The Impact of ACTN3 Gene Polymorphisms on Susceptibility to Exercise-Induced Muscle Damage and Changes in Running Economy Following Downhill Running

This study aimed to investigate if ACTN3 gene polymorphism impacts the susceptibility to exercise-induced muscle damage (EIMD) and changes in running economy (RE) following downhill running. Thirty-five healthy men were allocated to the two groups based on their ACTN3 gene variants: RR and X allele carriers. Neuromuscular function [knee extensor isometric peak torque (IPT), rate of torque development (RTD), and countermovement, and squat jump height], indirect markers of EIMD [muscle soreness, mid-thigh circumference, knee joint range of motion, and serum creatine kinase (CK) activity], and RE (oxygen uptake, minute ventilation, blood lactate concentration, and perceived exertion) for 5-min of running at a speed equivalent to 80% of individual maximal oxygen uptake speed were assessed before, immediately after, and 1–4 days after a 30-min downhill run (−15%). Neuromuscular function was compromised (P < 0.05) following downhill running with no differences between the groups, except for IPT, which was more affected in the RR individuals compared with the X allele carriers immediately (−24.9 ± 6.9% vs. −16.3 ± 6.5%, respectively) and 4 days (−16.6 ± 14.9% vs. −4.2 ± 9.5%, respectively) post-downhill running. EIMD manifested similarly for both the groups except for serum CK activity, which was greater for RR (398 ± 120 and 452 ± 126 U L–1 at 2 and 4 days following downhill running, respectively) compared with the X allele carriers (273 ± 121 and 352 ± 114 U L–1 at the same time points). RE was compromised following downhill running (16.7 ± 8.3% and 11 ± 7.5% increases in oxygen uptake immediately following downhill running for the RR and X allele carriers, respectively) with no difference between the groups. We conclude that although RR individuals appear to be more susceptible to EIMD following downhill running, this does not extend to the changes in RE.

Excessive Treadmill Training Produces different Cardiac-related MicroRNA Profiles in the Left and Right Ventricles in Mice

High-volume training followed by inadequate recovery may cause overtraining. This process may undermine the protective effect of regular exercise on the cardiovascular system and may increase the risk of pathological cardiac remodelling. We evaluated whether chronic overtraining changes cardiac-related microRNA profiles in the left and right ventricles. C57BL/6 mice were divided into the control, normal training, and overtrained by running without inclination, uphill running or downhill running groups. After an 8-week treadmill training protocol, the incremental load test and training volume results showed that the model had been successfully established. The qRT-PCR results showed increased cardiac miR-1, miR-133a, miR-133b, miR-206, miR-208b and miR-499 levels in the left ventricle of the downhill running group compared with the left ventricle of the control group. Similarly, compared with the control group, the downhill running induced increased expression of miR-21, miR-17–3p, and miR-29b in the left ventricle. Unlike the changes in the left ventricle, no difference in the expression of the tested miRNAs was observed in the right ventricle. Briefly, our results indicated that overtraining generally affects key miRNAs in the left ventricle (rather than the right ventricle) and that changes in individual miRNAs may cause either adaptive or maladaptive remodelling with overtraining.

Peripheral Alterations Affect the Loss in Force after a Treadmill Downhill Run

Downhill running has an important effect on performance in trail running competitions, but it is less studied than uphill running. The purpose of this study was to investigate the cardiorespiratory response during 15 minutes of downhill running (DR) and to evaluate the neuromuscular consequences in a group of trail runners. Before and after a 15-min DR trial (slope: −25%) at ~60% of maximal oxygen consumption (V̇O2max), we evaluated maximal voluntary contraction torque (MVCt) and muscle contractility in a group of seventeen trail running athletes. Additionally, during the DR trial, we measured V̇O2 and heart rate (HR). V̇O2 and HR increased as a function of time, reaching +19.8 ± 15.9% (p < 0.001; ES: 0.49, medium) and +15.3 ± 9.9% (p < 0.001; ES: 0.55, large), respectively, in the last minute of DR. Post-exercise, the MVCt decreased (−22.2 ± 12.0%; p < 0.001; ES = 0.55, large) with respect to the pre-exercise value. All the parameters related to muscle contractility were impaired after DR: the torque evoked by a potentiated high frequency doublet decreased (−28.5 ± 12.7%; p < 0.001; ES: 0.61, large), as did the torque response from the single-pulse stimulation (St, −41.6 ± 13.6%; p < 0.001; ES: 0.70, large) and the M-wave (−11.8 ± 12.1%; p < 0.001; ES: 0.22, small). We found that after 15 min of DR, athletes had a decreased MVCt, which was ascribed mainly to peripheral rather than central alterations. Additionally, during low-intensity DR exercise, muscle fatigue and exercise-induced muscle damage may contribute to the development of O2 and HR drift.

Internal Tibial Forces and Moments During Graded Running

The stress experienced by the tibia has contributions from the forces and moments acting on the tibia. We sought to quantify the influence of running grade on internal tibial forces and moments. Seventeen participants ran at 3.33 m/s on an instrumented treadmill at 0&#176;, &#177;5&#176;, and &#177;10&#176; while motion data were captured. Ankle joint contact force was estimated from an anthropometrically-scaled musculoskeletal model using inverse dynamics-based static optimization. Internal tibial forces and moments were quantified at the distal 1/3rd of the tibia, by ensuring static equilibrium with all applied forces and moments. Downhill running conditions resulted in lower peak internal axial force (range of mean differences: -9 to -16%, p&lt;0.001), lower peak internal anteroposterior force (-14 to -21%, p&lt;0.001), and lower peak internal mediolateral force (-14 to -15%, p&lt;0.001), compared to 0&#176; and +5&#176;. Furthermore, downhill conditions resulted in lower peak internal mediolateral moment (-11 to -21%, p&lt;0.001), lower peak internal anteroposterior moment (-13 to -14%, p&lt;0.001), and lower peak internal torsional moment (-9 to -21%, p&lt;0.001), compared to 0&#176;, +5&#176;, and +10&#176;. The +10&#176; condition resulted in lower peak internal axial force (-7 to -9%, p&lt;0.001) and lower peak internal mediolateral force (-9%, p=0.004), compared to 0&#176; and +5&#176;. These findings suggest that downhill running may be associated with lower tibial stresses than either level or uphill running.

Level, Uphill, and Downhill Running Economy Values Are Correlated Except on Steep Slopes

The aim of this study was first to determine if level, uphill, and downhill energy cost of running (ECR) values were correlated at different slopes and for different running speeds, and second, to determine the influence of lower limb strength on ECR. Twenty-nine healthy subjects completed a randomized series of 4-min running bouts on an instrumented treadmill to determine their cardiorespiratory and mechanical (i.e., ground reaction forces) responses at different constant speeds (8, 10, 12, and 14 km·h−1) and different slopes (−20, −10, −5, 0, +5, +10, +15, and +20%). The subjects also performed a knee extensor (KE) strength assessment. Oxygen and energy costs of running values were correlated between all slopes by pooling all running speeds (all r2 ≥ 0.27; p ≤ 0.021), except between the steepest uphill vs. level and the steepest downhill slope (i.e., +20% vs. 0% and −20% slopes; both p ≥ 0.214). When pooled across all running speeds, the ECR was inversely correlated with KE isometric maximal torque for the level and downhill running conditions (all r2 ≥ 0.24; p ≤ 0.049) except for the steepest downhill slope (−20%), but not for any uphill slopes. The optimal downhill grade (i.e., lowest oxygen cost) varied between running speeds and ranged from −14% and −20% (all p &lt; 0.001). The present results suggest that compared to level and shallow slopes, on steep slopes ~±20%, running energetics are determined by different factors (i.e., reduced bouncing mechanism, greater muscle strength for negative slopes, and cardiopulmonary fitness for positive slopes). On shallow negative slopes and during level running, ECR is related to KE strength.

Modulation of TRIB3 and Macrophage Phenotype to Attenuate Insulin Resistance After Downhill Running in Mice

Eccentric exercise training accompanied by a low-fat diet can prevent insulin resistance (IR) and is currently an effective method for the treatment of IR induced by high-fat diet (HFD)-associated obesity. However, the molecular mechanisms underlying this improvement of IR in adipose tissue are still not completely clear. In this study, 5–6-week-old male mice were randomly divided into a standard control diet (SCD) group (SC, n = 12) and a HFD group (HF, n = 72). After 12 weeks, 12 mice in each group were randomly sacrificed. The remaining mice in the HF group were randomly submitted to one of the following experimental protocols for 8 weeks: obesity-HFD-sedentary (OHF-Sed, n = 14), obesity-HFD-exercise (OHF-Ex, n = 16), obesity-SCD-sedentary (OSC-Sed, n = 14), and obesity-SCD-exercise (OSC-Ex, n = 16). All obese mice in the exercise group were subjected to downhill running. Half of the mice in each group received an insulin injection (0.75 U/kg) before sample collection. Epididymal fat was removed and weighed. Adipocyte size and inflammatory cell infiltration were observed by H&amp;E staining. Both basal and insulin-stimulated GLUT4 fluorescence and protein contents were detected by immunofluorescence and Western blot. Levels of IL-1β and IL-10 were detected by ELISA. Protein contents of iNOS, Arg-1, TRIB3, p-AKT, and AKT were determined by Western blot. CD86 and CD206 fluorescence were determined by immunofluorescence. The results showed that a HFD for 12 weeks induced IR accompanied by adipose tissue macrophages M1 polarization (increased iNOS protein content and CD86 fluorescence) and TRIB3-AKT activation. Downhill running accompanied by a low-fat diet attenuated IR (p &lt; 0.01), reduced inflammation levels (increased IL-10 protein content and decreased IL-1β protein content), inhibited adipose tissue macrophages M1 polarization (decreased iNOS protein content and CD86 fluorescence) and promoted M2 polarization (increased Arg-1 protein content and CD206 fluorescence), and suppressed TRIB3-AKT signaling. We concluded that downhill running accompanied by dietary fat regulation attenuates HFD-related IR in mice, which may be associated with reduced TRIB3-AKT signaling and activated M2 macrophages in adipose tissue.