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The adrenergic beta-2 agonists formoterol and salbutamol are used for the treatment of asthma and COPD but are also misused in sports competitions. Therefore, they are included in WADA regulations. Both drugs are mainly excreted in urine after administration via inhalation. A four-armed, double-blind cross-over clinical trial was conducted involving endurance-trained participants (12 females and 12 males). Inhalation dosages of 36 μg formoterol, 1200 μg salbutamol, a combination of both, or a placebo were administered before exercise. Serum and urine were collected after exercise and 3 and 24 h after administration. Here, we show the successful quantitation of formoterol, salbutamol, and its phase II metabolite salbutamol-4′-O-sulfate in all urine and serum samples using ultra-high performance liquid chromatography–tandem mass spectrometry. In the serum analysis, results of up to 14.2 pg/mL formoterol, 10.0 ng/mL salbutamol, and 21.4 ng/mL salbutamol-4′-O-sulfate (calculated as salbutamol equivalent) were found. In urine, maximum concentrations (after deglucuronidation) were 17.2 ng/mL formoterol, 948.5 ng/mL salbutamol, and 2738.5 ng/mL salbutamol-4′-O-sulfate. Sex-specific differences in serum concentrations as well as in urinary excretion were observed. The results pronounce the importance of the implementation and elucidation of phase II metabolites to quantitation methods in antidoping.

Background and aims Cell adhesion molecules (CAMs) are implicated in the initiation and progression of atherosclerosis, but their association with risk of type 2 diabetes remains inconsistent. This meta-analysis aimed to quantify this association with dose-response analysis in the general population without type 2 diabetes at baseline. Methods Prospective studies, investigating the association of circulating (plasma/serum) CAMs, such as intercellular adhesion molecule-1 (ICAM-1), E-selectin, vascular cell adhesion molecule-1 (VCAM-1), and P-selectin, with risk of type 2 diabetes, were included. The overall relative risks (RRs) with 95% confidence intervals (CIs) were calculated using a random-effects model. Results Sixteen datasets from 15 studies were included. The overall RR was 1.88 (95% CI 1.59 to 2.23) per 1-ln μg/ml increase in ICAM-1, and 2.44 (95% CI 1.90 to 3.12) per 1-ln μg/ml increase in E-selectin. These associations were log-linearly shaped (both pnon-linearity >0.05) and independent of traditional cardiovascular risk factors (all p Conclusions Elevated circulating CAMs, especially ICAM-1 and E-selectin, led to increased risk of type 2 diabetes in a dose-dependent manner, supporting the assumption that endothelial dysfunction contributes to the development of diabetes.

Background Evidence emerges that cardiorespiratory fitness (CRF) might be implicated in the development of heart failure (HF). This meta-analysis aimed to quantify the association between CRF exposed at baseline and HF risk with dose–response analysis and to assess whether CRF changes over time are correlated with alterations in HF risk. Methods and Results Cohort studies that assessed the association between CRF and risk of HF in subjects without baseline HF were included. Study-specific multivariate-adjusted relative risks (RRs) with 95% confidence intervals (CIs) were pooled using a random-effects model. Ten studies from 8 articles were included, enrolling 8987 incident HF cases from 154,598 participants. The RR of HF per 1-metabolic equivalent (MET) higher CRF at baseline was 0.82 (95% CI 0.80–0.84) in the overall population. The RRs were similar in men (0.82, 95% CI 0.80–0.85) and women (0.81, 95% CI 0.78–0.84), and remained minorly changed in patients with existing diabetes, hypertension, or cardiovascular disease at entry. No evidence of a nonlinear relationship between CRF at baseline and risk of HF was observed (Pnonlinearity = .18). The RR of HF per 1-MET increase in CRF over time was 0.79 (95% CI 0.67–0.93), and the measurement of CRF provided incremental value to the prediction of HF beyond conventional models. Conclusions High or increased CRF resulted in reduced risk of HF in a dose-dependent manner, supporting the necessity to increase CRF to prevent HF in clinical practice.

The purpose of this study was to investigate echocardiographic changes in left ventricular (LV) diastolic filling and left atrial (LA) strain mechanics following prolonged exercise. Ten male triathletes completed a 60-min swim, 180-min bike exercise, and a 60-min all-out run in a laboratory environment. Special attention was paid to prevent dehydration and energy deficit during the exercise protocol. All participants underwent comprehensive echocardiographic analyses of Doppler- and volumetric-derived LV diastolic filling indices and novel speckle-tracking echocardiography (STE)-derived LA strain indices. LV stroke volume (pre: 108.0±15.9 vs. post: 88.8±19.0 mL; p=0.03) and LA passive emptying volume (pre: 31.2±7.5 vs. post: 22.4±9.8 mL; p=0.05) were significantly reduced following the exercise protocol. Of the STE-derived indices of LA function, reservoir and conduit strain did not change significantly, while there was a trend towards enhanced contraction strain (pre: 15.1±3.8 vs. post: 19.4±4.8%; p=0.07). Resting heart rate was significantly higher post-exercise (53.1±5.0 vs. 81.9±16.9 bpm; p

There is growing interest in exploring circulating (plasma/serum) irisin in polycystic ovary syndrome (PCOS) patients. This meta-analysis aimed to summarize the evidence assessing circulating irisin changes in this population. A systematic search was conducted in three databases: PubMed, Cochrane Library and Web of Science, for studies reporting irisin in PCOS patients compared with healthy controls or stratified by body mass index (BMI), or assessing irisin response to hyperinsulinemia. Effect sizes (Cohen's d with 95% confidence intervals [CI]) were calculated using random-effects models. Eight studies with 918 PCOS patients and 528 healthy controls were included. Results showed that circulating irisin was higher in PCOS patients than in overall healthy controls ( d = 0.37, 95% CI 0.05 to 0.70), but not compared with BMI-matched or age- and BMI-matched controls. Circulating irisin was higher in PCOS patients with higher BMI than lower ( d = 0.36, 95% CI 0.16 to 0.56). Circulating irisin decreased 2 h later in response to euglycemic hyperinsulinemia in PCOS patients with a larger magnitude than healthy controls ( d = −0.32, 95% CI −0.53 to −0.11). In summary, with adjustment for BMI, circulating irisin in PCOS patients seems comparable to healthy controls, but its response to hyperinsulinemia might be impaired.

Background: Increased physical activity (PA) is a key element in the management of patients with nonalcoholic fatty liver disease (NAFLD); however, its association with NAFLD risk has not been systematically assessed. This meta-analysis of observational studies was to quantify this association with dose–response analysis. Methods: Electronic databases were searched to January 2017 for studies of adults reporting the risk of NAFLD in relation to PA with cohort or case-control designs. Studies that reported sex-specific data were included as separate studies. The overall risk estimates were pooled using a random-effects model, and the dose–response analysis was conducted to shape the quantitative relationship. Results: A total of 6 cohort studies from 5 articles with 32,657 incident NAFLD cases from 142,781 participants, and 4 case-control studies from 3 articles with 382 NAFLD cases and 302 controls were included. Compared with the lowest PA level, the highest PA level was associated with a risk reduction of NAFLD in cohort [RR (risk ratio) 0.79, 95% CI (confidence interval) 0.71–0.89] and case-control studies [OR (odds ratio) 0.43, 95% CI 0.27–0.68]. For cohort studies, both highest and moderate PA levels were superior to the light one in lowering NAFLD risk ( pfor interaction = 0.006 and 0.02, respectively), and there was a log-linear dose–response association ( pfor nonlinearity = 0.10) between PA and NAFLD risk [RR 0.82 (95% CI 0.73–0.91) for every 500 metabolic equivalent (MET)-minutes/week increment in PA]. Conclusions: Increased PA may lead to a reduced risk of NAFLD in a dose-dependent manner, and the current guideline-recommended minimum PA level that approximates to 500 MET-minutes/week is able to moderately reduce the NAFLD risk.

Psychosocial stress and physical, cognitive, and social activity predict the risk of cognitive decline and dementia. The aim of this study was to elucidate brain-derived neurotrophic factor (BDNF), irisin, and the kynurenine pathway (KP) as potential underlying biological correlates. We evaluated associations of irisin and the KP with BDNF in serum and with cognition, stress, and activities. Furthermore, changes in serum concentrations of BDNF, irisin, and KP metabolites were investigated after physical or cognitive training. Forty-seven older adults at risk of dementia were assigned to 10 weeks of physical training, cognitive training, or a wait-list control condition. Previous physical, cognitive, and social activities and stressful life events were recorded; global cognition, episodic memory, and executive functions were assessed. Serum levels of L-kynurenine, kynurenic acid, 3-hydroxykynurenine (3-HK), and quinolinic acid (QUIN) were determined by validated assays based on liquid chromatography coupled to tandem mass spectrometry. BDNF and irisin serum levels were determined with enzyme-linked immunosorbent assays. BDNF and irisin correlated positively with global cognition and episodic memory, while the neurotoxic metabolite QUIN correlated negatively with executive functions. Stressful life events were associated with reduced BDNF and increased 3-HK. 3-HK decreased after cognitive training, while BDNF tended to increase after physical training. This suggests that psychosocial stress as well as cognitive and physical training may impact BDNF serum levels and the KP. Irisin and QUIN may constitute novel serum biomarkers of cognitive impairment, in addition to BDNF. Larger scale trials are needed to replicate and extend these novel findings.

Objective Autonomic nervous system, especially the sympathetic nervous system, may stimulate the expression of peroxisome proliferator-activated receptor γ coactivator-1α, which regulates irisin. This study aimed to explore whether there was any association between autonomic function as assessed by heart rate related indices and irisin release following acute exercise. Subjects and methods Seventeen healthy adults were asked to perform an incremental exhaustive cycling as well as an incremental exhaustive running separately on different days. Heart rate was monitored, and blood samples were collected before, immediately, 10-, and 60-minutes post-exercise. Serum irisin was measured using ELISA kit. Results Markers for autonomic function, such as heart rate at rest, peak, or recovery, heart rate reserve, heart rate recovery, and chronotropic index, were comparable between cycling and running (all P > 0.10). Irisin was increased immediately following both exercise. No significant association was observed between heart rate at rest, peak, or recovery and irisin level at the corresponding time-point, as well as between heart rate reserve, heart rate recovery, or chronotropic index and exercise induced irisin release, with or without controlling for age, body mass index, and glucose (all P > 0.10). Conclusions Autonomic function might not be associated with irisin release in healthy adults. Arch Endocrinol Metab. 2020;64(3):201-4

Exogenous administration of recombinant irisin improves glucose metabolism. However, the association of endogenous circulating (plasma/serum) irisin with insulin resistance remains poorly delineated. This study was aimed to examine this association by meta-analyzing the current evidence without study design restriction in non-diabetic adults.Peer-reviewed studies written in English from 3 databases were searched to December 2015. Studies that reported the association between circulating irisin and insulin resistance (or its reverse, insulin sensitivity) in non-diabetic non-pregnant adults (mean ages ≥18years) were included. The pooled correlation coefficient (r) and 95% confidence intervals (CIs) were calculated using a random-effects model. Subgroup analyses and meta-regression were performed to explore potential sources of heterogeneity.Of the 195 identified publications, 17 studies from 15 articles enrolling 1912 participants reported the association between circulating irisin and insulin resistance. The pooled effect size was 0.15 (95% CI: 0.07 to 0.22) with a substantial heterogeneity (I(2)=55.5%). This association seemed to be modified by glycemic status (fasting blood glucose ≥6.1mmol/L versus6.1mmol/L) and racial-ethnic difference (Asians versus Europeans versus Americans), but not by sex difference, sampling time-point, blood sample type, ELISA kits used, baseline age, or body mass index. Circulating irisin was inversely associated with insulin sensitivity (6 studies; r=-0.17, 95% CI: -0.25 to -0.09).Circulating irisin is directly and positively associated with insulin resistance in non-diabetic adults. However, this association is rather small and requires further clarification, in particular by well-designed large epidemiological studies with overall, race-, and sex-specific analyses.

A sexual dimorphism has been reported for the adipo-myokine irisin at rest and in response to exercise. The effects of male and female sex, adiposity, and gonadectomy on irisin secretion have not been investigated before. The objective of this study was to elucidate the effects of sex, adiposity, and gonadectomy in the regulation of irisin secretion as well as PGC-1α/FNDC5 mRNA and protein expression. We hypothesized that a lack of female sex hormones by ovariectomy reduces irisin levels and inhibits skeletal muscle expression of PGC-1α and FNDC5. Circulating irisin was measured in vivo in serum samples of healthy and obese men and women at rest and in response to acute exercise. The effects of gonadectomy on serum irisin, PGC-1α and FNDC5 muscle mRNA, and protein expression were investigated in ovariectomized (OVX) and orchiectomized (ORX) Wistar rats. Serum irisin at rest was not significantly different between men and women (lean or obese). However, in response to acute aerobic exercise, irisin levels increased significantly more in lean women versus men (p ≤ 0.05). In obese individuals, resting irisin concentrations were significantly higher compared to lean subjects (p ≤ 0.001) and the irisin response to acute exercise was blunted. Only the lack of gonadal hormones in OVX but not ORX rats increased serum irisin levels (p ≤ 0.01) and resulted in significantly increased body weight (p ≤ 0.01), adipose tissue content (p ≤ 0.05), muscle FNDC5 mRNA (p ≤ 0.05), and protein (p ≤ 0.01) expression without altering PGC-1α expression. Testosterone treatment in ORX rats leads to increased PGC-1α mRNA content and reduced PGC-1α protein content without affecting FDNC5 expression or serum irisin levels. We show that a sexual dimorphism exists for the acute irisin response to exercise in normal-weight but not in obese subjects. OVX, which is associated with increased adiposity and insulin insensitivity, increases basal FNDC5 expression and serum irisin, without altering PGC-1α expression. This may be an early sign for metabolic disturbances associated with menopause, such as a developing irisin resistance or an attempt of the organism to improve glucose metabolism.

Aim Although pedometer intervention is effective in increasing physical activity among adults with Type 2 diabetes, its impact on weight loss remains unclear. This meta-analysis was aimed to assess whether pedometer intervention promotes weight loss. Methods Three different databases were searched for randomized controlled trials (RCTs) published in English up to April 2015. Studies were included if they investigated the effects of pedometer intervention on weight loss, as measured by BMI or weight. Effect sizes were aggregated using a random-effects model. Subgroup and meta-regression analyses were used to identify potential moderators. Eleven RCTs with 1258 participants were included. All enrolled participants were overweight or obese. Results Pedometer intervention led to significantly decreased BMI [weighted mean difference (WMD) −0.15 kg/m2, 95% confidence interval (CI) −0.29 to −0.02 kg/m2] and reduced weight (WMD −0.65 kg, 95% CI −1.12 to −0.17 kg). Dietary counselling seemed to be a key predictor of the observed changes. However, none of the following variables had a significant influence: step goal setting, baseline age, BMI, weight, sex distribution, disease duration, intervention duration, and baseline values or change scores for total or moderate-to-vigorous physical activity. After completion of the pedometer intervention, non-significant declines in BMI and weight were observed during the follow-up periods. Conclusions Pedometer intervention promotes modest weight loss, but its association with physical activity requires further clarification. Future studies are also required to document dietary and sedentary behaviour changes to facilitate the use of pedometers for weight loss in overweight and obese adults with Type 2 diabetes.

Objective This meta-analysis aimed to (1) quantify the association of cardiorespiratory fitness (CRF) with type 2 diabetes risk in the general population and statin users and (2) investigate the joint effects of CRF and fatness with type 2 diabetes risk. Methods Databases were searched for cohort studies reporting the association between CRF and type 2 diabetes risk. Summary hazard ratios (HRs) were obtained using random-effects models. Results Fifteen studies were included. The HRs of type 2 diabetes for every 1-metabolic equivalent increase in CRF were 0.90 (95% CI: 0.86-0.94) for the general population and 0.92 (95% CI: 0.87-0.97) for statin users, and the HRs were linearly shaped (both Pnonlinearity > 0.40). Compared with the nonstatin cohort, there was an increased risk of type 2 diabetes in statin users with the lowest and moderate CRF categories, but this was not present in the highest CRF category. The HR of type 2 diabetes for overweight/obesity-fit category versus normal weight-fit category was larger than that of the normal weight-unfit category versus the normal weight-fit category (Pinteraction = 0.004). Conclusions There was an inverse and dose-dependent association between CRF and type 2 diabetes risk. High CRF may eliminate the diabetogenic effect from statins, yet decreased body weight index seems superior in preventing type 2 diabetes.

Metabolic abnormalities and alterations in mitochondrial respiration are described in Huntington’s disease (HD). Since there is great variability concerning disease onset and progression, it is of interest to elucidate the genetic and environmental factors, such as exercise, contributing to this variability. In addition, it is unclear, if mitochondrial dysfunction become evident before onset of neurological manifestation. The aim of this study was to evaluate circulatory, cardiopulmonary and skeletal muscle metabolic responses of HD patients and age-matched controls to acute aerobic exercise. Skeletal muscle biopsies were taken from the M. vastus lateralis at rest and 3 hour after an acute bout of endurance exercise on a cycling ergometer (65% Pmax). The integrated respiratory chain function of the human quadriceps muscle vastus lateralis was measured in freshly taken fine needle biopsies by high-resolution respirometry (HRR). Preliminary results showed that the acute circulatory and skeletal muscle metabolic response to aerobic exercise appears to be blunted in HD patients vs. healthy controls. However, HRR-analysis did not show any changes in mitochondrial respiration before and after exercise comparing healthy controls and HD mutation carriers. Our data show that mitochondrial respiration can be quantified in minimal volume needle biopsies from the M. vastus lateralis of human subjects. This minimal invasive technique can be used to repeat the analysis in short time intervals. In early premanifest HD mutation carriers, mitochondrial respiration and its response to exercise is still unaffected.

High 17β-Estradiol (E2) concentrations in isolated ventricular myocytes as well as a lack of ovarian hormones in cardiac muscle of ovariectomized (OVX) rodents has been shown to lead to arrhythmogenic effects by inducing post-translational modifications, including phosphorylation of the sarcoplasmic reticulum (SR) Ca2+ release channel ryanodine receptor-2 (RyR2). The effects of estrogens on the phosphorylation status of the RyR1 in skeletal muscle have not been investigated before. Furthermore, while high intensity exercise has been shown to increase RyR phosphorylation, there is no data on the effects of moderate intensity continuous training (MICT). The aims of the study were to investigate the effects of a 3-day treatment with low (1 nM, moderate (5 nM) and high (10 nM, 100 nM) E2 concentrations on RyR1 mRNA and protein expression and phosphorylation status (pRyRSer2844) in cultured C2C12 myotubes and to study the effects of OVX on RyR1 expression and phosphorylation in rat skeletal muscle in combination with 3 weeks of MICT. Treatment with low, physiological E2 concentrations reduced dihydropyridine receptor (DHPR) and RyR1 mRNA content in C2C12 myotubes compared to untreated control cells, whereas RyR1 protein phosphorylation (pRyRSer2844) was significantly increased after treatment with high, non-physiological E2 concentrations (p ≤ 0.05). RyR1 protein content (p ≤ 0.05) and pRyRSer2844 (p ≤ 0.05) were significantly elevated in skeletal muscle of OVX vs. sham-operated rats. Importantly, pRyRSer2844 levels were similar to sham-operated controls in OVX rats after MICT (OVX vs. OVX + MICT, p ≤ 0.05). Our results indicate, that one of the actions of estrogens is to alter skeletal muscle Ca2+ homeostasis by modulating the expression and phosphorylation of the RyR1 in skeletal muscle. Notably, regular MICT was able to counteract RyR1 phosphorylation in skeletal muscle of OVX rats.

Vigorous to maximal aerobic interval training (INT) has received remarkable interest in improving cardiometabolic outcomes for type 2 diabetes patients recently, yet with inconsistent findings. This meta-analysis was aimed to quantify its effectiveness in type 2 diabetes. Randomized controlled trials (RCTs) were identified by searches of 3 databases to October 2017, which evaluated the effects of INT with a minimal training duration of 8 weeks vs. moderate-intensity continuous training (MICT) or non-exercise training (NET) among type 2 diabetes patients on outcomes including cardiorespiratory fitness, glycemic control, body composition, blood pressure, and lipid profiles. Weighted mean differences with 95% confidence intervals (CIs) were calculated with the random-effects model. Nine datasets from 7 RCTs with 189 patients were included. Compared with MICT, INT improved maximal oxygen consumption (VO2max) by 2.60 ml/kg/min (95% CI: 1.32 to 3.88 ml/kg/min, P

Aims To assess the association between attenuated heart rate recovery, a non-invasive measure of autonomic dysfunction, and risk of diabetes in the general population. Methods Databases were searched for cohort studies up to May 2017 that reported the association of heart rate recovery with the risk of diabetes. The overall hazard ratios for slowest vs fastest heart rate recovery (the referent) and for every 10-beats-per-min decrement in heart rate recovery were calculated using a random effects meta-analysis model. Results Four cohort studies with 430 incident cases of diabetes among a total of 9113 participants during a mean follow-up period of 8.1 years were included. Results showed that the slowest heart rate recovery was associated with a higher risk of diabetes (hazard ratio 1.66, 95% CI 1.16 to 2.38) vs the fastest heart rate recovery, and the hazard ratio of risk of diabetes for every 10-beats-per-min decrement in heart rate recovery was 1.29 (95% CI 1.13 to 1.48). No significant interaction effect was observed regarding the efficacy of 1-min and 2-min heart rate recovery in predicting risk of diabetes (both Pfor interaction >0.60); however, a linear dose–response relationship existed for overall studies and for studies using 1-min heart rate recovery as the exposure (both P >0.60 for non-linearity). Conclusions Attenuated heart rate recovery is associated with an increased risk of diabetes in a dose-dependent manner, and measurement of heart rate recovery is worth recommending as part of diabetes risk assessment in clinical routines. This article is protected by copyright. All rights reserved.

PGC-1α is a versatile inducer of mitochondrial biogenesis and responsive to the changing energy demands of the cell. As mitochondrial ATP production requires proteins that derive from translation products of cytosolic ribosomes, we asked whether PGC-1α directly takes part in ribosomal biogenesis. Here, we show that a fraction of cellular PGC-1α localizes to the nucleolus, the site of ribosomal transcription by RNA polymerase I. Upon activation PGC-1α associates with the ribosomal DNA and boosts recruitment of RNA polymerase I and UBF to the rDNA promoter. This induces RNA polymerase I transcription under different stress conditions in cell culture and mouse models as well as in healthy humans and is impaired already in early stages of human Huntington’s disease. This novel molecular link between ribosomal and mitochondrial biogenesis helps to explain sarcopenia and cachexia in diseases of neurodegenerative origin.

Alterations in mitochondrial respiration are an important hallmark of Huntington's disease (HD), one of the most common monogenetic causes of neurodegeneration. The ubiquitous expression of the disease causing mutant huntingtin gene raises the prospect that mitochondrial respiratory deficits can be detected in skeletal muscle. While this tissue is readily accessible in humans, transgenic animal models offer the opportunity to cross-validate findings and allow for comparisons across organs, including the brain. The integrated respiratory chain function of the human vastus lateralis muscle was measured by high-resolution respirometry (HRR) in freshly taken fine-needle biopsies from seven pre-manifest HD expansion mutation carriers and nine controls. The respiratory parameters were unaffected. For comparison skeletal muscle isolated from HD knock-in mice (HdhQ111) as well as a broader spectrum of tissues including cortex, liver and heart muscle were examined by HRR. Significant changes of mitochondrial respiration in the HdhQ knock-in mouse model were restricted to the liver and the cortex. Mitochondrial mass as quantified by mitochondrial DNA copy number and citrate synthase activity was stable in murine HD-model tissue compared to control. mRNA levels of key enzymes were determined to characterize mitochondrial metabolic pathways in HdhQ mice. We demonstrated the feasibility to perform high-resolution respirometry measurements from small human HD muscle biopsies. Furthermore, we conclude that alterations in respiratory parameters of pre-manifest human muscle biopsies are rather limited and mirrored by a similar absence of marked alterations in HdhQ skeletal muscle. In contrast, the HdhQ111 murine cortex and liver did show respiratory alterations highlighting the tissue specific nature of mutant huntingtin effects on respiration.

The fascial system builds a three-dimensional continuum of soft, collagen-containing, loose and dense fibrous connective tissue that permeates the body and enables all body systems to operate in an integrated manner. Injuries to the fascial system cause a significant loss of performance in recreational exercise as well as high-performance sports, and could have a potential role in the development and perpetuation of musculoskeletal disorders, including lower back pain. Fascial tissues deserve more detailed attention in the field of sports medicine. A better understanding of their adaptation dynamics to mechanical loading as well as to biochemical conditions promises valuable improvements in terms of injury prevention, athletic performance and sports-related rehabilitation. This consensus statement reflects the state of knowledge regarding the role of fascial tissues in the discipline of sports medicine. It aims to (1) provide an overview of the contemporary state of knowledge regarding the fascial system from the microlevel (molecular and cellular responses) to the macrolevel (mechanical properties), (2) summarise the responses of the fascial system to altered loading (physical exercise), to injury and other physiological challenges including ageing, (3) outline the methods available to study the fascial system, and (4) highlight the contemporary view of interventions that target fascial tissue in sport and exercise medicine. Advancing this field will require a coordinated effort of researchers and clinicians combining mechanobiology, exercise physiology and improved assessment technologies.

Irisin is a newly discovered hormone that is proposed to be a promising therapeutic target in obesity and type 2 diabetes. It has received remarkable attention recently, while inconsistent results have been shown regarding its association with chronic exercise training in adults. The aim of this study was to evaluate the effects of chronic exercise training on circulating (plasma/serum) irisin in adults by meta-analyzing randomized controlled trials (RCTs) and non-randomized studies (NRSs) separately. We conducted a search of the PubMed, Web of Science and Cochrane Library databases from January 2012 to September 2014 for studies published in English. Studies were included if they had an assessment of chronic (≥8 weeks) exercise training effects on circulating irisin in the general or clinical population (mean age ≥18 years) with reported outcomes of circulating irisin, and involved more than five participants. Pooled effect sizes (Cohen’s d) with 95 % confidence intervals (CIs) for changes in circulating irisin were calculated by a random-effects model. Subgroup analyses were performed to evaluate the association between exercise modes and changes in circulating irisin. Of the 181 articles screened, 12 studies in eight articles were included, of which three were RCTs and nine were NRSs. In the three RCTs (a total of 173 healthy, untrained participants), chronic exercise training was associated with a moderate and significant overall effect in decreasing circulating irisin compared with the control (d = −0.46; 95 % CI −0.76 to −0.15). Chronic resistance exercise training showed a moderate and significant effect in decreasing circulating irisin compared with the control (d = −0.41; 95 % CI −0.75 to −0.06), while endurance exercise training only had a trend (d = −0.64; 95 % CI −1.32 to 0.04). In the nine NRSs (a total of 113 intervention participants), chronic exercise training was associated with a trivial and non-significant overall effect in decreasing circulating irisin compared with baseline (d = −0.04; 95 % CI −0.30 to 0.23). Chronic exercise training leads to significantly decreased circulating irisin levels in the RCTs, while evidence remains inconclusive in the NRSs. Well-designed RCTs that measure dietary intake and report changes of body fat percentage or insulin sensitivity/resistance index following chronic exercise training are required to confirm these findings.

The ingestion of exogenous carbohydrates (CHO) during prolonged endurance exercise, such as long-distance triathlon, is considered beneficial with regard to performance. However, little is known about whether this performance benefit differs among different forms of CHO administration. To this end, the purpose of our study was to determine the impact of CHO ingestion from a semisolid source (GEL) on measures of performance and gastrointestinal (GI) comfort compared with CHO ingestion from a liquid source (LIQ). Nine well-trained triathletes participated in this randomized crossover study. Each participant completed a 60-min swim, 180-min bike exercise, and a 60-min all-out run in a laboratory environment under 2 conditions, once while receiving 67.2 ± 7.2 g · h−1 (M ± SD) of CHO from GEL and once while receiving 67.8 ± 4.2 g · h−1 of CHO from LIQ. The amount of fluid provided was matched among conditions. Respiratory exchange ratio (RER), blood glucose, and lactate as well as GI discomfort were assessed at regular intervals during the experiment. The distance covered during the final all-out run was not significantly different among participants ingesting GEL (11.81 ± 1.38 km) and LIQ (11.91 ± 1.53 km; p = .89). RER, blood glucose, and lactate did not differ significantly at any time during the experiment. Seven participants reported GI discomfort with GEL, and no athlete reported GI discomfort with LIQ (p = .016). This study suggests that administration of GEL does not alter long-distance triathlon performance when compared with LIQ, but GEL seems to be associated with reduced GI tolerance. Athletes should consider this a potential disadvantage of GEL administration during long-distance triathlon.

Over the past few years, training load and performance in competition has continuously increased and is fraught with risk to result in the accumulation of fatiguing conditions. The coach determines training success by controlling boat speed, performance, power and soft parameters like stability of rowing technique, capacity to teamwork, and mood state. However, in team sports like rowing, monitoring of individual rowers fatigue to optimize regeneration is difficult. While training should voluntarily cause acute fatigue, the accumulation of training leads to more severe fatigue, which is called “overreaching”. When fatigue is more prolonged and recovery is impaired, the condition is defined as “non-functional overreaching” ending in a primarily unexplained, long-term, and unplanned decreasing performance, a condition defined as “Unexplained Underperformance Syndrome” (UUPS) or “overtraining syndrome” (OTS). Good standards and appropriate markers for diagnosis and treatment are currently lacking.

Background: Although step counters are popularly employed for physical rehabilitation in chronic obstructive pulmonary disease (COPD) patients, their effectiveness is inconsistent and even questioned. This meta-analysis aimed to investigate whether step counter use increases physical activity or improves exercise capacity in COPD patients. Methods: Electronic databases were searched for randomized controlled trials that assessed the efficacy of step counter use in increasing physical activity or in improving exercise capacity. Data were aggregated using a random-effects model to get the overall effect sizes [standard mean difference (SMD) with 95% confidence interval (CI)], and subgroup analyses were performed. Results: A total of 15 trials enrolling 1316 patients with moderate to severe COPD were included. Step counter use increased physical activity compared with controls (SMD = 0.57, 95% CI 0.31–0.84), which is equal to a magnitude of 1026 steps/day in daily steps. It also enhanced exercise capacity with an effect size of 0.30 (95% CI 0.16–0.45), approximating to a magnitude of 11.6 m in the 6-min walking distance. Step counter use could augment physical activity (SMD = 0.64, 95% CI 0.19–1.08) and exercise capacity (SMD = 0.32, 95% CI 0.01–0.62) for patients receiving pulmonary rehabilitation. Yet it cannot enhance physical activity or exercise capacity in patients with severe COPD or among studies with intervention durations ⩾6 months (both p > 0.50). Conclusions: Step counter use increases physical activity and improves exercise capacity in COPD patients, at least in the short term, which supports the notion of recommending step counter use in COPD management.

Morphological and metabolic adaptations of the human skeletal muscle to exercise are crucial to improve performance and prevent chronic diseases and metabolic disorders. In this study we investigated human skeletal muscle protein composition in endurance trained (ET) versus untrained individuals (UT) and its modulation by an acute bout of endurance exercise. Participants were recruited based on their VO 2 max and subjected to a bicycle exercise test. M. vastus lateralis biopsies were taken before and three hours after exercise. Muscle lysates were analyzed using off-gel LC-MS/MS. Relative protein abundances were compared between ET and UT at rest and after exercise. Comparing UT and ET, we identified 92 significantly changed proteins under resting conditions. Specifically, fiber-type-specific and proteins of the oxidative phosphorylation and tricarboxylic acid cycle were increased in ET. In response to acute exercise, 71 proteins in ET and 44 in UT were altered. Here, a decrease of proteins involved in energy metabolism accompanied with alterations of heat shock and proteasomal proteins could be observed. In summary, long-term endurance training increased the basal level of structural and mitochondrial proteins in skeletal muscle. In contrast, acute exercise resulted in a depletion of proteins related to substrate utilization, especially in trained athletes. Biological significance The investigation of the human skeletal muscle proteome in response to exercise may provide novel insights into the process of muscular plasticity. It is of importance in the development of exercise-based strategies in the prevention and therapy of many chronic inflammatory and degenerative diseases which are often accompanied by muscular deconditioning. Up to date, proteomic investigations of the human muscle proteome in adaptation to exercise are mainly focused on untrained individuals and often restricted to animal studies. In the present study we compare the protein composition in endurance trained athletes and untrained individuals in the resting muscle and its modulation in response to acute exercise. To our knowledge, we present the first comprehensive analysis of skeletal muscle proteome alterations in response to acute and long-term exercise intervention.

The neurodegenerative genetic disorder of Huntington’s disease (HD) is characterised by mitochondrial impairments of the respiratory chain. The ubiquitous expression of the disease causing mutant huntingtin gene raises the question to which extent changes in mitochondrial respiration are evident in the human skeletal muscle. In addition characterisation of mitochondrial respiration in the muscle might allow conclusions about the respiratory status in the brain. The integrated respiratory chain function of the human quadriceps vastus lateralis was measured by high-resolution respirometry in fine-needle biopsies of four pre-symptomatic HD mutation carriers and seven controls. The respiratory parameters indicated a trend towards a reduction in the respiratory control ratio (RCR) of the HD carriers. In parallel, murine cortex, liver, soleus muscle and heart of male HD knock-in mice (HdhQ111), were examined by the same method. Significant changes of the respiration were restricted to the liver and the cortex. In addition mitochondrial DNA copy number and citrate synthase activity were determined to quantify the mitochondrial mass, showing no differences. From the murine tissues mRNA levels of key enzymes characterised the mitochondrial metabolic pathways. We demonstrated the feasibility to perform high-resolution respirometry measurements from small human HD muscle biopsies. Furthermore, we conclude that differences in respiratory parameters of pre-symptomatic human muscle biopsies are rather limited, which is confirmed by the analysis of murine skeletal muscle tissue. The murine cortex and liver turned out to show respiratory changes in the HdhQ111 mouse model, which indicates that respiratory capacities are different between tissues. Acknowledgement The work is supported by the research training group cellular and molecular mechanisms in ageing (CEMMA, GRK1789) which is funded by the DFG and the seed fund grant of the EINSTEIN study no 584/14 from the EHDN.

Background/aims PGC-1α is a versatile inducer of mitochondrial biogenesis and responsive to the changing energy demands of the cell. As mitochondrial ATP production requires proteins that derive from translation products of cytosolic ribosomes, we asked whether PGC-1α directly takes part in ribosomal biogenesis. Methods/techniques In a first step, we performed in vitro assays using confocal microscopy and Chromatin-immunoprecipitation in HEK and N2A cells. The results were confirmed in co-immunoprecipitation assays. Secondly, different tissues of WT and PGC-1α KO mice were investigated. To translate the in vitro data into in vivo, we cultivated primary cells of brown adipose tissue of WT and PGC-1α KO mice to reproduce the in vitro results. For translation into the human system, we investigated muscle biopsies of 21 healthy humans as well as 6 patients with Huntington’s disease. Results/outcome We show that a fraction of cellular PGC-1α localises to the nucleolus, the site of ribosomal biogenesis. Upon activation it strongly binds the ribosomal DNA and boosts recruitment of RNA polymerase I and UBF to the rDNA promoter. This induces RNA polymerase I transcription under different stress conditions in cell culture and mouse models as well as in healthy humans and is impaired already in early stages of human Huntington’s disease. Conclusions These results extend the hypothesis, that PGC-1α regulates rDNA transcription under different stress conditions to the observation that even basal levels of ribosomal biogenesis are affected by dysregulation of PGC-1α in Huntington’s disease. This novel molecular link between ribosomal and mitochondrial biogenesis helps to explain sarcopenia and cachexia in diseases of neurodegenerative origin.