Follistatin Levels Research Articles

The effect of TRX, combined with vibration training, on BMI, the body fat percentage, myostatin and follistatin, the strength endurance and layup shot skills of female basketball players

IntroductionTrx Vibration Training (TVT) focuses on using the entire body weight in combination with vibration. While research has separately examined TRX training and vibration training, there is limited literature on the combined effects of these two methods specifically for female individuals. Therefore, the objective of this study was to examine the impact of combining TRX and vibration training (TVT) on various factors including body mass index (BMI), body fat percentage (BFP), myostatin (MSTN), follistatin (FLST), endurance, and Lay up shooting skills of female basketball players. By addressing this research gap, we aim to shed light on the potential benefits of incorporating TRX and vibration exercises into the training regimen of female basketball players. MethodThe study sample comprised 24 female players who were divided into two groups of equal size, with each group consisting of 12 female players: the experimental group (n = 12, age = 19.17 ± 0.68 years, height = 168.33 ± 0.89 cm, weight = 67.00 ± 2.17 kg, training age = 4.54 ± 0.45 years) and the control group (n = 12, age = 19.33 ± 0.78 years, height = 168.08 ± 2.02 cm, weight = 67.33 ± 1.50 kg, training age = 4.58 ± 0.52 years). The experimental method was employed in the study. For eight weeks, the program was used (TVT), with the experimental group participants completing three training sessions each week. The TVT training lasted between 30 and 45 min, out of the overall training session time, which ranged from 90 to 120 min. The control group used a conventional program without Trx Vibration training. Study variables were evaluated before and after the intervention, and a two-way ANOVA was used for repeated measures. ResultsThe results of the study showed the superiority of the experimental group over the control group in BMI (p = 0.037, [d] = 0.64), BFP (p = 0.001, [d] = 2.97), FLST levels (p = 0.029, [d] = 0.68), MSTN (p = 0.001, [d] = 2.04), endurance (CMS) (p = 0.001, [d] = 4.56), and Lay up skill Y (s) (p = 0.001, [d] = 4.27), Y (sc) (p = 0.012, [d] = 4.27). ConclusionThe results showed that, when comparing the two groups, the TVT program significantly improved the study's variables. Basketball players' motor abilities and skill performance improved after eight weeks of training, and coaches are advised to take this into account when developing seasonal training plans.

Elevated circulating follistatin associates with increased risk of mortality and cardiometabolic disorders

Background and aimsPrevious study showed that elevated circulating hepatokine follistatin (FST) associates with an increased risk of type 2 diabetes by inducing adipose tissue insulin resistance. Here we explore further the relationships between plasma FST levels with mortality and health outcomes. Methods and resultsThe population-based Malmö Diet Cancer cardiovascular cohort (n = 4733, age 45–68 years) was used to study plasma FST in relation to incidence of health outcomes, by linkage with national patient registers. Cox regression analysis was used to assess the associations of plasma FST and outcomes, with adjustments for multiple potential confounding factors. During the mean follow-up time of 22.64 ± 5.84 years in 4,733 individuals, 526 had incident stroke, 432 had ischemic stroke, 530 had incident coronary events (CE), 339 had incident heart failure (HF), 320 had incident chronic kidney disease (CKD) and 1,843 individuals died. Hazard ratio (HR) per standard deviation increase in FST levels adjusted for multiple risk factors was 1.05 (95%CI: 1.00–1.11, p = 0.036) for mortality; 1.10 (95%CI: 1.00–1.20, p = 0.042) for stroke; 1.13 (95%CI: 1.03–1.25, p = 0.014) for ischemic stroke; 1.16 (95%CI: 1.03–1.30, p = 0.015) for HF; and 1.38 (95%CI: 1.12–1.70, p = 0.003) for a diagnosis of CKD. In MDC-CC individuals without prevalent or incident diabetes, the association between FST and stroke, CE and CKD remained significant; but not with mortality or HF. ConclusionsElevated circulating FST associates with an increased risk of mortality and HF, which partly may be mediated by diabetes. FST also associated with stroke, ischemic stroke, CE and CKD, independently of established risk factors including diabetes.

Serum Follistatin Levels are Independently Associated with Exercise Tolerance in Patients with Obesity

ABSTRACT Objective Follistatin (FST)/myostatin (MST) myokine-signaling axis is important for muscle metabolism and pathogenesis of obesity. FST, mainly secreted by skeletal muscle and liver, inhibits MST and affects skeletal muscle synthesis. This study aimed to identify the characteristics of myokines and independent predictors of serum FST levels in patients with obesity. Methods In this retrospective cross-sectional study, 226 patients (mean age, 46.6 years; men, 35.4%) with obesity who initially visited an outpatient clinic between June 2014 and September 2020, were included and classified into obesity (25.0 ≤ body mass index (BMI) < 35.0 kg/m2) and severe obesity (BMI ≥35 kg/m2) groups based on the guidelines of the Japan Society for the Study of Obesity. Body composition was measured using bioelectrical impedance analysis and computed tomography. Muscle strength, exercise tolerance, metabolic parameters, and myokines were measured, including serum levels of FST, MST, irisin, and brain-derived neurotrophic factor. Results Serum FST levels were significantly higher in the severe obesity group than in the obesity group (median: 768.4 vs. 895.1 pg/mL, P = 0.020). However, the levels of other myokines showed no significant differences between the groups. In Model 1, which included factors that significantly correlated with FST levels, stepwise multivariate regression analysis revealed peak oxygen uptake (VO2) as an independent predictor of FST levels based on the significance of the univariate analysis. Additionally, Model 2 was analyzed by adding myokine level to Model 1, revealing that peak VO2, MST, and irisin levels were independent predictors of FST levels. Conclusion Serum FST levels were higher in patients in the severe obesity group compared to those in the obesity group. There was an independent association between low exercise tolerance and elevated serum FST levels.

Circulating Growth Differentiation Factors 11 and 8, Their Antagonists Follistatin and Follistatin-Like-3, and Risk of Heart Failure in Elders.

Heterochronic parabiosis has identified growth differentiation factor (GDF)-11 as a potential means of cardiac rejuvenation, but findings have been inconsistent. A major barrier has been lack of assay specificity for GDF-11 and its homolog GDF-8. We tested the hypothesis that GDF-11 and GDF-8, and their major antagonists follistatin and follistatin-like (FSTL)-3, are associated with incident heart failure (HF) and its subtypes in elders. Based on validation experiments, we used liquid chromatography-tandem mass spectrometry to measure total serum GDF-11 and GDF-8, along with follistatin and FSTL-3 by immunoassay, in 2 longitudinal cohorts of older adults. In 2 599 participants (age 75.2 ± 4.3) followed for 10.8 ± 5.6 years, 721 HF events occurred. After adjustment, neither GDF-11 (HR per doubling: 0.93 [0.67, 1.30]) nor GDF-8 (HR: 1.02 per doubling [0.83, 1.27]) was associated with incident HF or its subtypes. Positive associations with HF were detected for follistatin (HR: 1.15 [1.00, 1.32]) and FLST-3 (HR: 1.38 [1.03, 1.85]), and with HF with preserved ejection fraction for FSTL-3 (HR: 1.77 [1.03, 3.02]). (All HRs per doubling of biomarker.) FSTL-3 associations with HF appeared stronger at higher follistatin levels and vice versa, and also for men, Blacks, and lower kidney function. Among older adults, serum follistatin and FSTL-3, but not GDF-11 or GDF-8, were associated with incident HF. These findings do not support the concept that low serum levels of total GDF-11 or GDF-8 contribute to HF late in life, but do implicate transforming growth factor-β superfamily pathways as potential therapeutic targets.

Investigation of cardiovascular risk parameters in adolescents with metabolic syndrome.

Metabolic syndrome leading to type 2 diabetes mellitus and cardiovascular diseases is a chronic multifactorial syndrome, associated with low-grade inflammation status. In our study, we aimed at assessing the serum levels of follistatin (FST), pregnancy-associated plasma protein-A (PAPP-A), and platelet/endothelial cell adhesion molecule-1 (PECAM-1) in adolescent patients with metabolic syndrome. This study was performed in 43 (19 males, 24 females) metabolic syndrome adolescents and 37 lean controls matched for age and sex. The serum levels of FST, PECAM-1, and PAPP-A were measured by using ELISA method. Serum FST and PAPP-A levels in metabolic syndrome were significantly higher than those of controls (p < 0.005 and p < 0.05). However, there was no difference in serum PECAM-1 levels between metabolic syndrome and control groups (p = 0.927). There was a significant positive correlation between serum FST and triglyceride (r = 0.252; p < 0.05), and PAPP-A and weight, (r = 0.252; p < 0.05) in metabolic syndrome groups. Follistatin was determined statistically significant in both univariate (p = 0,008) and multivariate (p = 0,011) logistic regression analysis. Our findings indicated a significant relationship between FST and PAPP-A levels and metabolic syndrome. These findings offer the possibility of using these markers in diagnosis of metabolic syndrome in adolescents as the prevention of the future complications.

LncRNA NEAT1 and MALAT1 are involved in polycystic ovary syndrome pathogenesis by functioning as competing endogenous RNAs to control the expression of PCOS-related target genes.

Accumulating evidence has shown an abnormal expression of several non-coding RNAs in ovarian tissues which might be closely linked with the pathogenesis of PCOS. The aim of this study was to identify competing endogenous (ce) RNA network: long non-coding RNA (lncRNA), microRNA (miRNA) and their target genes: androgen receptor (AR), follistatin (FST) and insulin receptor substrate-2 (IRS-2), which are relevant to PCOS, to underline the molecular pathogenesis of PCOS and assist in early diagnosis and treatment. Bioinformatic analysis was performed to retrieve a ceRNA network: [lncRNA (NEAT1 and MALAT1) - miRNA (miR-30a-5p and miR-30d-5p) - mRNA (AR, FST and IRS-2)] linked to PCOS. Expression of the selected RNAs was examined by qPCR in peripheral blood leukocytes obtained from 73 PCOS patients (41 obese and 32 non-obese) and 31 healthy controls. PCOS patients showed significantly higher expression levels of NEAT1, miR-30a-5p, AR, FST and IRS-2, with significantly lower expression levels of MALAT1 and miR-30d-5p relative to controls especially in obese versus non-obese patients. Receiver operating characteristic (ROC) curve analysis indicated that most of the selected RNAs could serve as potential early diagnostic markers for PCOS with the highest efficiency obtained upon combining NEAT1 and miR-30d-5p or MALAT1 and miR-30a-5p with either of PCOS target genes. Moreover, all addressed RNAs had been proved as potential predictors of PCOS. The obtained data of ceRNA network raised the possibility that NEAT1 overexpression may increase the expression levels of AR, FST and IRS-2 by sponging miR-30d-5p, while low expression of MALAT1 may allow higher expression of the above genes via increasing miR-30a-5p, suggesting their involvement in PCOS pathogenesis and promising role for future diagnosis and targeted therapy.

Maternal Serum Activin A, Inhibin A and Follistatin-Related Proteins across Preeclampsia: Insights into Their Role in Pathogenesis and Prediction.

Within the endocrine-paracrine signalling network at the maternal-foetal interface, the activin-inhibin-follistatin system modulates extravillous trophoblast invasion, suggesting a potential role in preeclampsia pathogenesis. This study aimed to compile the evidence published in the last decade regarding the variation in maternal serum activins, inhibin- and follistatin-related proteins in preeclamptic pregnancies compared to healthy pregnancies, and to discuss their role in predicting and understanding the pathophysiology of preeclampsia. A scoping review was conducted in MEDLINE, EMBASE and LILACS databases to identify studies published within the last ten years (2012-2022). Thirty studies were included. None of the studies addressed maternal serum changes of isoforms different from activin A, inhibin A, follistatin, and follistatin-like 3. Sixteen studies evaluated the potential of these isoforms in predicting preeclampsia through the area under the curve from a receiver operating characteristic curve. In preeclampsia, inhibin A is upregulated in all trimesters, whereas activin A increases exclusively in the late second and third trimesters. Serum follistatin levels are reduced in women with preeclampsia during the late second and third trimesters. However, changes in follistatin-like 3 remain inconclusive. Inhibin A and activin A can potentially serve as biomarkers of early-onset preeclampsia based on the outcomes of the receiver operating characteristic curve analysis. Further investigations are encouraged to explore the feasibility of quantifying maternal serum levels of activin A and inhibin A as a clinical tool in early preeclampsia prediction.

Association of activins, follistatins and inhibins with incident hip fracture in women with postmenopausal osteoporosis: a proof of concept, case-control study.

The activins-follistatins-inhibins (AFI) hormonal system is considered to regulate muscle and bone mass. We aimed to evaluate AFI in postmenopausal women with an incident hip fracture. In this post-hoc analysis of a hospital based case-control study, we evaluated circulating levels of the AFI system in postmenopausal women with a low-energy hip fracture admitted for fixation compared with postmenopausal women with osteoarthritis scheduled for arthroplasty. Circulating levels of follistatin (p = 0.008), FSTL3 (p = 0.013), activin B and AB (both p < 0.001), as well as activin AB/follistatin and activin AB/FSTL3 ratios (p = 0.008 and p = 0.029, respectively) were higher in patients than controls in unadjusted models. Differences for activins B and AB remained after adjustment for age and BMI (p = 0.006 and p = 0.009, respectively) and for FRAX-based risk for hip fracture (p = 0.008 and p = 0.012, respectively) but were lost when 25OHD was added to the regression models. Our data indicate no major changes in the AFI system in postmenopausal women at the time of hip fracture compared to postmenopausal women with osteoarthritis except for higher activin B and AB levels, whose significance, however, was lost when 25OHD was added to the adjustment models. Clinical Trials identifier: NCT04206618.

Correlation between Resistin and Follistatin hormones with pregnancy outcome in samples of Iraqi women undergoing ICSI cycle

Resistin and follistatin levels have been found to be high in polycystic ovarian syndrome (PCOS) patients, that play role in pathophysiology of PCOS and pregnancy status of women having ICSI cycle. This study aimed to determine the relationship between the hormone levels and pregnancy outcome in PCOS and non-PCOS women undergoing intracytoplasmic sperm injection (ICSI) program. The study was done at Higher Institute for Infertility Diagnosis and Assisted Reproductive Technologies from 2022 to 2023. Eighty infertile women participating in the IVF/ICSI treatment. They were split to control (40 non-polycystic ovarian syndrome- PCOS women) and 40 women for PCOS group. They were subdividing to subgroups’ according to body max index (BMI; normal and overweight / obese). ELISA method was used to measure hormone level at day 2 and follicular fluid and serum at day of ova pick up. About 38.8% of study participants were got pregnant. Means of serum resistin and follistatin in day 2 and OPU were significantly higher in patients with PCOS and normal BMI level while follistatin at day 2 and in follicular fluid (FF) were significantly higher in participants who got pregnant. Follistatin level at day 2 &gt; 9.89 ng/ml and in FF &gt; 15.06 ng/ml and might be as a predictor for occurrence of pregnancy after ICSI. The cutoff point of follistatin level in the serum at day two and in FF at the day OPU was found to be a predictor of pregnancy following ICSI, while no correlation was found between resistin and pregnancy outcome.

Umbilical cord mesenchymal stem cell-derived exosomal Follistatin inhibits fibrosis and promotes muscle regeneration in mice by influencing Smad2 and AKT signaling

IntroductionPromoting muscle regeneration through stem cell therapy has potential risks. We investigated the effect of umbilical cord mesenchymal stem cells (UMSCs) Exosomes (Exo) Follistatin on muscle regeneration.Material and methodsThe Exo was derived from UMSCs cells and was utilized to affect the mice muscle injury model and C2C12 cells myotubes atrophy model. The western blot, qRT-PCR and IF were utilized to determine the effects of Exo on the levels of Follistatin, MyHC, MyoD, Myostatin, MuRF1, MAFbx, α-SMA, Collagen I, Smad2, and AKT. In addition, HE and Masson staining were used to assess muscle tissue damage in mice.ResultsThe level of Follistatin in Exo was significantly higher than that in UMSCs. UMSCs-Exo increased the levels of Follistatin, MyHC, MyoD, and p-Smad2 and decreased the levels of Myostatin, MuRF1, MAFbx, α-SMA, Collagen I, p-AKT, and p-mTOR in mice or C2C12 cells. In addition, UMSCs-Exo decreased levels of inflammation and fibrosis in mice. However, UMSCs-Exo-si-Follistatin reversed the effect of UMSCs-Exo. Transfection of oe-Smad2 up-regulated the protein levels of Collagen I, α-SMA, and changed the ratio of p-Smad2/Smad2 expression to 0.33, and 0.34, 0.73. LY294002 decreased the levels of MyHC, MyoD, and the ratio of p-AKT/ AKT and p-mTOR/mTOR expression to 0.12, 0.17, 0.33, and 0.41, increased the levels of MuRF1 and MAFbx to 0.36 and 0.34.ConclusionsThis study demonstrated that Follistatin in UMSCs-Exo inhibits fibrosis and promotes muscle regeneration in mice by regulating Smad and AKT signaling.

Effects of Growth Hormone on Muscle and Bone in Female Mice: Role of Follistatin.

The interactions between muscle and bone are noted in the clinical relationships between sarcopenia and osteoporosis. Myokines secreted from the skeletal muscles play roles in muscle-bone interactions related to various physiological and pathophysiological states. Although numerous evidence suggests that growth hormone (GH) influences both muscle and bone, the effects of GH on the muscle-bone interactions have remained unknown. We, therefore, investigated the influences of GH administration for 8 weeks on muscle and bone, including myokine expression, in mice with or without ovariectomy (OVX). GH administration significantly increased muscle mass in the whole body and lower limbs, as well as tissue weights of the extensor digitorum longus (EDL) and soleus muscles in mice with or without OVX. Moreover, it markedly increased grip strength in both mice. As for femurs, GH administration significantly increased cortical thickness and area in mice with or without OVX. Moreover, GH significantly blunted the decrease in the ratio of bone volume to tissue volume at the trabecular bone in mice with OVX. GH administration significantly decreased follistatin mRNA levels in the EDL, but not the soleus, muscles in mice with or without OVX, although it did not affect the other myokines examined. However, GH administration significantly elevated serum follistatin levels in mice. In conclusion, this study indicates that GH administration increases skeletal muscle mass and grip strength and cortical and trabecular bone-related parameters obtained by micro-computed tomography analyses in mice. However, myokine regulation might not be critical for the effects of GH on muscle and bone.

Tubule-Derived Follistatin Is Increased in the Urine of Rats with Renal Ischemia and Reflects the Severity of Acute Tubular Damage.

Activin A, a member of the TGF-beta superfamily, is a negative regulator of tubular regeneration after renal ischemia. Activin action is controlled by an endogenous antagonist, follistatin. However, the role of follistatin in the kidney is not fully understood. In the present study, we examined the expression and localization of follistatin in normal and ischemic rat kidneys and measured urinary follistatin in rats with renal ischemia to assess whether urinary follistatin could serve as a biomarker for acute kidney injury. Using vascular clamps, renal ischemia was induced for 45 min in 8-week-old male Wistar rats. In normal kidneys, follistatin was localized in distal tubules of the cortex. In contrast, in ischemic kidneys, follistatin was localized in distal tubules of both the cortex and outer medulla. Follistatin mRNA was mainly present in the descending limb of Henle of the outer medulla in normal kidneys but was upregulated in the descending limb of Henle of both the outer and inner medulla after renal ischemia. Urinary follistatin, which was undetectable in normal rats, was significantly increased in ischemic rats and peaked 24 h after reperfusion. There was no correlation between urinary follistatin and serum follistatin. Urinary follistatin levels were increased according to ischemic duration and were significantly correlated with the follistatin-positive area as well as the acute tubular damage area. These results suggest that follistatin normally produced by renal tubules increases and becomes detectable in urine after renal ischemia. Urinary follistatin might be useful to assess the severity of acute tubular damage.

Quiescent ovarian cancer cells secrete follistatin to induce chemotherapy resistance in surrounding cells in response to chemotherapy.

We recently reported that the transcription factor NFATC4, in response to chemotherapy, drives cellular quiescence to increase OvCa chemoresistance. The goal of this work was to better understand the mechanisms of NFATC4 driven OvCa chemoresistance. We used RNA-seq to identify NFATC4 mediated differential gene expression. CRISPR-Cas9 and FST neutralizing antibody were used to assess impact of loss of FST function on cell proliferation and chemoresistance. ELISA was used to quantify FST induction in patient samples and in vitro in response to chemotherapy. We found that NFATC4 upregulates follistatin (FST) mRNA and protein expression predominantly in quiescent cells and FST is further upregulated following chemotherapy treatment. FST acts in at least a paracrine manner to induce a p-ATF2 dependent quiescent phenotype and chemoresistance in non-quiescent cells. Consistent with this, CRISPR KO of FST in OvCa cells or antibody mediated neutralization of FST sensitizes OvCa cells to chemotherapy treatment. Similarly, CRISPR KO of FST in tumors increased chemotherapy-mediated tumor eradication in an otherwise chemotherapy resistant tumor model. Suggesting a role for FST in chemoresistance in patients, FST protein in the abdominal fluid of OvCa patients significantly increases within 24 hours of chemotherapy exposure. FST levels decline to baseline levels in patients no longer receiving chemotherapy with no evidence of disease. Furthermore, elevated FST expression in patient tumors is correlated with poor progression free, post-progression free, and overall survival. FST is a novel therapeutic target to improve OvCa response to chemotherapy and potentially reduce recurrence rates.

Evaluation of Associations of Growth Differentiation Factor-11, Growth Differentiation Factor-8, and Their Binding Proteins Follistatin and Follistatin-Like Protein-3 With Dementia and Cognition.

Studies using heterochronic parabiosis discovered that circulating factors mediate brain aging in animal models. We assessed growth differentiation factors (GDF)-11 and GDF-8 using mass spectrometry and inhibitors follistatin and follistatin-like protein-3 (FSTL-3) with ELISA in the Cardiovascular Health Study (CHS; N = 1 506) and the Health, Aging and Body Composition (Health ABC) Study (N = 1 237). CLL-11 and beta-2 microglobulin (β2M) were measured with ELISA in a subset of 400 individuals in Health ABC. Associations were assessed with cognitive function, brain magnetic resonance imaging (MRI) findings (CHS only), and incident dementia using correlations, linear regression, and Cox proportional hazards models. In CHS, levels of GDF-11, GDF-8, and follistatin were not correlated cross-sectionally with the 3MSE or DSST, brain MRI findings of white matter hyperintensity, atrophy, or small infarcts, nor were they associated with incident dementia. FSTL-3 was modestly correlated with poorer cognitive function, greater white matter hyperintensities, and atrophy on MRI, as well as with incident dementia with an adjusted hazard ratio (HR) of 1.72 (95% CI = 1.13, 2.61) per doubling of FSTL-3. FSTL-3 was not associated with cognition or dementia in Health ABC, but GDF-8 was associated with both. The adjusted HR for incident dementia was 1.50 (95% CI = 1.07, 2.10) per doubling of GDF-8. Total GDF-11 level was not related to cognition or dementia in older adults. Associations of GDF-8 with cognitive outcomes in Health ABC were not expected, but consistent with animal models. Associations of FSTL-3 with cognition, brain abnormalities, and incident dementia in CHS implicate TGFβ superfamily inhibition in the pathogenesis of dementia.

The relationship between follistatin and sarcopenia in elderly

Introduction: Sarcopenia is a multifactorial condition characterized by progressive and comprehensive mass loss accompanied by skeletal muscle strength or function. It can be triggered by physical inactivity, hormonal changes, energy, protein intake, oxidative stress and inflammatory processes. The state of inactivity underlying sarcopenia is related to follistatin levels. Methods: an analytical cross-sectional study conducted in Posyandu or Elderly Associations in Denpasar City with subjects aged ≥60 years old started from January 2021 to September 2021. The data collected were anthropometric measurements, muscle mass, grip strength, walking speed and serum follistatin levels. Sarcopenia was diagnosed based on the AWGS criteria. Bivariate analysis was performed using the Mann-Whitney analysis to determine the difference in the mean of the independent variables and the Spearman's test to determine the relationship between sarcopenia and follistatin levels. Results: 75 subjects were selected, and 15 (20%) subjects were diagnosed with sarcopenia. The results of the Spearman correlation test of upper arm circumference, waist circumference, calf circumference, SMI, walking speed, hand grip strength and follistatin levels only found a significant negative relationship between waist circumference and follistatin levels r= -0,309, p= 0,016. No differences in mean follistatin levels with sarcopenia and non-sarcopenia group p= 0,516. There was no significant relationship between follistatin levels and sarcopenia p= 0,615. Conclusion: There is no correlation between follistatin levels and sarcopenia in the elderly. However, follistatin is inversely correlated with waist circumference.

Effects of functional training with blood occlusion on the irisin, follistatin, and myostatin myokines in elderly men

BackgroundThis study aimed to determine the efficacy of functional training with and without blood flow restriction (BFR) on muscle hypertrophy indices and strength in older men.MethodsThirty older adults (67.7 ± 5.8 years) were randomly assigned to three groups: functional training (FT), functional training with BFR (FTBFR), and control (C). Participants in experimental groups were trained in three sessions per week for six weeks. They performed 11 whole body exercises, in 2–4 sets of 10 repetitions. FTBFR group wore pneumatic cuffs on their extremities that began with 50% of estimated arterial occlusion pressure which increased by 10% every two weeks. Blood samples were obtained, and static strength tests were evaluated at baseline and after the training program. A One-Way Analysis of Covariance was used to interpret the data.ResultsA significant increase in follistatin levels (p = 0.002) and reduction in myostatin levels (p = 0.001) were observed in FT and FTBFR groups; there was a considerable increase in the F:M ratio in both training groups (p = 0.001), whereas it decreased in C group. These changes were accompanied by significant improvements in handgrip (p = 0.001) and shoulder girdle (p = 0.001) strength in both experimental groups, especially in the FTBFR group. However, the levels of irisin were not statistically changed following interventions (p = 0.561).ConclusionThe findings showed that FT was effective in increasing circulating biomarkers involved in hypertrophy in older adults while adding BFR to FT had a slight increase in these biomarkers but had a tremendous increase in muscle strength.

Intensity Dependent Effects of Interval Resistance Training on Myokines and Cardiovascular Risk Factors in Males With Obesity.

ObjectiveTo determine the effects of different intensities of interval resistance training (IRT) protocols on the levels of select myokines (decorin, follistatin, myostatin, activin A, transforming growth factor beta-1 [TGF-β1]), and cardiometabolic and anthropometric measures in males with obesity.MethodsForty-four obese males (age: 27.5 ± 9.4 yr.; height: 165.4 ± 2.8 cm; weight: 97.9 ± 2.6 kg and BMI: 35.7 ± 4.3 kg/m2) were randomly assigned to one of four groups (n=11 per group): low-intensity interval resistance training (LIIRT), moderate-intensity interval resistance training (MIIRT), high-intensity interval resistance training (HIIRT) or control (C). The LIIRT group performed 10 exercises in 3 sets of 40% (20 repetitions), the MIIRT group performed 10 exercises in three sets of 60% (13 repetitions), and the HIIRT group performed 10 exercises in three sets of 80% (10 repetitions) of one maximum repetition (1RM), which were followed with active rest of 20% of 1RM and 15 repetitions. The resistance training groups exercised ~70 min per session, 3 days per week, for 12 weeks. Measurements were taken at baseline and after 12 weeks of exercise training.ResultsBaseline levels of myokines, cardiovascular risk factors, anthropometry, body composition, and cardio-respiratory fitness were not different between the four groups (p>0.05). The group x time interactions for decorin, activin A, follistatin, myostatin, and TGF-β1, total cholesterol (TC), triglyceride (TG), high-density cholesterol (HDL), low-density cholesterol (LDL), anthropometry, body composition, and cardio-respiratory fitness were statistically significant (p<0.05). There were increases in post-test values for decorin, follistatin, HDL (p<0.05) and decreases in TC, TG, TGF-β1, LDL, and myostatin levels in the LIIRT, MIIRT, and HIIRT groups compared to pretest values (p<0.05). Changes in fat mass, VO2peak, HDL, TG, glucose, activin A, decorin were not significant in LIIRT compared to the control group, while changes in activin A, follistatin, and TFG-β1 levels were greater in HIIRT and MIIRT groups compared to the LIIRT group (p<0.05).ConclusionThe LIIRT, MIIRT, and HIIRT protocols all produced beneficial changes in decorin, activin A, follistatin, myostatin, and TGF-β1 levels, and cardiometabolic risk factors, with greater effects from the MIIRT and HIIRT protocols compared to LIIRT.

Decreased myostatin in response to a controlled DASH diet is associated with improved body composition and cardiometabolic biomarkers in older adults: results from a controlled-feeding diet intervention study

BackgroundElevated concentrations of myostatin inhibit muscle growth, function and strength. Myostatin is a mediator of sarcopenia and is associated with insulin resistance. For this study we tested the response of a calorie-restricted Dietary Approaches to Stop Hypertension (DASH) diet on changes in myostatin, follistatin, and mystatin:follistatin ratio levels after 12 weeks in comparison to basline in adults aged 65 years and older. Furthermore we evaluated correlations between changes in myostatin, body composition and cardiometabolic biomarkers in this cohort of older adults.MethodsThis was a controlled-feeding diet intervention study in which females (n = 17) and males (n = 11) aged 65 years and older consumed either 85 g (n = 15) or 170 g (n = 13) of fresh lean beef within a standardized DASH diet for 12-weeks. Myostatin and follistatin concentrations were measured from fasted blood samples collected at 5 timepoints throughout the 12-week feeding intervention period. Correlations were assessed between changes in myostatin and follistatin levels and measures of body composition and cardiometabolic biomarkers.ResultsThere were no differences (p > 0.05) in circulating myostatin or follistatin levels between the beef intake groups. However, with beef groups combined myostatin decreased by 17.6% (p = 0.006) and the myostatin-to-follistatin ratio decreased by 16.5% (p < 0.001) in response to the study diet. Decreased myostatin was positively correlated with reductions in waist circumference (R2 = 0.163; p = 0.033) and fat mass (R2 = 0.233; p = 0.009). There was an inverse relationship between decreased myostatin and increased strength-to-weight ratio (R2 = 0.162; p = 0.034). The change in myostatin-to-follistatin ratio was associated with the change in skeletal muscle mass-to-fat mass ratio (R2 = 0.176; p = 0.026). Decreased myostatin was positively correlated with reductions in total cholesterol (R2 = 0.193; p = 0.012), LDL-C (R2 = 0.163; p = 0.031), insulin (R2 = 0.234; p = 0.009), and HOMA-IR (R2 = 0.248; P = 0.007). There was no change (p > 0.05) in circulating follistatin concentrations in response to the diet intervention.ConclusionsThe outcomes from this study suggest that a calorie-restricted DASH diet has the potential to reduce myostatin concentrations in older adults. Furthermore these outcomes support interrelationships between myostatin, body composition and cardiometabolic health in adults aged 65 years and older.Trial registrationClinicalTrials.gov; Identifier: NCT04127240; Registration Date: 15/10/ 2019.

Association of Pre-Transplant Angiopoietin-2 Index with the Risk of Acute Graft-Versus-Host Disease after Hematopoietic Stem Cell Transplantation

Objective:Angiogenic factors (AFs) released under endothelial stress are reflective of tissue healing, while some may also contribute to tissue damage/inflammation. We investigated whether alterations in the pre-transplant levels of AFs were associated with the risk of acute graft-versus-host disease (aGvHD).Materials and Methods:The pre-conditioning plasma levels of angiopoietin-2 (Ang2), endoglin, and follistatin were measured for 37 patients together with inflammatory markers. The index values defined were evaluated to better identify the alterations.Results:The patients had higher pre-conditioning levels of Ang2, endoglin, and follistatin compared to controls. The patients with aGvHD had higher Ang2 index and lower albumin index scores in comparison to those without aGvHD. Multivariate analysis revealed that the pre-transplant Ang2 index was an independent risk factor for aGvHD development.Conclusion:Pre-transplant evaluation of plasma Ang2 levels along with inflammatory status even before conditioning is associated with endothelial vulnerability. The pre-transplant Ang2 index could be a promising candidate to estimate the risk of aGvHD.

Serum follistatin level as a prognostic marker in Haploidentical stem cell transplantation

BackgroundThe treatment of hematological diseases with Haploidentical transplantation has made significant progress. Follistatin is an angiogenic factor that is elevated in the circulation after allogeneic Hematopoietic Cell Transplantation (HCT). Elevated follistatin levels have been linked to poor survival after graft versus host disease (GVHD). ObjectivePre- and post-transplant Follistatin levels were measured in patients subjected to Haploidentical HSCT and correlated with transplant outcomes. Patients and methodsThis study included 45 patients who underwent allogeneic stem cell transplants from Haploidentical donors. ResultsThe mean Follistatin level before stem cells infusion (88.81 ± 49.11 ng/ml) and at day 28 post-transplant (78.61 ± 45.50 ng/ml). The mean follistatin level was higher among the patients who had acute severe GVHD grade 3–4 pre-transplant at day zero and day 28 without statistical significance.The incidence of veno-occlusive disease was higher in patients with elevated serum follistatin levels on day 0 (108.58 ± 64.12 Vs 82.16 ± 46.05 ng/ml. p value = 0.134) and day 28 (112 ± 49.36 vs 66.06 ± 38.96 ng/ml) with statistically significance at day 28 post-transplant (p value = 0.011).After 180 days of follow-up, patients with high serum follistatin (i.e. >60 ng/ml) on day 28 post-transplant had lower OS, (P = 0.381). ConclusionIn the setting of Haploidentical HSCT, higher follistatin levels post-transplant are associated with severe acute GVHD and inferior overall survival.