The Acute, Short-, and Long-Term Effects of Endurance Exercise on Skeletal Muscle Transcriptome Profiles.

A better understanding of the cellular and molecular mechanisms that are involved in skeletal muscle adaptation to exercise is fundamentally important to take full advantage of the enormous benefits that exercise training offers in disease prevention and therapy. The aim of this study was to elucidate the transcriptional signatures that distinguish the endurance-trained and untrained muscles in young adult males (24 ± 3.5 years). We characterized baseline differences as well as acute exercise-induced transcriptome responses in vastus lateralis biopsy specimens of endurance-trained athletes (ET; n = 8; VO2max, 67.2 ± 8.9 mL/min/kg) and sedentary healthy volunteers (SED; n = 8; VO2max, 40.3 ± 7.6 mL/min/kg) using microarray technology. A second cohort of SED volunteers (SED-T; n = 10) followed an 8-week endurance training program to assess expression changes of selected marker genes in the course of skeletal muscle adaptation. We deciphered differential baseline signatures that reflected major differences in the oxidative and metabolic capacity of the endurance-trained and untrained muscles. SED-T individuals in the training group displayed an up-regulation of nodal regulators of oxidative adaptation after 3 weeks of training and a significant shift toward the ET signature after 8 weeks. Transcriptome changes provoked by 1 h of intense cycling exercise only poorly overlapped with the genes that constituted the differential baseline signature of ETs and SEDs. Overall, acute exercise-induced transcriptional responses were connected to pathways of contractile, oxidative, and inflammatory stress and revealed a complex and highly regulated framework of interwoven signaling cascades to cope with exercise-provoked homeostatic challenges. While temporal transcriptional programs that were activated in SEDs and ETs were quite similar, the quantitative divergence in the acute response transcriptomes implicated divergent kinetics of gene induction and repression following an acute bout of exercise. Together, our results provide an extensive examination of the transcriptional framework that underlies skeletal muscle plasticity.

Do skeletal muscle composition and gene expression as well as acute exercise-induced serum adaptations in older adults depend on fitness status?

BACKGROUND: Inactive physical behavior among the elderly is one risk factor for cardiovascular disease, immobility and increased all-cause mortality. We aimed to answer the question whether or not circulating and skeletal muscle biomarkers are differentially expressed depending on fitness status in a group of elderly individuals. METHODS: Twenty-eight elderly individuals (73.36 ± 5.46 years) participated in this exploratory study after participating as part of the multinational SITLESS-clinical trial (implementation of self-management and exercise programs over 16 weeks). A cardiopulmonary exercise test (CPX) and resting skeletal muscle biopsy were performed to determine individual physiological performance capacity. Participants were categorized into a high physical fitness group (HPF) and a low physical fitness group (LPF) depending on peak oxygen uptake (VO2peak). Serum blood samples were taken before (pre) and after (post) CPX and were examined regarding serum BDNF, HSP70, Kynurenine, Irisin and Il-6 concentrations. Skeletal muscle tissue was analyzed by silver staining to determine the myosin heavy chain (MyHC) composition and selected genes by qRT-PCR. RESULTS: HPF showed lower body weight and body fat, while skeletal muscle mass and oxygen uptake at the first ventilatory threshold (VO2T1) did not differ between groups. There were positive associations between VO2peak and VO2VT1 in HPF and LPF. MyHC isoform quantification revealed no differences between groups. qRT-PCR showed higher expression of BDNF and BRCA1 in LPF skeletal muscle while there were no differences in other examined genes regarding energy metabolism. Basal serum concentrations of Irisin were higher in HPF compared to LPF with a trend towards higher values in BDNF and HSP70 in HPF. Increases in Il-6 in both groups were observed post. CONCLUSIONS: Although no association between muscle composition/VO2peak with fitness status in older people was detected, higher basal Irisin serum levels in HPF revealed slightly beneficial molecular serum and muscle adaptations. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02629666 . Registered 19 November 2015.

Effects of Training Status and Exercise Mode on Global Gene Expression in Skeletal Muscle.

The aim of this study was to investigate differences in skeletal muscle gene expression of highly trained endurance and strength athletes in comparison to untrained individuals at rest and in response to either an acute bout of endurance or strength exercise. Endurance (ET, n = 8, VO2max 67 ± 9 mL/kg/min) and strength athletes (ST, n = 8, 5.8 ± 3.0 training years) as well as untrained controls (E-UT and S-UT, each n = 8) performed an acute endurance or strength exercise test. One day before testing (Pre), 30 min (30'Post) and 3 h (180'Post) afterwards, a skeletal muscle biopsy was obtained from the m. vastus lateralis. Skeletal muscle mRNA was isolated and analyzed by Affymetrix-microarray technology. Pathway analyses were performed to evaluate the effects of training status (trained vs. untrained) and exercise mode-specific (ET vs. ST) transcriptional responses. Differences in global skeletal muscle gene expression between trained and untrained were smaller compared to differences in exercise mode. Maximum differences between ET and ST were found between Pre and 180'Post. Pathway analyses showed increased expression of exercise-related genes, such as nuclear transcription factors (NR4A family), metabolism and vascularization (PGC1-α and VEGF-A), and muscle growth/structure (myostatin, IRS1/2 and HIF1-α. The most upregulated genes in response to acute endurance or strength exercise were the NR4A genes (NR4A1, NR4A2, NR4A3). The mode of acute exercise had a significant effect on transcriptional regulation Pre vs. 180'Post. In contrast, the effect of training status on human skeletal muscle gene expression profiles was negligible compared to strength or endurance specialization. The highest variability in gene expression, especially for the NR4A-family, was observed in trained individuals at 180'Post. Assessment of these receptors might be suitable to obtain a deeper understanding of skeletal muscle adaptive processes to develop optimized training strategies.

Association Between Cardiorespiratory Fitness and Risk of Heart Failure: A Meta-Analysis.

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.

Preserved Left Atrial Mechanics Following a 5-h Laboratory Triathlon in Euhydrated Athletes.

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<0.001) and its change correlated strongly with depression of Doppler-derived ratio of early to late ventricular filling velocities (r=0.74, p=0.01) and reduction of LA passive emptying volume (r=0.86, p=0.01). Following prolonged exercise, LV stroke volume was reduced due to heart rate related reduction in LA passive emptying volume whereas global LA strain mechanics were not compromised in this study.

Exercise training and endothelial function in patients with type 2 diabetes: a meta-analysis.

BACKGROUND AND AIMS: Exercise training is considered a cornerstone in the management of type 2 diabetes, which is associated with impaired endothelial function. However, the association of exercise training with endothelial function in type 2 diabetes patients has not been fully understood. This meta-analysis aimed to investigate their associations with focus on exercise types. METHODS: Databases were searched up to January 2018 for studies evaluating the influences of exercise training with durations ≥ 8 weeks on endothelial function assessed by flow-mediated dilation (FMD) among type 2 diabetes patients or between type 2 diabetics and non-diabetics. Data were pooled using random-effects models to obtain the weighted mean differences (WMDs) and 95% confidence intervals (CIs). RESULTS: Sixteen databases were included. Exercise training resulted in an overall improvement in FMD by 1.77% (95% CI 0.94-2.59%) in type 2 diabetes patients. Specifically, both aerobic and combined aerobic and resistance exercise increased FMD by 1.21% (95% CI 0.23-2.19%) and 2.49% (95% CI 1.17-3.81%), respectively; but resistance exercise only showed a trend. High-intensity interval aerobic exercise did not significantly improve FMD over moderate-intensity continuous exercise. Notably, the improvement in FMD among type 2 diabetes patients was smaller compared with non-diabetics in response to exercise training (WMD - 0.72%, 95% CI - 1.36 to - 0.08%) or specifically to aerobic exercise (WMD - 0.65%, 95% CI - 1.31 to 0.01%). CONCLUSIONS: Exercise training, in particular aerobic and combined exercise, improves endothelial function in type 2 diabetes patients, but such an improvement appears to be weakened compared with non-diabetics. Trial registration PROSPERO CRD42018087376.

Circulating irisin in patients with polycystic ovary syndrome: a meta-analysis.

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.

Fascial tissue research in sports medicine: from molecules to tissue adaptation, injury and diagnostics: consensus statement.

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.

Effects of Acute Endurance Exercise on Plasma Protein Profiles of Endurance-Trained and Untrained Individuals over Time.

Acute physical exercise and repeated exercise stimuli affect whole-body metabolic and immunologic homeostasis. The aim of this study was to determine plasma protein profiles of trained (EET, n = 19) and untrained (SED, n = 17) individuals at rest and in response to an acute bout of endurance exercise. Participants completed a bicycle exercise test at an intensity corresponding to 80% of their VO2max. Plasma samples were taken before, directly after, and three hours after exercise and analyzed using multiplex immunoassays. Seventy-eight plasma variables were included in the final analysis. Twenty-nine variables displayed significant acute exercise effects in both groups. Seven proteins differed between groups, without being affected by acute exercise. Among these A2Macro and IL-5 were higher in EET individuals while leptin showed elevated levels in SED individuals. Fifteen variables revealed group and time differences with elevated levels for IL-3, IL-7, IL-10, and TNFR2 in EET individuals. An interaction effect could be observed for nine variables including IL-6, MMP-2, MMP-3, and muscle damage markers. The proteins that differ between groups indicate a long-term exercise effect on plasma protein concentrations. These findings might be of importance in the development of exercise-based strategies in the prevention and therapy of chronic metabolic and inflammatory diseases and for training monitoring.

Carbohydrate Intake in Form of Gel Is Associated With Increased Gastrointestinal Distress but Not With Performance Differences Compared With Liquid Carbohydrate Ingestion During Simulated Long-Distance Triathlon.

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.

Acute Effects of Single Versus Combined Inhaled ß2-Agonists Salbutamol and Formoterol on Time Trial Performance, Lung Function, Metabolic and Endocrine Variables.

BACKGROUND: High prevalence rates of ß2-agonist use among athletes in competitive sports makes it tempting to speculate that illegitimate use of ß2-agonists boosts performance. However, data regarding the potential performance-enhancing effects of inhaled ß2-agonists and its underlying molecular basis are scarce. METHODS: In total, 24 competitive endurance athletes (12f/12m) participated in a clinical double-blinded balanced four-way block cross-over trial to investigate single versus combined effects of ß2-agonists salbutamol (SAL) and formoterol (FOR), to evaluate the potential performance enhancement of SAL (1200 µg, Cyclocaps, Pb Pharma GmbH), FOR (36 µg, Sandoz, HEXAL AG) and SAL + FOR (1200 µg + 36 µg) compared to placebo (PLA, Gelatine capsules containing lactose monohydrate, Pharmacy of the University Hospital Ulm). Measurements included skeletal muscle gene and protein expression, endocrine regulation, urinary/serum ß2-agonist concentrations, cardiac markers, cardiopulmonary and lung function testing and the 10-min time trial (TT) performance on a bicycle ergometer as outcome variables. Blood and urine samples were collected pre-, post-, 3 h post- and 24 h post-TT. RESULTS: Mean power output during TT was not different between study arms. Treatment effects regarding lung function (p < 0.001), echocardiographic (left ventricular end-systolic volume p = 0.037; endocardial global longitudinal strain p < 0.001) and metabolic variables (e.g. NR4A2 and ATF3 pathway) were observed without any influence on performance. In female athletes, total serum ß2-agonist concentrations for SAL and FOR were higher. Microarray muscle gene analysis showed a treatment effect for target genes in energy metabolism with strongest effect by SAL + FOR (NR4A2; p = 0.001). Of endocrine variables, follicle-stimulating hormone (3 h Post-Post-TT), luteinizing hormone (3 h Post-Pre-TT) and insulin (Post-Pre-TT) concentrations showed a treatment effect (all p < 0.05). CONCLUSIONS: No endurance performance-enhancing effect for SAL, FOR or SAL + FOR within the permitted dosages compared to PLA was found despite an acute effect on lung and cardiac function as well as endocrine and metabolic variables in healthy participants. The impact of combined ß2-agonists on performance and sex-specific thresholds on the molecular and cardiac level and their potential long-term performance enhancing or health effects have still to be determined. TRIAL REGISTRATION: Registered at Eudra CT with the number: 2015-005598-19 (09.12.2015) and DRKS with number DRKS00010574 (16.11.2021, retrospectively registered).

Expression of titin-linked putative mechanosensing proteins in skeletal muscle after power resistance exercise in resistance-trained men.

Little is known about the molecular responses to power resistance exercise that lead to skeletal muscle remodeling and enhanced athletic performance. We assessed the expression of titin-linked putative mechanosensing proteins implicated in muscle remodeling: muscle ankyrin repeat proteins (Ankrd 1, Ankrd 2, and Ankrd 23), muscle-LIM proteins (MLPs), muscle RING-finger protein-1 (MuRF-1), and associated myogenic proteins (MyoD1, myogenin, and myostatin) in skeletal muscle in response to power resistance exercise with or without a postexercise meal, in fed, resistance-trained men. A muscle sample was obtained from the vastus lateralis of seven healthy men on separate days, 3 h after 90 min of rest (Rest) or power resistance exercise with (Ex + Meal) or without (Ex) a postexercise meal to quantify mRNA and protein levels. The levels of phosphorylated HSP27 (pHSP27-Ser15) and cytoskeletal proteins in muscle and creatine kinase activity in serum were also assessed. The exercise increased (P ≤ 0.05) pHSP27-Ser15 (∼6-fold) and creatine kinase (∼50%), whereas cytoskeletal protein levels were unchanged (P > 0.05). Ankrd 1 (∼15-fold) and MLP (∼2-fold) mRNA increased, whereas Ankrd 2, Ankrd 23, MuRF-1, MyoD1, and myostatin mRNA were unchanged. Ankrd 1 (∼3-fold, Ex) and MLPb (∼20-fold, Ex + Meal) protein increased, but MLPa, Ankrd 2, Ankrd 23, and the myogenic proteins were unchanged. The postexercise meal did not affect the responses observed. Power resistance exercise, as performed in practice, induced subtle early responses in the expression of MLP and Ankrd 1 yet had little effect on the other proteins investigated. These findings suggest possible roles for MLP and Ankrd 1 in the remodeling of skeletal muscle in individuals who regularly perform this type of exercise.NEW & NOTEWORTHY This is the first study to assess the early changes in the expression of titin-linked putative mechanosensing proteins and associated myogenic regulatory factors in skeletal muscle after power resistance exercise in fed, resistance-trained men. We report that power resistance exercise induces subtle early responses in the expression of Ankrd 1 and MLP, suggesting these proteins play a role in the remodeling of skeletal muscle in individuals who regularly perform this type of exercise.

Differences in Immune Response During Competition and Preparation Phase in Elite Rowers.

Background: Metabolic stress is high during training and competition of Olympic rowers, but there is a lack of biomedical markers allowing to quantify training load on the molecular level. We aimed to identify such markers applying a complex approach involving inflammatory and immunologic variables. Methods: Eleven international elite male rowers (age 22.7 ± 2.4 yrs.; VO2max 71 ± 5 ml·min-1·kg-1) of the German National Rowing team were monitored at competition phase (COMP) vs. preparation phase (PREP), representing high vs. low load. Perceived stress and recovery were assessed by a Recovery Stress Questionnaire for Athletes (RESTQ-76 Sport). Immune cell activation (dendritic cell (DC)/macrophage/monocytes/T-cells) was evaluated via fluorescent activated cell sorting. Cytokines, High-Mobility Group Protein B1 (HMGB1), cell-free DNA (cfDNA), creatine kinase (CK), uric acid (UA), and kynurenine (KYN) were measured in venous blood. Results: Rowers experienced more general stress and less recovery during COMP, but sports-related stress and recovery did not differ from PREP. During COMP, DC/macrophage/monocyte and T-regulatory cells (Treg-cell) increased (p = 0.001 and 0.010). HMGB1 and cfDNA increased in most athletes during COMP (p = 0.001 and 0.048), while CK, UA, and KYN remained unaltered (p = 0.053, 0.304, and 0.211). Pro-inflammatory cytokines IL-1ß (p = 0.002), TNF-α (p < 0.001), and the chemokine IL-8 (p = 0.001) were elevated during COMP, while anti-inflammatory Il-10 was lower (p = 0.002). Conclusion: COMP resulted in an increase in biomarkers reflecting tissue damage, with plausible evidence of immune cell activation that appeared to be compensated by anti-inflammatory mechanisms, such as Treg-cell proliferation. We suggest an anti-inflammatory and immunological matrix approach to optimize training load quantification in elite athletes.

The ELSA trial: single versus combinatory effects of non-prohibited beta-2 agonists on skeletal muscle metabolism, cardio-pulmonary function and endurance performance-study protocol for a randomized 4-way balanced cross-over trial.

BACKGROUND: Asthma and/or airway hyper-responsiveness (AHR) are common in elite endurance athletes with a high prevalence rate of beta-2 adrenoreceptor (beta-2) agonists use. Nevertheless, there are data on dose-dependent ergogenic effects of beta-2 agonists suggesting increased muscle strength, endurance and neuromuscular performance. Therefore, most beta-2 agonists belong to the World Anti Doping Agency (WADA) list of prohibited substances and it is tempting to speculate that illegitimate use of beta-2 agonists might be a common practice to boost performance in competitive sports. It is currently unknown whether or not inhaled beta-2 agonists enhance performance by stimulatory effects in skeletal and cardiac muscle. METHODS: The ELSA trial is a double-blinded, placebo-controlled, randomized, balanced, four-way cross-over study. Study participants (n=24, 12 ♀, 12 ♂) complete four study arms (i.e. periods with treatment A, placebo; B, salbutamol; C, formoterol; D, formoterol + salbutamol) in random order after an initial preliminary testing session. Participants inhale the study medication 20 min before the 10-min time trial (TT; exercise performance test), where participants cycle 10 min at the highest possible workload. Cardiac output is measured continuously. A skeletal muscle biopsy is collected 3 h after the TT. Study endpoints include measures of skeletal muscle expression of nuclear receptors, hormones and cytokine levels, urinary and plasma concentrations of salbutamol and formoterol, circulating cardiac markers, cardiopulmonary function and exercise performance (average power and peak power during the TT). Blood and urine are collected and respiratory testing is performed 24 h post TT. This clinical trial evaluates the potential performance-enhancing effects of non-prohibited, not medically indicated inhaled short- and long-acting beta-2 agonists on skeletal muscle gene expression, endocrine regulation, cardiac biomarkers, cardiopulmonary function and acute endurance exercise performance. These data will be used by WADA to adapt the annually published list of prohibited substances (WADA 2021) and will be published in scientific journals. TRIAL REGISTRATION: The trial is registered at the European Clinical Trials Database (Eudra CT) with the number: 2015-005598-19 as well as at the German register for clinical studies (DRKS number 00010574 ).

Autonomic function may not modulate irisin release in healthy adults: findings from a randomized cross-over study.

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.

Increased Hepcidin Levels During a Period of High Training Load Do Not Alter Iron Status in Male Elite Junior Rowers.

The liver-derived hormone hepcidin plays a key role in iron metabolism by mediating the degradation of the iron export protein ferroportin 1 (FPN1). Circulating levels of hepcidin and the iron storage protein ferritin are elevated during the recovery period after acute endurance exercise, which can be interpreted as an acute phase reaction to intense exercise with far-reaching consequences for iron metabolism and homeostasis. Since absolute and functional iron deficiency (ID) potentially lead to a loss of performance and well-being, it is surprising that the cumulative effects of training stress on hepcidin levels and its interplay with cellular iron availability are not well described. Therefore, the aim of this study was to determine serum levels of hepcidin at six time points during a 4-week training camp of junior world elite rowers preparing for the world championships and to relate the alterations in training load to overall iron status determined by serum ferritin, transferrin, iron, and soluble transferrin receptor (sTfR). Serum hepcidin levels increased significantly (p = 0.02) during the initial increase in training load (23.24 ± 2.43 ng/ml) at day 7 compared to the start of training camp (11.47 ± 3.92 ng/ml) and turned back on day 13 (09.51 ± 3.59 ng/ml) already, meeting well the entrance level of hepcidin at day 0. Serum ferritin was significantly higher at day 7 compared to all other timepoints with exception of the subsequent time point at day 13 reflecting well the time course pattern of hepcidin. Non-significant changes between training phases were found for serum iron, transferrin, and sTfR levels as well as for transferrin saturation, and ferritin-index (sTfR/log ferritin). Our findings indicate that hepcidin as well as ferritin, both representing acute phase proteins, are sensitive to initial increases in training load. Erythropoiesis was unaffected by iron compartmentalization through hepcidin. We conclude that hepcidin is sensitive to rigorous changes in training load in junior world elite rowers without causing short-term alterations in functional iron homeostasis.

Association between circulating cell adhesion molecules and risk of type 2 diabetes: A meta-analysis.

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 < 0.05). ICAM-1 had comparable predictive ability as E-selectin (2.22 versus 2.66, p = 0.40). However, no significant association was observed for VCAM-1 (RR 1.20, 95% CI 0.73 to 1.98) or P-selectin (RR 1.01, 95% CI 0.64 to 1.59), and the added predictive value of circulating CAMs assessed by Integrated Discrimination Improvement to the basic prediction models was small (0.01 for ICAM-1, 0.003 for E-selectin, and 0.007 for VCAM-1). 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.

Association Between Cardiorespiratory Fitness and Risk of Type 2 Diabetes: A Meta-Analysis.

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.

Using step counters to promote physical activity and exercise capacity in patients with chronic obstructive pulmonary disease: a meta-analysis.

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.

Acute exercise-induced irisin release in healthy adults: Associations with training status and exercise mode.

There is a growing interest in exploring irisin response to acute exercise; however, the associations of acute exercise-induced irisin release with training status and exercise mode are not fully understood. This study was primarily designed to evaluate these associations. Sixteen healthy adults (8 trained versus 8 untrained) underwent a bout of cycling at 80% of maximal oxygen uptake (VO2max) for 50 min, with blood drawn pre-, 10-, and 180-min post-exercise. Another 17 healthy adults performed 2 bouts of graded exercise (cycling and running) until exhaustion on separate days using a randomized cross-over design, with blood taken pre-, 0-, 10-, and 60-min post-exercise. Circulating irisin, creatine kinase (CK), aspartate aminotransferase (AST), and myoglobin (Mb) were measured, and their respective areas under the curves (AUCs) were calculated. Irisin increased 10-min after 50 min of cycling at 80% of VO2max, while its changes from baseline to post-exercise and the amount of exercise-induced irisin release (presented as AUC) were comparable between trained and untrained adults (all P > .05). Irisin remained elevated 10-min post-exhausting running but decreased towards baseline 10-min post-exhausting cycling. Exhausting running induced an increase in irisin release for the whole course of exercise and recovery periods, but cycling did not. Acute exercise-induced irisin changes seemed not related to changes of CK, aspartate AST, and Mb in general. In conclusion, acute exercise-induced irisin release is not associated with training status but might be affected by training mode. Future studies are required to investigate which exercise mode might be most efficient in altering irisin.