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.

Chronic flavanol-rich cocoa powder supplementation reduces body fat mass in endurance athletes by modifying the follistatin/myostatin ratio and leptin levels.

Flavanols-rich cocoa has positive effects on lipid metabolism and might enhance the performance of athletes through an improvement in their body composition. To test this hypothesis a placebo-controlled intervention study in training endurance athletes who received 5 g of cocoa daily (425 mg of flavanols) for 10 weeks was performed. Dietary intake, body composition, exercise performance and plasma levels of follistatin, myostatin and leptin were measured. Cocoa intake significantly reduced body fat percentage (p = 0.020), specifically in the trunk (p = 0.022), visceral area (p = 0.034) and lower limbs (p = 0.004). The reduction in body fat mass was accompanied by an increase in plasma follistatin and a decrease in leptin, while myostatin levels remained unchanged. The intake of cocoa reduced the percentage of body fat of athletes, without any impact on athletes' performance. The change in fat body composition did not improve athletes' performance.

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.

Improvement in Skeletal Muscle Strength and Plasma Levels of Follistatin and Myostatin Induced by an 8-Week Resistance Training and Epicatechin Supplementation in Sarcopenic Older Adults.

To investigate the effects of resistance training and epicatechin supplementation on muscle strength, follistatin, and myostatin in older adults with sarcopenia, a total of 62 males with sarcopenia (68.63 ± 2.86 years) underwent a supervised 8-week randomized controlled trial. Participants were divided into resistance training (RT), epicatechin (EP), resistance training+epicatechin (RT+EP), and placebo (PL) in a double-blind method. A pretest and posttest measurement was conducted. One-way analysis of variance was used to analyze between-group differences. The significantly greatest increase was observed in follistatin, follistatin/myostatin ratio, leg press, and chest press in RT+EP comparing RT, EP, and PL groups, whereas myostatin decreased significantly only in RT+EP and RT groups. However, appendicular muscle mass index and timed up and go test were enhanced significantly in all experimental groups than the PL group (p ≤ .05). Consequently, by comparing the results between three experimental groups, the greatest improvement was detected in the RT+EP group. Therefore, using two interventions simultaneously seems to have a better impact on improving muscle growth factors and preventing the progression of sarcopenia.

A randomized-controlled trial pilot study examining the effect of extracorporeal magnetic innervation in the treatment of stress urinary incontinence in women.

INTRODUCTION: Peri- and postmenopausal women frequently suffer from urinary incontinence (UI). Generally, UI becomes more severe with age. It impacts physical, mental, and social functioning as well as the quality of life, often leading to depression. Extracorporeal magnetic innervation (ExMI) is a relatively new conservative treatment method for UI. OBJECTIVE: The aim of the study was to assess the effectiveness of ExMI in the treatment of stress UI in women. METHODS: A total of 52 women were included in the analysis: 28 participants were allocated to the experimental group (EG) and 24 to the control group (CG). The average age was 65.41 years (±SD 4.08). EG patients completed ExMI therapy. The treatment sessions lasted for 15 minutes, and occurred three times a week, for 4 weeks. No therapeutic intervention was applied to the CG. To objectify the treatment outcomes in both groups before and after the treatment, we measured myostatin concentration and performed the UI severity assessment (The Revised Urinary Incontinence Scale), perceived self-efficacy assessment (General Self-Efficacy Scale), and depression severity assessment (Beck Depression Inventory). RESULTS: The authors compared the EG results at the initial and final assessments and found a statistically significant improvement in severity of UI (P=0.001) and depression severity (P=0.006), and a decrease in myostatin concentration (P≤0.001). The authors did not find any statistically significant differences between all measured variables for the CG at the initial and final assessments. Furthermore, there were no statistically significant differences between all measured variables for the EG and the CG at the final assessment. CONCLUSION: Further trials are needed to determine optimal treatment protocols for various UI types and to evaluate long-term outcomes of the ExMI treatment.

The Effects of Fortetropin Supplementation on Body Composition, Strength, and Power in Humans and Mechanism of Action in a Rodent Model.

OBJECTIVE: The purpose of this study was to investigate the effects of Fortetropin on skeletal muscle growth and strength in resistance-trained individuals and to investigate the anabolic and catabolic signaling effects using human and rodent models. METHODS: In the rodent model, male Wistar rats (250 g) were gavage fed with either 1.2 ml of tap water control (CTL) or 0.26 g Fortetropin for 8 days. Then rats participated in a unilateral plantarflexion exercise bout. Nonexercised and exercised limbs were harvested at 180 minutes following and analyzed for gene and protein expression relative to mammalian target of rapamycin (mTOR) and ubiquitin signaling. For the human model, 45 (of whom 37 completed the study), resistance-trained college-aged males were divided equally into 3 groups receiving a placebo macronutrient matched control, 6.6 or 19.8 g of Fortetropin supplementation during 12 weeks of resistance training. Lean mass, muscle thickness, and lower and upper body strength were measured before and after 12 weeks of training. RESULTS: The human study results indicated a Group × Time effect (p ≤ 0.05) for lean mass in which the 6.6 g (+1.7 kg) and 19.8 g (+1.68 kg) but not placebo (+0.6 kg) groups increased lean mass. Similarly, there was a Group × Time effect for muscle thickness (p ≤ 0.05), which increased in the experimental groups only. All groups increased equally in bench press and leg press strength. In the rodent model, a main effect for exercise (p ≤ 0.05) in which the control plus exercise but not Fortetropin plus exercise increased both ubiquitin monomer protein expression and polyubiquitination. mTOR signaling was elevated to a greater extent in the Fortetropin exercising conditions as indicated by greater phosphorylation status of 4EBP1, rp6, and p70S6K for both exercising conditions. CONCLUSIONS: Fortetropin supplementation increases lean body mass (LBM) and decreases markers of protein breakdown while simultaneously increasing mTOR signaling.

Effects of Light-Emitting Diode Therapy on Muscle Hypertrophy, Gene Expression, Performance, Damage, and Delayed-Onset Muscle Soreness: Case-control Study with a Pair of Identical Twins.

OBJECTIVE: The aim of this study was to verify how a pair of monozygotic twins would respond to light-emitting diode therapy (LEDT) or placebo combined with a strength-training program during 12 weeks. DESIGN: This case-control study enrolled a pair of male monozygotic twins, allocated randomly to LEDT or placebo therapies. Light-emitting diode therapy or placebo was applied from a flexible light-emitting diode array (λ = 850 nm, total energy = 75 J, t = 15 seconds) to both quadriceps femoris muscles of each twin immediately after each strength training session (3 times/wk for 12 weeks) consisting of leg press and leg extension exercises with load of 80% and 50% of the 1-repetition maximum test, respectively. Muscle biopsies, magnetic resonance imaging, maximal load, and fatigue resistance tests were conducted before and after the training program to assess gene expression, muscle hypertrophy and performance, respectively. Creatine kinase levels in blood and visual analog scale assessed muscle damage and delayed-onset muscle soreness, respectively, during the training program. RESULTS: Compared with placebo, LEDT increased the maximal load in exercise and reduced fatigue, creatine kinase, and visual analog scale. Gene expression analyses showed decreases in markers of inflammation (interleukin 1ß) and muscle atrophy (myostatin) with LEDT. Protein synthesis (mammalian target of rapamycin) and oxidative stress defense (SOD2 [mitochondrial superoxide dismutase]) were up-regulated with LEDT, together with increases in thigh muscle hypertrophy. CONCLUSIONS: Light-emitting diode therapy can be useful to reduce muscle damage, pain, and atrophy, as well as to increase muscle mass, recovery, and athletic performance in rehabilitation programs and sports medicine.

Effects of elastic band resistance training and nutritional supplementation on muscle quality and circulating muscle growth and degradation factors of institutionalized elderly women: the Vienna Active Ageing Study (VAAS).

PURPOSE: Regular resistance exercise training and a balanced diet may counteract the age-related muscular decline on a molecular level. The aim of this study was to investigate the influence of elastic band resistance training and nutritional supplementation on circulating muscle growth and degradation factors, physical performance and muscle quality (MQ) of institutionalized elderly. METHODS: Within the Vienna Active Ageing Study, 91 women aged 83.6 (65.0-92.2) years were randomly assigned to one of the three intervention groups (RT, resistance training; RTS, resistance training plus nutritional supplementation; CT, cognitive training). Circulating levels of myostatin, activin A, follistatin, IGF-1 and GDF-15, as well as MQ and functional parameters were tested at baseline as well as after 3 and 6 months of intervention. RESULTS: MQ of lower extremities significantly increased in the RT group (+14 %) and RTS group (+12 %) after 6 months. Performance improved in the RT and RTS groups for chair stand test (RT: +18 %; RTS: +15 %). Follistatin increased only in the RT group (+18 %) in the latter phase of the intervention, accompanied by a decrease in the activin A-to-follistatin ratio (-7 %). IGF-1, myostatin and GDF-15 levels were not affected by the intervention. CONCLUSION: Our data confirm that strength training improves physical performance and MQ even in very old institutionalized women. This amelioration appears to be mediated by blocking muscle degradation pathways via follistatin rather than inducing muscle growth through the IGF-1 pathway. As plasma levels of biomarkers reflect an overall status of various organ systems, future studies of tissue levels are suggested.

Oral supplement enriched in HMB combined with pulmonary rehabilitation improves body composition and health related quality of life in patients with bronchiectasis (Prospective, Randomised Study).

BACKGROUND & AIMS: Pulmonary Rehabilitation (PR) is recommended for bronchiectasis but there is no data about its effect on body composition. The aim of this study is to assess the effect of Pulmonary Rehabilitation (PR) for 12 weeks in normally-nourished non-cystic-fibrosis bronchiectasis patients compared with the effect of PR plus a hyperproteic oral nutritional supplement enriched with beta-hydroxy-beta-methylbutyrate (HMB) on body composition, muscle strength, quality of life and serum biomarkers. METHODS: single center randomized controlled trial, parallel treatment design: Participants were randomly assigned to receive PR for 12 weeks or PR plus ONS (PRONS) (one can per day). Outcome assessments were performed at baseline, 12 weeks and 24 weeks: body composition (Dual-energy X-Ray Absorptiometry (DEXA), mid-arm muscle circumference (MAMC), phase angle by Bio-impedance), health related quality of life (Spanish QOL-B-V3.0, Physical Functioning Scale), handgrip strength, diet questionnaire, and plasma levels of prealbumin, myostatin and somatomedin-c. RESULTS: Thirty patients were randomized (15 per group) without differences in clinical and respiratory variables. In the PRONS group bone mineral density (BMD), mean and maximum handgrip dynamometry, MAMC, QOLB and prealbumin were significantly increased from baseline at 12 and 24 weeks and Fat free Mass (FFM) and FFM index, at 12 weeks. In the PR group only mean handgrip dynamometry and prealbumin were significantly increased at 12 and 24 weeks. In both groups plasma myostatin was reduced at 12 weeks (without significant differences). CONCLUSION: The addition of a hyperproteic ONS enriched with HMB to Pulmonary Rehabilitation could improve body composition, BMD, muscle strength and health related quality of life in bronchiectasis patients. Clinical Trials Number NCT02048397.

Protein supplementation increases postexercise plasma myostatin concentration after 8 weeks of resistance training in young physically active subjects.

Myostatin (MSTN) is a negative regulator of muscle growth even if some studies have shown a counterintuitive positive correlation between MSTN and muscle mass (MM). Our aim was to investigate the influence of 2 months of resistance training (RT) and diets with different protein contents on plasma MSTN, interleukin 1 beta (IL-1ß), interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α), and insulin-like growth factor 1 (IGF-1). Eighteen healthy volunteers were randomly divided in two groups: high protein (HP) and normal protein (NP) groups. Different protein diet contents were 1.8 and 0.85 g of protein·kg bw(-1)·day(-1) for HP and NP, respectively. Subjects underwent 8 weeks of standardized progressive RT. MSTN, IGF-1, IL-1ß, IL-6, and TNF-α were analyzed before and after the first and the last training sessions. Lean body mass, MM, upper-limb muscle area, and strength were measured. Plasma MSTN showed a significant increase (P<.001) after the last training in the HP group compared with NP group and with starting value. IGF-1 plasma concentration showed a positive correlation with MSTN in HP after the last training (r(2)=0.6456; P=.0295). No significant differences were found between NP and HP for IL-1ß, IL-6, TNF-α, and strength and MM or area. These findings suggest a "paradoxical" postexercise increase of plasma MSTN after 8 weeks of RT and HP diets. This MSTN elevation correlates positively with IGF-1 plasma level. This double increase of opposite (catabolic/anabolic) mediators could explain the substantial overlapping of MM increases in the two groups.

Chronic activity-based therapy does not improve body composition, insulin-like growth factor-I, adiponectin, or myostatin in persons with spinal cord injury.

UNLABELLED: Spinal cord injury (SCI) induces dramatic changes in body composition including reductions in fat-free mass (FFM) and increases in fat mass (FM). OBJECTIVE: To examine changes in body composition in response to chronic activity-based therapy (ABT) in persons with SCI. DESIGN: Longitudinal exercise intervention. METHODS: Seventeen men and women with SCI (mean age=36.1±11.5 years) completed 6 months of supervised ABT consisting of load bearing, resistance training, locomotor training, and functional electrical stimulation. At baseline and after 3 and 6 months of ABT, body weight, body fat, and FFM were assessed using dual-energy X-ray absorptiometry, and fasting blood samples were obtained to assess changes in insulin-like growth factor-I (IGF-I), adiponectin, and myostatin. RESULTS: Across all subjects, there was no change (P>0.05) in body weight, percent body fat, or FFM of the leg, arm, or trunk, whereas whole-body FFM declined (P=0.02, 50.4±8.4 to 49.2±7.4 kg). No changes (P=0.21-0.41) were demonstrated in IGF-I, adiponectin, or myostatin during the study. CONCLUSIONS: Chronic ABT focusing on the lower extremity does not slow muscle atrophy or alter body fat, body mass, or regional depots of FFM in persons with SCI. Further, it does not induce beneficial changes in adiponectin, myostatin, or IGF-I. Alternative exercise-based therapies are needed in SCI to reverse muscle atrophy and minimize the onset of related health risks.

Effects of oral creatine and resistance training on serum myostatin and GASP-1.

Myostatin is a catabolic regulator of skeletal muscle mass. The purpose of this study was to determine the effect of resistance training for 8 weeks in conjunction with creatine supplementation on muscle strength, lean body mass, and serum levels of myostatin and growth and differentiation factor-associated serum protein-1 (GASP-1). In a double-blinded design 27 healthy male subjects (23.42+/-2.2 years) were assigned to control (CON), resistance training+placebo (RT+PL) and resistance training+creatine supplementation (RT+CR) groups. The protocol consisted of 3 days per week of training for 8 weeks, each session including three sets of 8-10 repetitions at 60-70% of 1 RM for whole-body exercise. Blood sampling, muscular strength testing and body composition analysis (full body DEXA) were performed at 0, 4th and 8th weeks. Myostatin and GASP-1 was measured. Resistance training caused significant decrease in serum levels of myostatin and increase in that of GASP-1. Creatine supplementation in conjunction with resistance training lead to greater decreases in serum myostatin (p<0.05), but had not additional effect on GASP-1 (p>0.05). The effects of resistance training on serum levels of myostatin and GASP-1, may explain the increased muscle mass that is amplified by creatine supplementation.