bims-exemet 2021-09-12 papers

Issue of 2021–09–12
five papers selected by
Javier Botella Ruiz, Victoria University

Am J Physiol Cell Physiol. 2021 Sep 08.

Discovery of Thymosin Beta-4 as a Human Exerkine and Growth Factor.

Alba Gonzalez-Franquesa, Ben Stocks, Melissa L Borg, Michael Kuefner, Emilie Dalbram, Thomas S Nielsen, Ankita Agrawal, Stanislava Pankratova, Alexander V Chibalin, Hakan K R Karlsson, Sevda Gheibi, Marie Björnholm, Niklas Rye Jørgensen, Christoffer Clemmensen, Jonas T Treebak, Morten Hostrup, Anna Krook, Juleen R Zierath, Atul S Deshmukh.

Skeletal muscle is an endocrine organ secreting exercise-induced factors (exerkines), which play a pivotal role in inter-organ crosstalk. Using mass spectrometry (MS)-based proteomics, we characterized the secretome and identified thymosin beta-4 (TMSB4X) as the most upregulated secreted protein in the media of contracting C2C12 myotubes. TMSB4X was also acutely increased in plasma of exercising humans irrespective of the insulin resistance condition or exercise mode. Treatment of mice with TMSB4X did not ameliorate the metabolic disruptions associated with diet induced-obesity, nor did it enhance muscle regeneration in vivo. However, TMSB4X increased osteoblast proliferation and neurite outgrowth, consistent with its WADA-classification as a prohibited growth factor. Therefore, we report TMSB4X as a human exerkine with a potential role in cellular crosstalk.

Keywords: exercise; exerkine; growth factors; muscle contraction; secreted factors

DOI: https://doi.org/10.1152/ajpcell.00263.2021

Front Physiol. 2021 ;12 702248

Short-Term and Lifelong Exercise Training Lowers Inflammatory Mediators in Older Men.

Lawrence D Hayes, Peter Herbert, Nicholas F Sculthorpe, Fergal M Grace.

Increased basal low-grade inflammation is observed with advancing age, which is augmented by physical inactivity. However, data regarding the influence of lifelong exercise training and particularly high-intensity interval training (HIIT) on inflammatory mediators in older men are scarce. Therefore, we examined effects of 6weeks of aerobic preconditioning followed by 6weeks of HIIT on inflammatory mediators [interleukin (IL)-6, homocysteine, and high-sensitivity C-reactive protein (hsCRP)] in previously sedentary older men (SED) and masters athletes (LEX). Further, we investigated whether SED exhibited greater basal inflammatory biomarkers compared to LEX. Twenty-two men (aged 62±2years) participated in the SED group, while 17 age-matched LEX men (aged 60±5years) also participated as a positive comparison group. In SED, preconditioning (P=0.030, d=0.34) and HIIT (P=0.030, d=0.48) caused a reduction in IL-6 compared to enrollment. SED homocysteine did not change throughout (P>0.57; d<0.26), while the decrease in hsCRP after preconditioning (P=0.486, d=0.25) and after HIIT (P=0.781, d=0.23) compared to enrollment was small. HIIT did not influence IL-6 or hsCRP in LEX (all P>0.42; d<0.3). Homocysteine increased from enrollment to post-HIIT in LEX (P=0.144, d=0.83), but all other perturbations were trivial. IL-6 and hsCRP were greater in SED than LEX throughout the investigation (all P<0.029; d>0.72), but homocysteine was not different (all P >0.131; d<0.41). Results of this study suggest moderate-intensity aerobic exercise and HIIT lowers IL-6 (and possible hsCRP) in previously sedentary older men. Moreover, lifelong exercise is associated with reduced concentrations of some inflammatory biomarkers in older males, and therefore, physical activity, rather than age per se, is implicated in chronic low-grade inflammation. Moreover, physical inactivity-induced inflammation may be partly salvaged by short-term exercise training.

Keywords: Aging; C-reactive protein; high-intensity interval training; homocysteine; inflammaging; inflammation; interleukin-6

DOI: https://doi.org/10.3389/fphys.2021.702248

Proc Natl Acad Sci U S A. 2021 Sep 14. pii: e2025932118. [Epub ahead of print]118(37):

Mitochondria-localized AMPK responds to local energetics and contributes to exercise and energetic stress-induced mitophagy.

Mitochondria form a complex, interconnected reticulum that is maintained through coordination among biogenesis, dynamic fission, and fusion and mitophagy, which are initiated in response to various cues to maintain energetic homeostasis. These cellular events, which make up mitochondrial quality control, act with remarkable spatial precision, but what governs such spatial specificity is poorly understood. Herein, we demonstrate that specific isoforms of the cellular bioenergetic sensor, 5' AMP-activated protein kinase (AMPKα1/α2/β2/γ1), are localized on the outer mitochondrial membrane, referred to as mitoAMPK, in various tissues in mice and humans. Activation of mitoAMPK varies across the reticulum in response to energetic stress, and inhibition of mitoAMPK activity attenuates exercise-induced mitophagy in skeletal muscle in vivo. Discovery of a mitochondrial pool of AMPK and its local importance for mitochondrial quality control underscores the complexity of sensing cellular energetics in vivo that has implications for targeting mitochondrial energetics for disease treatment.

Keywords: AMPK; exercise; mitochondria; mitophagy; skeletal muscle

DOI: https://doi.org/10.1073/pnas.2025932118

Front Physiol. 2021 ;12 715881

HIIT'ing or MISS'ing the Optimal Management of Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis of High- Versus Moderate-Intensity Exercise Prescription.

Cory T Richards, Victoria L Meah, Philip E James, D Aled Rees, Rachel N Lord.

Introduction: Polycystic Ovary syndrome (PCOS) is a metabolic disorder associated with increased cardiovascular disease risk. Exercise is an effective treatment strategy to manage symptoms and reduce long-term health risk. High-intensity interval training (HIIT) has been suggested as a more efficient exercise mode in PCOS; however, it is not clear whether HIIT is superior to moderate intensity steady state exercise (MISS). Methods: We synthesized available data through a systematic review and meta-analysis to compare the effectiveness of isolated HIIT and MISS exercise interventions. Our primary outcome measures were cardiorespiratory fitness and insulin resistance, measured using V˙ O2max and HOMA-IR respectively. Results: A total of 16 studies were included. Moderate-quality evidence from 16 studies identified significant improvements in V˙ O2max following MISS (Δ = 1.081 ml/kg/min, p < 0.001, n = 194), but not HIIT (Δ = 0.641 ml/kg/min, p = 0.128, n = 28). Neither HIIT nor MISS improved HOMA-IR [(Δ = -0.257, p = 0.374, n = 60) and (Δ = -0.341, p = 0.078, n = 159), respectively]. Discussion: A significant improvement in V˙ O2max was evident following MISS, but not HIIT exercise in women with PCOS. This contrasts with previous literature in healthy and clinical cohorts that report superior benefits of HIIT. Therefore, based on available moderate-quality evidence, HIIT exercise does not provide superior outcomes in V˙ O2max compared with MISS, although larger high-quality interventions are needed to fully address this. Additional dietary/pharmacological interventions may be required in conjunction with exercise to improve insulin sensitivity.

Keywords: PCOS; cardiometabolic risk; cardiorespiratory fitness; exercise; high-intensity; insulin resistance; moderate-intensity

DOI: https://doi.org/10.3389/fphys.2021.715881

Eur J Prev Cardiol. 2021 Sep 11. pii: zwab151. [Epub ahead of print]

miR-181c level predicts response to exercise training in patients with heart failure and preserved ejection fraction: an analysis of the OptimEx-Clin trial.

OptimEx-Clin Study Group

AIMS: In patients with heart failure with preserved ejection fraction (HFpEF), exercise training improves the quality of life and aerobic capacity (peakV·O2). Up to 55% of HF patients, however, show no increase in peakV·O2 despite adequate training. We hypothesized that circulating microRNAs (miRNAs) can distinguish exercise low responders (LR) from exercise high responders (HR) among HFpEF patients.
METHODS AND RESULTS: We selected HFpEF patients from the Optimizing Exercise Training in Prevention and Treatment of Diastolic HF (OptimEx) study which attended ≥70% of training sessions during 3 months (n = 51). Patients were defined as HR with a change in peakV·O2 above median (6.4%), and LR as below median (n = 30 and n = 21, respectively). Clinical, ergospirometric, and echocardiographic characteristics were similar between LR and HR. We performed an miRNA array (n = 377 miRNAs) in 14 age- and sex-matched patients. A total of 10 miRNAs were upregulated in LR, of which 4 correlated with peakV·O2. Validation in the remaining 37 patients indicated that high miR-181c predicted reduced peakV·O2 response (multiple linear regression, β = -2.60, P = 0.011), and LR status (multiple logistic regression, odds ratio = 0.48, P = 0.010), independent of age, sex, body mass index, and resting heart rate. Furthermore, miR-181c decreased in LR after exercise training (P-group = 0.030, P-time = 0.048, P-interaction = 0.037). An in silico pathway analysis identified several downstream targets involved in exercise adaptation.
CONCLUSIONS: Circulating miR-181c is a marker of the response to exercise training in HFpEF patients. High miR-181c levels can aid in identifying LR prior to training, providing the possibility for individualized management.

Keywords: Epigenetics; HFpEF; MicroRNA; Peak aerobic capacity

DOI: https://doi.org/10.1093/eurjpc/zwab151