Angiotensin-Converting Enzyme 2 (SARS-CoV-2 receptor) expression in human skeletal muscle.

The study aimed to determine the levels of skeletal muscle angiotensin-converting enzyme 2 (ACE2, the SARS-CoV-2 receptor) protein expression in men and women and assess whether ACE2 expression in skeletal muscle is associated with cardiorespiratory fitness and adiposity. The level of ACE2 in vastus lateralis muscle biopsies collected in previous studies from 170 men (age: 19-65 years, weight: 56-137 kg, BMI: 23-44) and 69 women (age: 18-55 years, weight: 41-126 kg, BMI: 22-39) was analyzed in duplicate by western blot. VO2 max was determined by ergospirometry and body composition by DXA. ACE2 protein expression was 1.8-fold higher in women than men (p = 0.001, n = 239). This sex difference disappeared after accounting for the percentage of body fat (fat %), VO2 max per kg of legs lean mass (VO2 max-LLM) and age (p = 0.47). Multiple regression analysis showed that the fat % (ß = 0.47) is the main predictor of the variability in ACE2 protein expression in skeletal muscle, explaining 5.2% of the variance. VO2 max-LLM had also predictive value (ß = 0.09). There was a significant fat % by VO2 max-LLM interaction, such that for subjects with low fat %, VO2 max-LLM was positively associated with ACE2 expression while as fat % increased the slope of the positive association between VO2 max-LLM and ACE2 was reduced. In conclusion, women express higher amounts of ACE2 in their skeletal muscles than men. This sexual dimorphism is mainly explained by sex differences in fat % and cardiorespiratory fitness. The percentage of body fat is the main predictor of the variability in ACE2 protein expression in human skeletal muscle.

Ultrasonographic Size of the Thenar Muscles of the Nondominant Hand Correlates with Total Body Lean Mass in Healthy Subjects.

RATIONALE AND OBJECTIVES: Sarcopenia is associated with adverse outcomes in clinical situations such as elderly population, in-hospital setting and oncologic patients. However, no direct measurement of muscular mass is routinely available for clinicians. The aim of this study was to assess the correlation between thenar musculature of the nondominant hand evaluated by ultrasound and body fat-free mass. MATERIALS AND METHODS: In this one-center, cross-sectional, observational study, the width and depth of thenar muscles of both hands was assessed by ultrasonography. Nondominant hand musculature was taken as reference as a better estimator of total body muscular mass. These data were compared to body composition by bioimpedance analysis and dual-energy X-ray absorptiometry (DXA), hand grip strength, arm muscular area and physical activity (with International Physical Activity Questionnaire ). Statistical correlation was determined for each parameter. RESULTS: We obtained ultrasonographic measurements, International Physical Activity Questionnaire and hand grip strength from 83 subjects, whereas bioimpedance was performed in 64 subjects and DXA in 29 subjects. The strongest correlations were found between longitudinal thenar depth vs fat-free mass index (fat-free mass in DXA [kg]/height2 [m]) (r = 0.63, p < 0.001, 95%CI 0.34-0.81), longitudinal depth and hand dynamometry (r = 0.72, p < 0.001, 95%CI 0.59-0.81), longitudinal depth and DXA fat-free total mass (r = 0.76, p < 0.001, 95%CI 0.54-0.88), transversal thenar depth vs fat-free mass index (r = 0.67, p < 0.001, 95%CI 0.41-0.83), transversal width and DXA fat-free total mass (r = 0.62, p < 0.001, 95%CI 0.33-0.8), transversal depth and DXA nonfat total mass (r = 0.81, p < 0.001, 95%CI 0.63-0.91). CONCLUSION: Ultrasonographic examination of the nondominant thenar musculature is a fast and simple way of assessing total body fat-free mass, showing a good correlation with body composition measured by bioimpedance analysis and DXA, hand grip strength and arm muscular area.

Enhancement of Exercise Performance by 48 Hours, and 15-Day Supplementation with Mangiferin and Luteolin in Men.

The natural polyphenols mangiferin and luteolin have free radical-scavenging properties, induce the antioxidant gene program and down-regulate the expression of superoxide-producing enzymes. However, the effects of these two polyphenols on exercise capacity remains mostly unknown. To determine whether a combination of luteolin (peanut husk extract containing 95% luteolin, PHE) and mangiferin (mango leave extract (MLE), Zynamite®) at low (PHE: 50 mg/day; and 140 mg/day of MLE containing 100 mg of mangiferin; L) and high doses (PHE: 100 mg/day; MLE: 420 mg/day; H) may enhance exercise performance, twelve physically active men performed incremental exercise to exhaustion, followed by sprint and endurance exercise after 48 h (acute effects) and 15 days of supplementation (prolonged effects) with polyphenols or placebo, following a double-blind crossover design. During sprint exercise, mangiferin + luteolin supplementation enhanced exercise performance, facilitated muscle oxygen extraction, and improved brain oxygenation, without increasing the VO2. Compared to placebo, mangiferin + luteolin increased muscle O2 extraction during post-exercise ischemia, and improved sprint performance after ischemia-reperfusion likely by increasing glycolytic energy production, as reflected by higher blood lactate concentrations after the sprints. Similar responses were elicited by the two doses tested. In conclusion, acute and prolonged supplementation with mangiferin combined with luteolin enhances performance, muscle O2 extraction, and brain oxygenation during sprint exercise, at high and low doses.

Mangifera indica L. Leaf Extract in Combination With Luteolin or Quercetin Enhances VO2peak and Peak Power Output, and Preserves Skeletal Muscle Function During Ischemia-Reperfusion in Humans.

It remains unknown whether polyphenols such as luteolin (Lut), mangiferin and quercetin (Q) have ergogenic effects during repeated all-out prolonged sprints. Here we tested the effect of Mangifera indica L. leaf extract (MLE) rich in mangiferin (Zynamite®) administered with either quercetin (Q) and tiger nut extract (TNE), or with luteolin (Lut) on sprint performance and recovery from ischemia-reperfusion. Thirty young volunteers were randomly assigned to three treatments 48 h before exercise. Treatment A: placebo (500 mg of maltodextrin/day); B: 140 mg of MLE (60% mangiferin) and 50 mg of Lut/day; and C: 140 mg of MLE, 600 mg of Q and 350 mg of TNE/day. After warm-up, subjects performed two 30 s Wingate tests and a 60 s all-out sprint interspaced by 4 min recovery periods. At the end of the 60 s sprint the circulation of both legs was instantaneously occluded for 20 s. Then, the circulation was re-opened and a 15 s sprint performed, followed by 10 s recovery with open circulation, and another 15 s final sprint. MLE supplements enhanced peak (Wpeak) and mean (Wmean) power output by 5.0-7.0% (P < 0.01). After ischemia, MLE+Q+TNE increased Wpeak by 19.4 and 10.2% compared with the placebo (P < 0.001) and MLE+Lut (P < 0.05), respectively. MLE+Q+TNE increased Wmean post-ischemia by 11.2 and 6.7% compared with the placebo (P < 0.001) and MLE+Lut (P = 0.012). Mean VO2 during the sprints was unchanged, suggesting increased efficiency or recruitment of the anaerobic capacity after MLE ingestion. In women, peak VO2 during the repeated sprints was 5.8% greater after the administration of MLE, coinciding with better brain oxygenation. MLE attenuated the metaboreflex hyperpneic response post-ischemia, may have improved O2 extraction by the Vastus Lateralis (MLE+Q+TNE vs. placebo, P = 0.056), and reduced pain during ischemia (P = 0.068). Blood lactate, acid-base balance, and plasma electrolytes responses were not altered by the supplements. In conclusion, a MLE extract rich in mangiferin combined with either quercetin and tiger nut extract or luteolin exerts a remarkable ergogenic effect, increasing muscle power in fatigued subjects and enhancing peak VO2 and brain oxygenation in women during prolonged sprinting. Importantly, the combination of MLE+Q+TNE improves skeletal muscle contractile function during ischemia/reperfusion.

What limits performance during whole-body incremental exercise to exhaustion in humans?

To determine the mechanisms causing task failure during incremental exercise to exhaustion (IE), sprint performance (10 s all-out isokinetic) and muscle metabolites were measured before (control) and immediately after IE in normoxia (P(IO2) 143 mmHg) and hypoxia (P(IO2): 73 mmHg) in 22 men (22 ± 3 years). After IE, subjects recovered for either 10 or 60 s, with open circulation or bilateral leg occlusion (300 mmHg) in random order. This was followed by a 10 s sprint with open circulation. Post-IE peak power output (W(peak)) was higher than the power output reached at exhaustion during IE (P < 0.05). After 10 and 60 s recovery in normoxia, W(peak) was reduced by 38 ± 9 and 22 ± 10% without occlusion, and 61 ± 8 and 47 ± 10% with occlusion (P < 0.05). Following 10 s occlusion, W(peak) was 20% higher in hypoxia than normoxia (P < 0.05), despite similar muscle lactate accumulation ([La]) and phosphocreatine and ATP reduction. Sprint performance and anaerobic ATP resynthesis were greater after 60 s compared with 10 s occlusions, despite the higher [La] and [H(+)] after 60 s compared with 10 s occlusion recovery (P < 0.05). The mean rate of ATP turnover during the 60 s occlusion was 0.180 ± 0.133 mmol (kg wet wt)(-1) s(-1), i.e. equivalent to 32% of leg peak O2 uptake (the energy expended by the ion pumps). A greater degree of recovery is achieved, however, without occlusion. In conclusion, during incremental exercise task failure is not due to metabolite accumulation or lack of energy resources. Anaerobic metabolism, despite the accumulation of lactate and H(+), facilitates early recovery even in anoxia. This points to central mechanisms as the principal determinants of task failure both in normoxia and hypoxia, with lower peripheral contribution in hypoxia.