated with non‐atrophic muscle were determined by a decision‐tree analysis. There were no significant differences in body mass index (BMI) or blood ammonia or myostatin levels between the muscle atrophy and non‐atrophy groups. However, serum decorin and irisin levels were significantly higher in the non‐atrophy group than the atrophy group (11,888±5,418 vs. 5,642±1,978 pg/mL, P=0.0394; 35.1±1.9 vs. 31.1±8.3 ng/mL, P=0.0109). BMI and serum decorin level were identified as independent factors associated with SMI (P=0.0121, P=0.0483). In the decision‐tree analysis, serum decorin level was identified as the first divergence variable for non‐atrophic muscle. Of the patients with ≥10,226.8 pg/mL of decorin, 75% were in the non‐atrophy group.ConclusionsSerum decorin level was significantly associated with skeletal muscle mass and was an independent factor for skeletal muscle non‐atrophy in patients with LC. Decorin may be an important myokine regulating sarcopenia in patients with LC

Role of serum myostatin in the association between hyperinsulinemia and muscle atrophy in Japanese obese patients

AimsThe protein myostatin is a member of the transforming growth factor β superfamily. This is mainly expressed in skeletal muscle and negatively regulates skeletal muscle growth. The present study aimed to elucidate the associations among circulating myostatin level, skeletal muscle mass, and metabolic profiles in Japanese obese patients. MethodsJapanese obese outpatients (n = 74) were enrolled. We measured clinical parameters, quantified serum myostatin levels, and examined their associations in a cross-sectional manner. ResultsBoth total skeletal muscle mass and serum myostatin level were higher in males than in females. Among 74 patients, serum myostatin level was positively correlated with skeletal muscle mass and serum immunoreactive insulin (IRI) level [correlation coefficient (r) = 0.294, P = 0.011; r = 0.262, P = 0.024, respectively]. Furthermore, multivariate linear regression analysis revealed that serum myostatin level was positively correlated with IRI after adjusting for gender and skeletal muscle mass (β-coefficient = 0.230, P = 0.029, R2 = 0.236). ConclusionsIn obese patients, serum myostatin level was elevated in conjunction with an increase in IRI level independent of skeletal muscle mass. This may imply possible novel pathological implications of serum myostatin in muscle mass and metabolism in obese patients with hyperinsulinemia.

Healthy community-living older men differ from women in associations between myostatin levels and skeletal muscle mass.

BackgroundMyostatin is a negative regulator of muscle growth but the relationship between serum myostatin levels and muscle mass is unclear. This study investigated the association between serum myostatin levels and skeletal muscle mass among healthy older community residents in Taiwan, to evaluate the potential of serum myostatin as a biomarker for diagnosing sarcopenia and/or evaluating the effect of its treatment.MethodsStudy data were excerpted from a random subsample of the I‐Lan Longitudinal Aging Study population. Serum myostatin levels were determined and categorized into tertiles (low, medium, high). Relative appendicular skeletal muscle mass (RASM) was calculated as appendicular lean body mass by dual‐energy X‐ray absorptiometry divided by height squared (kg/m2). Low muscle mass was defined as recommended by the Asian Working Group for Sarcopenia.ResultsThe analytic study sample comprised 463 adults (mean age: 69.1 years; 49.5% men). Compared with subjects with normal RASM, those with lower RASM were older and frailer, with significantly higher prevalence of malnutrition, lower serum dehydroepiandrosterone (DHEA) levels, and were more likely to have low serum myostatin status. Multivariable logistic regression analysis showed that male sex (OR 3.60, 95% CI 1.30–9.92), malnutrition (OR 4.39, 95% CI 1.56–12.36), DHEA (OR 0.99, 95% CI 0.99–1.00), and low myostatin (OR 3.23, 95% CI 1.49–7.01) were all independent risk factors for low RASM (all P < 0.05). In men, DHEA (OR 0.99, 95% CI 0.98–1.00) and low myostatin (OR 4.89, 95% CI 1.79–13.37) were significantly associated with low RASM (both P < 0.05); however, only malnutrition was associated with low RASM in women (OR 13.59, 95% CI 2.22–83.25, P < 0.05).ConclusionsAmong healthy community‐living older adults, low serum myostatin levels were associated with low skeletal muscle mass in men, but not in women. Our results do not support using serum myostatin levels to diagnose sarcopenia, or to monitor how it responds to treatments. Further research is needed to understand why men apparently differ from women in the interrelationship between their myostatin levels and muscle mass.

Differential response of adipose tissue gene and protein expressions to 4- and 8-week administration of β-guanidinopropionic acid in mice.

β‐Guanidinopropionic acid (β‐GPA) feeding inhibits growth‐associated gain of body mass. It remains unknown, however, whether and how β‐GPA feeding affects growth‐associated increase in white adipose tissue (WAT) mass. We examined the effects of 4‐ and 8‐week β‐GPA feeding on serum myostatin levels and expression of genes and proteins related to adipogenesis, lipolysis, and liposynthesis in epididymal WAT (eWAT) and brown adipose tissue (BAT) in 3‐week‐old, juvenile male mice. Body, eWAT, and muscle weights were significantly lower in β‐GPA‐fed mice than in controls after feeding. Four‐ but not 8‐week‐β‐GPA feeding increased the serum myostatin level. Incubation of C2C12 myotubes with β‐GPA (1 mM) significantly promoted myostatin mRNA expression. The protein expression of peroxisome proliferator‐activated receptor gamma coactivator 1 α (PGC‐1α) and peroxisome proliferator‐activated receptor α (PPAR α) was up‐regulated in GPAF eWAT at week 4, but down‐regulated at week 8. There was no significant difference in the protein expression of adipocyte triglyceride lipase (ATGL), hormone‐sensitive lipase (HSL), fatty acid synthase (FAS), and acetyl‐CoA carboxylase (ACC) between groups in eWAT. In BAT, no significant difference was found in the protein expression of PGC‐1α, PPAR α, ATGL, and HSL between β‐GPA‐fed and control mice, whereas that of FAS and ACC was significantly lower in β‐GPA‐fed mice at week 8. Uncoupling protein 1 was expressed higher in β‐GPA‐fed mice both at weeks 4 and 8 than that in controls. Thus, the mechanism by which β‐GPA feeding in early juvenile mice inhibits growth‐associated increase in eWAT mass may differ between early and later periods of growth.

Evaluation of the relationship between muscle mass and serum myostatin levels in chronic hemodialysis patients.

The loss of muscle mass and cachexia is commonly seen in hemodialysis (HD) patients and contribute to morbidity and mortality. The exact mechanism of this fact is multifactorial and still unclear. Myostatin, a transforming growth factor-ß family ligand, is released from the skeletal and heart muscle and may be responsible for muscle degradation and atrophy. The aim of this study is evaluation of the relationship between muscle mass and serum myostatin level in chronic HD patients. One hundred and forty HD patients (79 males, 28 diabetic, mean age; 53.96 ± 13.6) were included in this cross-sectional study. Muscle mass measurement was made with dual energy-X ray absorptiometry. Appendicular skeletal muscle index (ASMI) was used as a muscle mass indicator. The anthropometric and biochemistry data were obtained. Serum myostatin levels were determined by an ELISA kit. Serum myostatin levels were elevated when compared to controls (P <0.001), but no significant correlation with ASMI was observed (P = 0.624). ASMI significantly correlated with serum creatinine (P <0.001), creatine phosphokinase (P <0.001), prealbumin (P <0.012), albumin (P <0.039), transferrin (P <0.001), phosphorus (P <0.001), Ca×P (P <0.012), inversely with Kt/V (P <0.001); not with BUN (P = 0.739), parathyroid hormone (P = 0.698), 25-hydroxyvitamin D (P = 0.603), bicarbonate (P = 0.062); such that these parameters also have influence on muscle mass regulation. Our study indicated that myostatin levels were high in HD patients but had no relation with ASMI. Myostatin is a well-known regulator of muscle mass so further studies are needed to demonstrate possible relationship.

Combining Amino Acid and Vitamin D Supplementation with Exercise Training Increases Skeletal Muscle Mass and Prevent Bone Mineral Density Loss in Participants with Low Muscle Mass

This study evaluated the impact of exercise training with amino acid and vitamin D supplementation on muscle and bone mass in participants with low muscle volume. Twenty-nine Japanese participants (56-84 years old) were enrolled and assigned into the supplement (n=15) and non-supplement (n=14) groups. All participants underwent a 6-month exercise program. Supplements and nutrition support were provided to the participants in the supplement group for 12 weeks. Body composition and whole bone mineral density (BMD) were measured using dual energy x-ray absorptiometry. The outcomes, including body composition, whole BMD, and skeletal muscle mass index (SMI), were evaluated twice: pre- and post-intervention. The SMI was 6.51(6.28; 7.14) and 5.58 (5.24; 6.05) (kg/m2) in men and women, respectively. The average SMI change was 0.13% (-0.05%; 0.31%) and 2.33% (-0.88%; 5.48%); [mean (lower; upper quartile)]. The average BMD loss in the non-supplement group was -2.78%, and the BMD increased in the supplement group by 4.34%; there was an absolute difference between the two groups (p&lt;0.05). After the intervention, serum myostatin was changed (p=0.001, non-supplement&gt;supplement), serum vitamin D was increased (p=0.03; supplement&gt;non-supplement), and BMD was maintained (p=0.03, supplement&gt;non-supplement). There was a significant difference in the serum myostatin level at baseline and at 6-month in the non-supplement group, with a mean difference of 483.78 ng/ml (p=0.01). There was no significant improvement in the total lean mass, and handgrip strength. Resistance exercise combined with an amino acid supplement affects muscle and bone mass in the short-term intervention.

Elevated serum myostatin level is associated with worse survival in patients with liver cirrhosis.

BackgroundWe aimed to elucidate the relationship between serum myostatin levels and other markers including skeletal muscle mass and to investigate the influence of serum myostatin levels on survival for patients with liver cirrhosis (LC).MethodsA total of 198 LC subjects were analysed in this study. Myostatin levels were measured using stored sera. We retrospectively investigated the relationship between myostatin level and other markers, and the influence of myostatin level on overall survival (OS). Assessment of skeletal muscle mass was performed using the psoas muscle index (PMI) on computed tomography images at baseline. PMI indicates the sum of bilateral psoas muscle mass calculated by hand tracing at the lumber three level on computed tomography images divided by height squared (cm2/m2). The study cohort was divided into two groups based on the median myostatin value in each gender.ResultsOur study cohort included 108 male and 90 female patients with a median age of 67.5 years. The median (range) myostatin level for male patients was 3419.6 pg/mL (578.4–12897.7 pg/mL), whereas that for female patients was 2662.4 pg/mL (710.4–8782.0 pg/mL) (P = 0.0024). Median (range) serum myostatin level for Child–Pugh A patients (n = 123) was 2726.0 pg/mL (578.4–12667.2 pg/mL), whereas that for Child–Pugh B or C patients (n = 75) was 3615.2 pg/mL (663.3–12897.7 pg/mL) (P = 0.0011). For the entire cohort, the 1‐, 3‐, 5‐, and 7‐year cumulative OS rates were 93.94%, 72.71%, 50.37%, and 38.47%, respectively, in the high‐myostatin group and 96.97%, 83.27%, 73.60%, and 69.95%, respectively, in the low‐myostatin group (P = 0.0001). After excluding hepatocellular carcinoma patients (at baseline) from our analysis (n = 158), the 1‐, 3‐, 5‐, and 7‐year cumulative OS rates were 96.0%, 77.93%, 52.97%, and 39.08%, respectively, in the high‐myostatin group and 96.39%, 87.58%, 77.63%, and 73.24%, respectively, in the low‐myostatin group (P = 0.0005). Higher age (P = 0.0111) and lower PMI (P < 0.0001) were identified as significant predictors of poorer OS in our multivariate analysis, while higher serum myostatin (P = 0.0855) tended to be a significant adverse predictor. In both genders, PMI, serum albumin, prothrombin time, and branched‐chain amino acid to tyrosine ratio showed a significantly inverse correlation with myostatin levels, and serum ammonia levels showed a significantly positive correlation with myostatin levels.ConclusionsHigher serum myostatin levels correlated with muscle mass loss, hyperammonemia, and impaired protein synthesis, as reflected by lower serum albumin levels and lower branched‐chain amino acid to tyrosine ratio levels. High serum myostatin levels were also associated with a reduced OS rate in LC patients.

Benefits of High-Intensity Exercise Training to Patients with Chronic Obstructive Pulmonary Disease: A Controlled Study

Background: Various exercise training programs are used for patients with chronic obstructive pulmonary disease (COPD) of different severity. Objectives: To investigate the impact of individualized high-intensity training on exercise capacity with COPD. Methods: A total of 49 patients agreed to participate. Of these, 31 were assigned to the training group and 18 served as controls. The training group exercised twice a week for 90 min with consecutively increasing loads. At the time of enrollment (T₀), as well as after 3 (T₁) and 6 (T₂) months, a 6-min walk test (6-MWT) was performed and data on health-related quality of life, femoral muscle thickness, and various serum markers were obtained. Results: The training group improved in their 6-MWT results (T₀ = 407 ± 152 m vs. T₁ = 459 ± 127 m, p = 0.002, vs. T₂ = 483.2 ± 130.1 m, p = 0.004), in their cross-sectional area of the musculus rectus femoris (T₀ = 6.2 ± 1.2 cm² vs. T₁ = 6.9 ± 1.2 cm², p = 0.003, vs. 7.5 ± 1.6 cm², p = 0.002), and in their St. George's Respiratory Questionnaire (SGRQ) score (T₀ = 43.3 ± 18.0 vs. T₁ = 36.0 ± 18.4, p = 0.001, vs. T₂ = 34.7 ± 18. 0, p = 0.004). Serum levels of myostatin, irisin, resistin, and α-Klotho did not change significantly within the training period. Of note, the exercise group showed an inverse relationship between serum levels of resistin and those of α-Klotho after 6 months (r = -0.608, p = 0.021). Conclusions: COPD patients undergoing an individualized, structured, high-intensity training program improved their exercise capacity, gained muscle mass, and improved their quality of life.

Changes in Lean Mass and Serum Myostatin with Habitual Protein Intake and High-Velocity Resistance Training.

Examine the associations between dietary protein intake, lean mass (LM), and serum myostatin (Mstn) levels among community-dwelling older adults participating in a 20-week high-velocity resistance training (HVRT) program. This longitudinal study consisted of 33 community-dwelling, older adults (mean age 77.0 years, SD = 6.4); all of which obtained physician clearance prior to study participation. Twenty-five females and eight males were randomized to a control (CON) or HVRT group. Anthropometric measures were obtained via dual energy x-ray absorptiometry (DXA) and peripheral venous blood draw used for serum myostatin analysis. Exercise was performed twice per week for 20 consecutive weeks. Food intake estimation with a diet history questionnaire (DHQ) was used for protein intake comparison to the recommended dietary allowance (RDA). All measures were recorded both prior to and following study participation. Altogether, protein was consumed in amounts more generous (1.01 ± 0.47 g·kg-1·d-1) than that of the RDA (0.8 g·kg-1·d-1). As a result of significant LM differences among men and women (p < 0.01), additional data were analyzed specific to sex. Serum myostatin was greater among females (6681.8 ± 3155.0 pg·mL-1) than males (5560.0 ± 2946.1 pg·mL-1); however, these values were not significantly different (p = 0.39). Combined, protein consumption and serum myostatin did not significantly influence LM among males (p = 0.09) or females (p = 0.71). Irrespective of training group, significant changes were not exhibited in dietary intake patterns, LM, or serum myostatin. Contrary to the proposed hypothesis, results suggest protein consumption and circulating serum myostatin levels did not significantly influence LM among older adults. Although HVRT positively impacts LM, neither exercise group displayed significant changes in LM. Therefore, further research is needed examining dietary intake, exercise modality, and myostatin downregulation as non-pharmacological approaches to combating sarcopenia.

Modulation of Myostatin/Hepatocyte Growth Factor Balance by Different Hemodialysis Modalities.

Background. In this study we investigated the relevance of myostatin and Hepatocyte Growth Factor (HGF) in patients undergoing hemodialysis HD and the influence of different HD modalities on their levels. Methods. We performed a prospective crossover study in which HD patients were randomized to undergo 3-month treatment periods with bicarbonate hemodialysis (BHD) followed by online hemodiafiltration (HDF). Clinical data, laboratory parameters, and myostatin and HGF serum levels were collected and compared. Results. Ten patients and six controls (C) were evaluated. In any experimental condition myostatin and HGF levels were higher in HD than in C. At enrollment and after BHD there were not significant correlations, whereas at the end of the HDF treatment period myostatin and HGF were inversely correlated (r −0.65, p < 0.05), myostatin serum levels inversely correlated with transferrin (r −0.73, p < 0.05), and HGF levels that resulted positively correlated with BMI (r 0.67, p < 0.05). Moving from BHD to HDF, clinical and laboratory parameters were unchanged, as well as serum HGF, whereas myostatin levels significantly decreased (6.3 ± 4.1 versus 4.3 ± 3.1 ng/ml, p < 0.05). Conclusions. Modulation of myostatin levels and myostatin/HGF balance by the use of different HD modalities might represent a novel approach to the prevention and treatment of HD-related muscle wasting syndrome.

Skeletal Muscle Regeneration and Oxidative Stress Are Altered in Chronic Kidney Disease.

Skeletal muscle atrophy and impaired muscle function are associated with lower health-related quality of life, and greater disability and mortality risk in those with chronic kidney disease (CKD). However, the pathogenesis of skeletal dysfunction in CKD is unknown. We used a slow progressing, naturally occurring, CKD rat model (Cy/+ rat) with hormonal abnormalities consistent with clinical presentations of CKD to study skeletal muscle signaling. The CKD rats demonstrated augmented skeletal muscle regeneration with higher activation and differentiation signals in muscle cells (i.e. lower Pax-7; higher MyoD and myogenin RNA expression). However, there was also higher expression of proteolytic markers (Atrogin-1 and MuRF-1) in CKD muscle relative to normal. CKD animals had higher indices of oxidative stress compared to normal, evident by elevated plasma levels of an oxidative stress marker, 8-hydroxy-2' -deoxyguanosine (8-OHdG), increased muscle expression of succinate dehydrogenase (SDH) and Nox4 and altered mitochondria morphology. Furthermore, we show significantly higher serum levels of myostatin and expression of myostatin in skeletal muscle of CKD animals compared to normal. Taken together, these data show aberrant regeneration and proteolytic signaling that is associated with oxidative stress and high levels of myostatin in the setting of CKD. These changes likely play a role in the compromised skeletal muscle function that exists in CKD.

Myostatin and carbohydrate disturbances

ABSTRACTPurpose/aim of the study: Myostatin is a myokine that has been shown to inhibit muscle growth and to have potentially deleterious effects on metabolism. The aim of the current study was to compare its circulating serum levels in subjects from the whole spectrum of carbohydrate disturbances leading to diabetes. Materials and methods: A total of 159 age-, sex-, and BMI-matched subjects participated in the study – 50 had normal glucose tolerance (NGT), 60 had prediabetes (PreDM), and 49 had type 2 diabetes mellitus (T2D). Oral glucose tolerance testing was used to determine glucose tolerance. Serum myostatin was quantified by means of ELISA. Results: Circulating serum myostatin levels were highest in patients with T2D, lower in subjects with prediabetes, and lowest in subjects with normoglycemia (all p < 0.05). Myostatin was shown to be positively associated with fasting plasma glucose, HOMA-IR, hepatic enzymes, uric acid, and FINDRISC questionnaire scores in both sexes. ROC analyses determined circulating myostatin levels to be of value for differentiating subjects with T2D (AUC = 0.72, p = 0.002 in men; AUC = 0.70, p = 0.004 in women) in the study population. After adjustment for potential confounders, in a multiple binary logistic regression model, serum myostatin added further information to traditional risk estimates in distinguishing subjects with T2D. Conclusions: Serum myostatin levels are higher with deterioration of carbohydrate tolerance. Furthermore, circulating myostatin is positively associated with traditional biochemical estimates of poor metabolic health. These data add to evidence of the involvement of this myokine in the pathogenesis of T2D.

Serum myostatin levels are independently associated with skeletal muscle wasting in patients with heart failure

BackgroundIt has been reported that skeletal muscle mass and strength are decreased in patients with heart failure (HF), and HF is associated with both reduced exercise capacity and adverse clinical outcomes. Myostatin has been known as a negative regulator of muscle growth, follistatin as the myostatin antagonist, maintaining tissue homeostasis. We thus determined serum myostatin levels in HF patients and whether they are associated with skeletal muscle wasting. Methods and resultsForty one consecutive HF patients (58±15years old, New York Heart Association class I–III) and 30 age-matched healthy subjects as controls (53±8years old) were studied. Serum myostatin levels were significantly lower in HF patients than controls (18.7±7.4 vs. 23.6±5.2ng/mL, P<0.001). Circumference of the thickest part of the right thigh was significantly small (468±72 vs. 559±37mm, P=0.001) and lower extremity muscular strength was lower in patients with HF (129±55 vs. 219±52N×m, P<0.001). Fourteen HF patients (34%) had muscle wasting. By univariate analysis, higher age, higher serum follistatin, and lower serum myostatin were significantly associated with the presence of muscle wasting. By multivariate analysis, serum myostatin levels were independently associated with muscle wasting (OR=0.77, 95% CI [0.58, 0.93], P=0.02). ConclusionSerum myostatin levels were significantly decreased in HF patients and associated with lower extremity muscle wasting, suggesting that myostatin may be an important factor for maintaining skeletal muscle mass and strength in HF.

Serum Myokines Levels in Patients with Endogenous Cushing Syndrome and Acromegaly: Cross-Sectional Case−Control Study

Myokines are produced and released by muscle cells in response to muscular contractions. Endogenous Cushing syndrome (CS) and acromegaly cause significant changes in muscle tissue leading to atrophy or hypertrophy. However, there is no data whether these endocrine abnormalities influence myokine secretion. To evaluate serum levels of myostatin, interleukin-6 (IL6) and irisin in patients with CS and acromegaly. Fasting serum samples were taken and stored in aliquot at ≤-20°C from consecutive subjects with clinically evident and biochemically confirmed active CS, acromegaly and healthy volunteers matched by age, sex and body mass index (BMI). Commercially available kits were used to assay serum myokine levels. Grip strength was measured by a dynamometer. Insulin-like growth factor-1 (IGF1) was measured by immunochemiluminescence assay (Liaison), twenty-four hours urine free cortisol (24hUFC) ― by immunochemiluminescence assay (Vitros ECi), salivary free cortisol ― by electrochemiluminescence assay (Cobas). One-way ANOVA was utilized to assess the difference between groups. We enrolled 88 subjects: 30 patients suffered from CS (group 1), 28 ― acromegaly (2) and 30 matched healthy controls (3) with no difference among the groups in sex, age and BMI (p=0.492, 0.062 and 0.174 respectively). Mean 24hUFC in subjects with CS and mean IGF1 in subjects with acromegaly were significantly higher as compared to other groups (p<0.001). Right-hand grip strength was lower in patients with CS as compared to both patients with acromegaly and healthy subjects (p=0.04). However, among these young adults we did not find statistically significant differences in measured myokines levels: irisin ― p=0.15; IL6 ― p=0.34; myostatin ― p=0.50. There was a significant correlation between myostatin and irisin in the whole group of people and in every separately analyzed subset of patients (p<0.001), but no correlation was found between any measured myokines and 24hUFC or IGF1. Hypercortisolism or supraphysiological IGF1 levels do not significantly influence serum levels of myostatin, IL6 and irisin in young adults.

Factors Associated with the Serum Myostatin Level in Patients Undergoing Peritoneal Dialysis: Potential Effects of Skeletal Muscle Mass and Vitamin D Receptor Activator Use.

Myostatin is a member of the transforming growth factor-β family, which regulates synthesis and degradation of skeletal muscle proteins and is associated with the development of sarcopenia. It is up-regulated in the skeletal muscle of chronic kidney disease patients and is considered to be involved in the development of uremic sarcopenia. However, serum myostatin levels have rarely been determined, and the relationship between serum myostatin levels with clinical and metabolic factors remains unknown. This cross-sectional study investigated the association between serum myostatin level and clinical factors in 69 outpatients undergoing peritoneal dialysis. Serum myostatin level was determined by commercially available enzyme-linked immunosorbent assay (ELISA). Univariable and multivariable analysis were conducted to determine factors associated with serum myostatin levels. The factors included age, sex, diabetes mellitus, dialysis history, body mass index, residual kidney function, peritoneal dialysate volume, serum biochemistries, and the use of vitamin D receptor activators (VDRAs). Mean serum myostatin level was 7.59±3.37ng/mL. There was no association between serum myostatin level and residual kidney function. Serum myostatin levels were significantly and positively associated with lean body mass measured by the creatinine kinetic method and negatively associated with the use of VDRAs after adjustment for potential confounding factors. Our study indicated that serum myostatin levels are associated with skeletal muscle mass and are lower in patients treated with VDRAs. Further studies are necessary to determine the significance of measuring serum myostatin level in patients undergoing peritoneal dialysis.

Skeletal muscle mass adjusted by height correlated better with muscular functions than that adjusted by body weight in defining sarcopenia.

Sarcopenia, characterized by low muscle mass and function, results in frailty, comorbidities and mortality. However, its prevalence varies according to the different criteria used in its diagnosis. This cross-sectional study investigated the difference in the number of sarcopenia cases recorded by two different measurement methods of low muscle mass to determine which measurement was better. We recruited 878 (54.2% female) individuals aged over 65 years and obtained their body composition and functional parameters. Low muscle mass was defined as two standard deviations below either the mean height-adjusted (hSMI) or weight-adjusted (wSMI) muscle mass of a young reference group. The prevalence of sarcopenia was 6.7% vs. 0.4% (male/female) by hSMI, and 4.0% vs. 10.7% (male/female) by wSMI. The κ coefficients for these two criteria were 0.39 vs. 0.03 (male/female), and 0.17 in all subjects. Serum myostatin levels correlated positively with gait speed (r = 0.142, p = 0.007) after adjustment for gender. hSMI correlated with grip strength, cardiopulmonary endurance, leg endurance, gait speed, and flexibility. wSMI correlated with grip strength, leg endurance, gait speed, and flexibility. Since hSMI correlated more closely with grip strength and more muscular functions, we recommend hSMI in the diagnosis of low muscle mass.

Relationship between myostatin and irisin in type 2 diabetes mellitus: a compensatory mechanism to an unfavourable metabolic state?

Myostatin and irisin are two myokines related to energy metabolism, acting on skeletal muscle and recently suggested on adipose tissue in mice. However, the exact role of these myokines in humans has not been fully established. Our aim was to evaluate the relationship between serum levels of myostatin and irisin in type 2 diabetes mellitus patients and non-diabetic controls and to explore its links with metabolic parameters. Case-control study including 73 type 2 diabetes mellitus patients and 55 non-diabetic subjects as control group. Circulating myostatin and irisin levels were measured by enzyme-linked immunosorbent assays. Type 2 diabetes mellitus patients showed significantly lower myostatin levels (p = 0.001) and higher irisin levels (p = 0.036) than controls. An inverse relationship was observed between myostatin and irisin levels (p = 0.002). Moreover, in type 2 diabetes mellitus patients, after adjusting by confounder factors, myostatin was negatively related to fasting plasma glucose (p = 0.005) and to triglyceride levels (p = 0.028) while irisin showed a positive association with these variables (p = 0.017 and p = 0.006 respectively). A linear regression analysis showed that irisin and fasting plasma glucose levels were independently associated to myostatin levels and that myostatin and triglyceride levels were independently associated to irisin concentrations in type 2 diabetes mellitus patients. Our results suggest that serum levels of myostatin and irisin are related in patients with type 2 diabetes. Triglyceride and glucose levels could modulate myostatin and irisin concentrations as a compensatory mechanism to improve the metabolic state in these patients although further studies are needed to elucidate whether the action of these myokines represents an adaptative response.