Stimulated Muscle Contractions Regulate Membrane-Bound and Soluble TLR4 to Prevent LPS-Induced Signaling and Myotube Atrophy in Skeletal Muscle Cells

Toll-like receptor 4 (TLR4) activation by lipopolysaccharides (LPS) contributes to chronic inflammation and causes upregulation of muscle atrophy signaling pathways. Exercise can suppress LPS/TLR4 axis activation by reducing the expression of TLR4 on immune cells. It is unknown how this regulation occurs, and it is not clear how exercise affects TLR4 on skeletal muscle. PURPOSE: To uncover the nature and mechanisms by which exercise affects TLR4 expression and intracellular signaling using cell culture models and human experiments. METHODS: C2C12 myotubes were subjected to electrical pulse stimulation (EPS) with and without subsequent treatment with 500 ng/mL lipopolysaccharide (LPS) along with corresponding control conditions. To investigate the effect of muscle contraction on the regulation of TLR4 in-vivo, we analyzed PBMC and serum samples from eight recreationally active men that completed 60-minutes of cycling at a moderate intensity (65% of VO2max). RESULTS: In-vitro, LPS decreased membrane-bound TLR4, increased TLR4 signaling (decreased inhibitor of κBα), and induced myotube atrophy. However, stimulated muscle contractions decreased membrane-bound TLR4, increased soluble TLR4 (sTLR4), and prevented LPS-induced signaling and myotube atrophy. In human participants, a single bout of moderate-intensity exercise decreased membrane-bound TLR4 on PBMCs and increased serum-borne sTLR4. CONCLUSION: These experiments support exercise may exert a novel anti-catabolic/ anti-inflammatory effect by increasing sTLR4 and decreasing TLR4 expressed on the muscle membrane. These results could help improve interventions for conditions associated with TLR4-mediated inflammation and muscle atrophy, such as diabetes, sarcopenia, and cancer cachexia

Effects of high-intensity interval training while using a breathing-restrictive mask compared to intermittent hypobaric hypoxia

Background: Previous studies of the Elevation Training Mask (ETM) describe comparisons between groups using the ETM and controls for effects on aerobic performance. However, comparisons have not been made to intermittent hypoxic training (IHT). Further, how the ETM impacts exercise economy is unknown. Therefore, we sought to determine the effects of training with the ETM compared to IHT on aerobic performance and cycling economy. Methods: Thirty participants were randomized into an ETM, IHT, or control group (n = 10 each). Pre- and post-testing occurred using a ramp VO2max test on a cycle ergometer allowing submaximal power output (PO) measures of economy. Economy was measured using POs of 100, 125, and 150W. High-intensity cycling interval training (HIIT) occurred 2x/week for 30 min/session for six weeks. Sessions were 20 min of HIIT (30s at 100% peak power output (PPO) of pre VO2max, 90s active recovery at 25W, 10 bouts) with a 5-minute warm-up and cool-down. Repeated measures ANOVA was used for statistical analyses. RESULTS: All participants improved VO2max, PPO, and PO at ventilatory threshold 2 pre- to post-training (p < 0.05). Interactions between groups showed that the RER for the IHT group increased at 100W and 125W, and decreased at RERmax pre- to post-training while the ETM group showed the opposite response (p < 0.05). Conclusion: The ETM and IHT groups performed similarly to the control at maximal and submaximal effort following six weeks of training. The IHT group, but not the ETM group, experienced an increased glycolytic energy shift during submaximal exercise.This project was funded by the University of the New Mexico Graduate and Professional Student Association grants

Worth the wait? Time course of supine shifts in body water compartments on variables of bioelectrical impedance analysis

Bioelectrical impedance analysis (BIA) reference values are based on supine assessments. Little is known regarding the effects of time course shifts in body water compartments after assuming a supine position. The aim of this study was to characterize these effects and provide recommendations regarding the optimal waiting time to perform BIA. Thirty-eight healthy adults underwent BIA via the RJL Quantum Legacy analyzer immediately upon lying down and every 5 minutes for 15 minutes. Differences in resistance (R), reactance (Xc), intracellular (ICW), extracellular (ECW), total body water (TBW), body fat percentage (%BF), and phase angle (PhA) were assessed. There were small but significant increases in R, Xc, and %BF (all p<0.001), as well as small but significant decreases in ICW, ECW, and TBW (all p<0.001) over 15 minutes. No difference was observed for PhA (p=0.065). Average values changed over 15 minutes by +7.14Ω, +1.36Ω, -0.2L, -0.2L, -0.4L, +0.05° and +0.1% for R, Xc, ICW, ECW, TBW, PhA and %BF, respectively. BIA measurements are affected by shifts in body water compartments after assuming a supine position, but these differences lack clinical significance in healthy adults. Technicians working with healthy adults can perform BIA within 15 minutes after participants assume a supine position

Change in Exercise Performance and Markers of Acute Kidney Injury Following Heat Acclimation with Permissive Dehydration

Implementing permissive dehydration (DEH) during short-term heat acclimation (HA) may accelerate adaptations to the heat. However, HA with DEH may augment risk for acute kidney injury (AKI). This study investigated the effect of HA with permissive DEH on time-trial performance and markers of AKI. Fourteen moderately trained men (age and VO2max = 25 ± 0.5 yr and 51.6 ± 1.8 mL.kg−1.min−1) were randomly assigned to DEH or euhydration (EUH). Time-trial performance and VO2max were assessed in a temperate environment before and after 7 d of HA. Heat acclimation consisted of 90 min of cycling in an environmental chamber (40 °C, 35% RH). Neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) were assessed pre- and post-exercise on day 1 and day 7 of HA. Following HA, VO2max did not change in either group (p = 0.099); however, time-trial performance significantly improved (3%, p p = 0.485). Compared to pre-exercise, NGAL was not significantly different following day 1 and 7 of HA (p = 0.113) with no difference between groups (p = 0.667). There was a significant increase in KIM-1 following day 1 and 7 of HA (p = 0.002) with no difference between groups (p = 0.307). Heat acclimation paired with permissive DEH does not amplify improvements in VO2max or time-trial performance in a temperate environment versus EUH and does not increase markers of AKI