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To elucidate the molecular mechanisms behind physical inactivity-induced insulin resistance in skeletal muscle, 12 young, healthy male subjects completed 7 days of bed rest with vastus lateralis muscle biopsies obtained before and after. In six of the subjects, muscle biopsies were taken from both legs before and after a 3-h hyperinsulinemic euglycemic clamp performed 3 h after a 45-min, one-legged exercise. Blood samples were obtained from one femoral artery and both femoral veins before and during the clamp. Glucose infusion rate and leg glucose extraction during the clamp were lower after than before bed rest. This bed rest-induced insulin resistance occurred together with reduced muscle GLUT4, hexokinase II, protein kinase B/Akt1, and Akt2 protein level, and a tendency for reduced 3-hydroxyacyl-CoA dehydrogenase activity. The ability of insulin to phosphorylate Akt and activate glycogen synthase (GS) was reduced with normal GS site 3 but abnormal GS site 2+2a phosphorylation after bed rest. Exercise enhanced insulin-stimulated leg glucose extraction both before and after bed rest, which was accompanied by higher GS activity in the prior-exercised leg than the rested leg. The present findings demonstrate that physical inactivity-induced insulin resistance in muscle is associated with lower content/activity of key proteins in glucose transport/phosphorylation and storage. [ABSTRACT FROM AUTHOR]

The tibialis anterior muscle plays a critical role in human ambulation and contributes to maintaining the upright posture. However, little is known about its muscle architecture in males and females. One hundred and nine physically active males and females were recruited. Tibialis anterior muscle thickness, pennation angle, and fascicle length were measured at rest in both unipennate regions of both legs using real-time ultrasound imaging. A linear mixed model was used with muscle thickness, pennation angle, or fascicle length as the dependent variables. All models were carried out with and without total leg lean mass and shank length as covariates. Causal mediation analysis was computed to explore the effect of muscle thickness on the relationship between fascicle length and pennation angle. There were no significant differences between dominant and nondominant legs regarding muscle architecture. Muscle thickness and pennation angle were greater in the deep than the superficial unipennate region in males (1.9 mm and 1.1°, p < 0.001) and women (3.4 mm and 2.2°, p < 0.001). However, the fascicle length was similar in both regions for both sexes. The differences remained significant after accounting for differences in leg lean mass and shank length. In both regions, muscle thickness was 1-3 mm greater in males and superficial pennation angle 2° smaller in females (both, p < 0.001). After accounting for leg lean mass and shank length, sex differences remained for muscle thickness (1.6 mm, p < 0.05) and pennation angle (3.4°, p < 0.001) but only in the superficial region. In both regions, leg lean mass and shank-adjusted fascicle length were 1.4 mm longer in females than males (p < 0.05). The causal mediation analysis revealed that the estimation of fascicle length was positive, suggesting that a 10% increase in muscle thickness would augment the fascicle length, allowing a 0.38° pennation angle decrease. Moreover, the pennation angle increases in total by 0.54° due to the suppressive effect of the increase in fascicle length. The estimated mediation, direct, and total effects were all significantly different from zero (p < 0.001). Overall, our results indicate that the architectural anatomy of the tibialis anterior shows sexual dimorphism in humans. Tibialis anterior presents morphological asymmetries between superficial and deep unipennate regions in both sexes. Lastly, our causal mediation model identified a suppressive effect of fascicle length on the pennation angle, suggesting that increments in muscle thickness are not always aligned with increments in fascicle length or the pennation angle., (© 2023 The Authors. Journal of Anatomy published by John Wiley & Sons Ltd on behalf of Anatomical Society.)

Cerebral blood flow (CBF) is regulated to secure brain O 2 delivery while simultaneously avoiding hyperperfusion; however, both requisites may conflict during sprint exercise. To determine whether brain O 2 delivery or CBF is prioritized, young men performed sprint exercise in normoxia and hypoxia (P I O 2  = 73 mmHg). During the sprints, cardiac output increased to ∼22 L min -1 , mean arterial pressure to ∼131 mmHg and peak systolic blood pressure ranged between 200 and 304 mmHg. Middle-cerebral artery velocity (MCAv) increased to peak values (∼16%) after 7.5 s and decreased to pre-exercise values towards the end of the sprint. When the sprints in normoxia were preceded by a reduced P ET CO 2 , CBF and frontal lobe oxygenation decreased in parallel ( r = 0.93, P < 0.01). In hypoxia, MCAv was increased by 25%, due to a 26% greater vascular conductance, despite 4-6 mmHg lower PaCO 2 in hypoxia than normoxia. This vasodilation fully accounted for the 22 % lower CaO 2 in hypoxia, leading to a similar brain O 2 delivery during the sprints regardless of P I O 2 . In conclusion, when a conflict exists between preserving brain O 2 delivery or restraining CBF to avoid potential damage by an elevated perfusion pressure, the priority is given to brain O 2 delivery.

Introduction: Androgens play a major role in fat oxidation; however, the effects of androgens depend, among other factors, on the intrinsic characteristics of the androgen receptor (AR). Lower repetitions of CAG and GGN polymorphism appear to have a protective effect on fat accumulation in the transition from adolescent to mid-twenties. Whether a similar protective effect is present later in life remains unknown. The aims of this study were: a) to evaluate if extreme CAG and GGN repeat polymorphisms of the androgen receptors influence body fat mass, its regional distribution, resting metabolic rate (RMR), maximal fat oxidation capacity (MFO) and serum leptin, free testosterone and osteocalcin in healthy adult men; and b) to determine the longitudinal effects on fat tissue accumulation after 6.4 years of follow-up., Methods: CAG and GGN repeats length were measured in 319 healthy men (mean ± standard deviation [SD]: 28.3 ± 7.6 years). From these, we selected the subjects with extreme short (CAGS < or equal 19; n = 7) and long (CAGL > or equal 24; n = 10) CAG repeats, and the subjects with short (GGNS < or equal to 22; n = 9) and long (GGNL > or equal to 25; n = 10) GGN repeats. Body composition was assessed by DXA and serum levels of leptin, free testosterone and osteocalcin by ELISA. After 6.4 years of follow-up, DXA was repeated, and resting metabolic rate (RMR), MFO and VO2max determined by indirect calorimetry., Results: CAGS and CAGL subjects had similar RMR and accumulated comparable amounts of fat tissue over 6.4 ± 1.0 years of follow-up. However, CAGL had higher MFO and total lean mass than CAGS (p < 0.05). Men with GGNS accumulated greater amount of total fat mass than men with GGNL, particularly in the trunk region seven years later. This concurred with a greater MFO in the GGNL group (p < 0.05), who accumulated less fat mass. Free testosterone was associated with MFO in absolute values (r = 0.45; p < 0.05) and MFO per kg of lower extremity lean mass per height squared (r = 0.35; p < 0.05)., Conclusiones: CAG and GGN repeat polymorphisms may influence muscle fat oxidation capacity and may have a role in the accumulation of fat over the years.

The effects of exercise on the core musculature have not been investigated in prepubescents. The main purpose of the present study was to determine the volume and degree of asymmetry of rectus abdominis, obliques and transversus abdominis, quadratus lumborum, iliopsoas, gluteus and paravertebralis muscles in prepubescent tennis players and in untrained boys. The muscle volume was determined using magnetic resonance imaging (MRI) in 7 male prepubescent tennis players and 10 untrained controls (mean age 11.0 ± 0.8 years, Tanner 1-2). After accounting for height and body weight as covariates, the tennis players had 14-34% greater volume than the controls in all the muscles analysed (P < 0.05) except in paravertebralis, dominant quadratus lumborum and non-dominant gluteus, which had similar volumes in both groups (P = NS). Compared to controls, the tennis players displayed a greater degree of asymmetry in quadratus lumborum and rectus abdominis (3% vs. 15%, P < 0.01 and 8% vs. 17%, P = 0.06, respectively). The level of asymmetry of obliques and transversus abdominis, iliopsoas, gluteus and paravertebralis muscles was similar in both groups (P = NS). In conclusion, tennis playing at prepubertal ages induces a selective hypertrophy of the core musculature and exaggerates the degree of asymmetry of quadratus lumborum and rectus abdominis compared to untrained boys.

Background: Shorter CAG and GGN androgen receptor (AR) repeat polymorphisms are associated with stronger androgen signaling, and therefore, could influence lean mass and exercise performance during growth., Methods: Physical fitness and body composition were measured by standardized procedures and the length of CAG and GGN repeats was determined by PCR and fragment analysis in 152 boys (11.5±2.6 years; Tanner ≤5) and 116 girls (10.1±3.2 years; Tanner ≤5). Individuals were grouped as CAG short (CAGS) if harboring repeat lengths of ≤21 and CAG long (CAGL) if CAG >21. Moreover, subjects were grouped as GGN short (GGNS) if harboring repeat lengths of ≤23 and GGN long (GGNL) if GGN>23., Results: No significant differences in anthropometrics and body composition were observed between either CAGS and CAGL groups and GGNS and GGNL groups. Boys harboring CAGS completed the 300-meter test faster than their CAGL counterparts. Moreover, girls from the GGNL group showed a significant higher VO2max than those in the GGNS group., Conclusions: In summary, carrying a short allele of the androgen receptor CAG repeat polymorphism is associated to higher anaerobic performance in boys, whereas long alleles of androgen receptor GGN polymorphisms are associated to higher aerobic capacity in girls.

To determine the influence of androgen receptor CAG and GGN repeat polymorphisms on fat mass and maximal fat oxidation (MFO), CAG and GGN repeat lengths were measured in 128 young boys, from which longitudinal data were obtained in 45 of them [mean ± SD: 12.8 ± 3.6 years old at recruitment, and 27.0 ± 4.8 years old at adult age]. Subjects were grouped as CAG short (CAG S ) if harboring repeat lengths ≤  21, the rest as CAG long (CAG L ); and GGN short (GGN S ) if GGN repeat lengths ≤  23, or long if >  23 (GGN L ). CAG S and GGN S were associated with lower adiposity than CAG L or GGN L (P < 0.05). There was an association between the logarithm of CAG repeats polymorphism and the changes of body mass (r = 0.34, P = 0.03). At adult age, CAG S men showed lower accumulation of total body and trunk fat mass, and lower resting metabolic rate (RMR) and MFO per kg of total lean mass compared with CAG L (P < 0.05). GGN S men also showed lower percentage of body fat (P < 0.05). In summary, androgen receptor CAG and GGN repeat polymorphisms are associated with RMR, MFO, fat mass, and its regional distribution in healthy male adolescents, influencing fat accumulation from adolescence to adult age., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

It is generally accepted that preadolescents have a limited capacity to develop muscle hypertrophy in response to exercise compared with older populations; however, studies are scarce and conflicting. The main aim of the present study was to assess if playing tennis is associated with the hypertrophy of dominant pectoralis muscles (PM) in professional (PRO) and in prepubescent tennis players (PRE). A secondary aim was to assess if the degree of asymmetry of PM is greater in PRO than PRE. The volume of PM of both sides was determined using magnetic resonance imaging in 8 male PRO (21.9 years), 6 male PRE (11 years, Tanner 1-2) and 12 male non-active controls (6 adults: 23.5 years; and 6 prepubescents: 10.7 years, Tanner 1-2). PRO and PRE had 15 and 30% greater volume, respectively, in the dominant than in the contralateral PM (P < .01). No significant side-to-side differences in PM volume were observed in the non-active controls (3%, P = .34 in adults and 5%, P = .17 in children). The degree of side-to-side asymmetry in PM volume was greater in PRE than in PRO (P < .05). In conclusion, tennis practice is associated with marked hypertrophy of dominant PM in tennis players, even at prepubertal age, whilst non-active age-matched control subjects display similar volumes in both sides. The larger asymmetry observed in PRE than in PRO may indicate a greater relative loading in the children or increased contralateral hypertrophy in the professionals. This study demonstrates that prepubertal children respond with marked hypertrophy to loading by tennis.

To elucidate the mechanisms underlying the differences in adaptation of arm and leg muscles to sprint training, over a period of 11 days 16 untrained men performed six sessions of 4-6 × 30-s all-out sprints (SIT) with the legs and arms, separately, with a 1-h interval of recovery. Limb-specific VO 2 peak, sprint performance (two 30-s Wingate tests with 4-min recovery), muscle efficiency and time-trial performance (TT, 5-min all-out) were assessed and biopsies from the m. vastus lateralis and m. triceps brachii taken before and after training. VO 2 peak and Wmax increased 3-11% after training, with a more pronounced change in the arms ( P < 0.05). Gross efficiency improved for the arms (+8.8%, P < 0.05), but not the legs (-0.6%). Wingate peak and mean power outputs improved similarly for the arms and legs, as did TT performance. After training, VO 2 during the two Wingate tests was increased by 52 and 6% for the arms and legs, respectively ( P < 0.001). In the case of the arms, VO 2 was higher during the first than second Wingate test (64 vs. 44%, P < 0.05). During the TT, relative exercise intensity, HR, VO 2 , VCO 2 , V E , and V t were all lower during arm-cranking than leg-pedaling, and oxidation of fat was minimal, remaining so after training. Despite the higher relative intensity, fat oxidation was 70% greater during leg-pedaling ( P = 0.017). The aerobic energy contribution in the legs was larger than for the arms during the Wingate tests, although VO 2 for the arms was enhanced more by training, reducing the O 2 deficit after SIT. The levels of muscle glycogen, as well as the myosin heavy chain composition were unchanged in both cases, while the activities of 3-hydroxyacyl-CoA-dehydrogenase and citrate synthase were elevated only in the legs and capillarization enhanced in both limbs. Multiple regression analysis demonstrated that the variables that predict TT performance differ for the arms and legs. The primary mechanism of adaptation to SIT by both the arms and legs is enhancement of aerobic energy production. However, with their higher proportion of fast muscle fibers, the arms exhibit greater plasticity.

End-tidal PCO2 (PET CO2 ) has been used to estimate arterial pressure CO2 (Pa CO2 ). However, the influence of blood temperature on the Pa CO2 has not been taken into account. Moreover, there is no equation validated to predict Pa CO2 during exercise in severe acute hypoxia. To develop a new equation to predict temperature-corrected Pa CO2 values during exercise in normoxia and severe acute hypoxia, 11 volunteers (21.2 ± 2.1 years) performed incremental exercise to exhaustion in normoxia (Nox, PI O2 : 143 mmHg) and hypoxia (Hyp, PI O2 : 73 mmHg), while arterial blood gases and temperature (ABT) were simultaneously measured together with end-tidal PCO2 (PET CO2 ). The Jones et al. equation tended to underestimate the temperature corrected (tc) Pa CO2 during exercise in hypoxia, with greater deviation the lower the Pa CO2 tc (r = 0.39, P < 0.05). The new equation has been developed using a random-effects regression analysis model, which allows predicting Pa CO2 tc both in normoxia and hypoxia: Pa CO2 tc = 8.607 + 0.716 × PET CO2 [R(2)  = 0.91; intercept SE = 1.022 (P < 0.001) and slope SE = 0.027 (P < 0.001)]. This equation may prove useful in noninvasive studies of brain hemodynamics, where an accurate estimation of Pa CO2 is needed to calculate the end-tidal-to-arterial PCO2 difference, which can be used as an index of pulmonary gas exchange efficiency., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

To determine the level of hypoxia from which muscle activation (MA) is reduced during incremental exercise to exhaustion (IE), and the role played by PIO2 in this process, ten volunteers (21 ± 2 years) performed four IE in severe acute hypoxia (SAH) (PIO2 = 73 mmHg). Upon exhaustion, subjects were asked to continue exercising while the breathing gas mixture was swiftly changed to a placebo (73 mmHg) or to a higher PIO2 (82, 92, 99, and 142 mmHg), and the IE continued until a new exhaustion. At the second exhaustion, the breathing gas was changed to room air (normoxia) and the IE continued until the final exhaustion. MA, as reflected by the vastus medialis (VM) and lateralis (VL) EMG raw and normalized root mean square (RMSraw, and RMSNz, respectively), normalized total activation index (TAINz), and burst duration were 8-20% lower at exhaustion in SAH than in normoxia (P < 0.05). The switch to a placebo or higher PIO2 allowed for the continuation of exercise in all instances. RMSraw, RMSNz, and TAINz were increased by 5-11% when the PIO2 was raised from 73 to 92, or 99 mmHg, and VL and VM averaged RMSraw by 7% when the PIO2 was elevated from 73 to 142 mmHg (P < 0.05). The increase of VM-VL average RMSraw was linearly related to the increase in PIO2, during the transition from SAH to higher PIO2 (R (2) = 0.915, P < 0.05). In conclusion, increased PIO2 at exhaustion reduces fatigue and allows for the continuation of exercise in moderate and SAH, regardless of the effects of PIO2 on MA. At task failure, MA is increased during the first 10 s of increased PIO2 when the IE is performed at a PIO2 close to 73 mmHg and the PIO2 is increased to 92 mmHg or higher. Overall, these findings indicate that one of the central mechanisms by which severe hypoxia may cause central fatigue and task failure is by reducing the capacity for reaching the appropriate level of MA to sustain the task. The fact that at exhaustion in severe hypoxia the exercise was continued with the placebo-gas mixture demonstrates that this central mechanism has a cognitive component.

To determine the accuracy and precision of constant infusion transpulmonary thermodilution cardiac output (CITT-Q) assessment during exercise in humans, using indocyanine green (ICG) dilution and bolus transpulmonary thermodilution (BTD) as reference methods, cardiac output (Q) was determined at rest and during incremental one- and two-legged pedaling on a cycle ergometer, and combined arm cranking with leg pedaling to exhaustion in 15 healthy men. Continuous infusions of iced saline in the femoral vein (n = 41) or simultaneously in the femoral and axillary (n = 66) veins with determination of temperature in the femoral artery were used for CITT-Q assessment. CITT-Q was linearly related to ICG-Q (r = 0.82, CITT-Q = 0.876 × ICG-Q + 3.638, P < 0.001; limits of agreement ranging from -1.43 to 3.07 L/min) and BTD-Q (r = 0.91, CITT-Q = 0.822 × BTD + 4.481 L/min, P < 0.001; limits of agreement ranging from -1.01 to 2.63 L/min). Compared with ICG-Q and BTD-Q, CITT-Q overestimated cardiac output by 1.6 L/min (≈ 10% of the mean ICG and BTD-Q values, P < 0.05). For Q between 20 and 28 L/min, we estimated an overestimation < 5%. The coefficient of variation of 23 repeated CITT-Q measurements was 6.0% (CI: 6.1-11.1%). In conclusion, cardiac output can be precisely and accurately determined with constant infusion transpulmonary thermodilution in exercising humans., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Reports concerning the effect of endurance exercise on the anabolic response to strength training have been contradictory. This study re-investigated this issue, focusing on training effects on indicators of protein synthesis and degradation. Two groups of male subjects performed 7 weeks of resistance exercise alone (R; n = 7) or in combination with preceding endurance exercise, including both continuous and interval cycling (ER; n = 9). Muscle biopsies were taken before and after the training period. Similar increases in leg-press 1 repetition maximum (30%; P<0.05) were observed in both groups, whereas maximal oxygen uptake was elevated (8%; P<0.05) only in the ER group. The ER training enlarged the areas of both type I and type II fibers, whereas the R protocol increased only the type II fibers. The mean fiber area increased by 28% (P<0.05) in the ER group, whereas no significant increase was observed in the R group. Moreover, expression of Akt and mTOR protein was enhanced in the ER group, whereas only the level of mTOR was elevated following R training. Training-induced alterations in the levels of both Akt and mTOR protein were correlated to changes in type I fiber area (r = 0.55-0.61, P<0.05), as well as mean fiber area (r = 0.55-0.61, P<0.05), reflecting the important role played by these proteins in connection with muscle hypertrophy. Both training regimes reduced the level of MAFbx protein (P<0.05) and tended to elevate that of MuRF-1. The present findings indicate that the larger hypertrophy observed in the ER group is due more to pronounced stimulation of anabolic rather than inhibition of catabolic processes.

To determine whether task failure during incremental exercise to exhaustion (IE) is principally due to reduced neural drive and increased metaboreflex activation eleven men (22 ± 2 years) performed a 10 s control isokinetic sprint (IS; 80 rpm) after a short warm-up. This was immediately followed by an IE in normoxia (Nx, PIO2:143 mmHg) and hypoxia (Hyp, PIO2:73 mmHg) in random order, separated by a 120 min resting period. At exhaustion, the circulation of both legs was occluded instantaneously (300 mmHg) during 10 or 60 s to impede recovery and increase metaboreflex activation. This was immediately followed by an IS with open circulation. Electromyographic recordings were obtained from the vastus medialis and lateralis. Muscle biopsies and blood gases were obtained in separate experiments. During the last 10 s of the IE, pulmonary ventilation, VO2, power output and muscle activation were lower in hypoxia than in normoxia, while pedaling rate was similar. Compared to the control sprint, performance (IS-Wpeak) was reduced to a greater extent after the IE-Nx (11% lower P < 0.05) than IE-Hyp. The root mean square (EMGRMS) was reduced by 38 and 27% during IS performed after IE-Nx and IE-Hyp, respectively (Nx vs. Hyp: P < 0.05). Post-ischemia IS-EMGRMS values were higher than during the last 10 s of IE. Sprint exercise mean (IS-MPF) and median (IS-MdPF) power frequencies, and burst duration, were more reduced after IE-Nx than IE-Hyp (P < 0.05). Despite increased muscle lactate accumulation, acidification, and metaboreflex activation from 10 to 60 s of ischemia, IS-Wmean (+23%) and burst duration (+10%) increased, while IS-EMGRMS decreased (-24%, P < 0.05), with IS-MPF and IS-MdPF remaining unchanged. In conclusion, close to task failure, muscle activation is lower in hypoxia than in normoxia. Task failure is predominantly caused by central mechanisms, which recover to great extent within 1 min even when the legs remain ischemic. There is dissociation between the recovery of EMGRMS and performance. The reduction of surface electromyogram MPF, MdPF and burst duration due to fatigue is associated but not caused by muscle acidification and lactate accumulation. Despite metaboreflex stimulation, muscle activation and power output recovers partly in ischemia indicating that metaboreflex activation has a minor impact on sprint performance.

Objectives: This study was designed to investigate the association of gender, fibre type composition, and anaerobic performance with the basal skeletal muscle signalling cascades regulating muscle phenotype., Design: Muscle biopsies were obtained from 25 men and 10 women all young and healthy., Methods: Protein phosphorylation of Thr(172)AMPKα, Ser(221)ACCβ, Thr(286)CaMKII as well as total protein abundance of PGC-1α, SIRT1, and CnA were measured by Western blot and anaerobic performance by the Wingate test., Results: Percent type I myosin heavy chain (MHC I) was lower in men (37.1 ± 10.4 vs. 58.5 ± 12.5, P < .01). Total, free testosterone and free androgen index were higher in men (11.5, 36.6 and 40.6 fold, respectively, P < .01). AMPKα phosphorylation was 2.2-fold higher in men compared to women (P < .01). Total Ser(221)ACCβ and Thr(286)CaMKII fractional phosphorylation tended to be higher in men (P = .1). PGC1-α and SIRT1 total protein expression was similar in men and women, whereas CnA tended to be higher in men (P = .1). Basal AMPKα phosphorylation was linearly related to the percentage of MHC I in men (r = 0.56; P < .01), but not in women. No association was observed between anaerobic performance and basal phosphorylations in men and women, analysed separately., Conclusion: In summary, skeletal muscle basal AMPKα phosphorylation is higher in men compared to women, with no apparent effect on anaerobic performance.

Intense exercise training is a powerful stimulus that activates mitochondrial biogenesis pathways and thus increases mitochondrial density and oxidative capacity. Moderate levels of reactive oxygen species (ROS) during exercise are considered vital in the adaptive response, but high ROS production is a serious threat to cellular homeostasis. Although biochemical markers of the transition from adaptive to maladaptive ROS stress are lacking, it is likely mediated by redox sensitive enzymes involved in oxidative metabolism. One potential enzyme mediating such redox sensitivity is the citric acid cycle enzyme aconitase. In this study, we examined biopsy specimens of vastus lateralis and triceps brachii in healthy volunteers, together with primary human myotubes. An intense exercise regimen inactivated aconitase by 55-72%, resulting in inhibition of mitochondrial respiration by 50-65%. In the vastus, the mitochondrial dysfunction was compensated for by a 15-72% increase in mitochondrial proteins, whereas H2O2 emission was unchanged. In parallel with the inactivation of aconitase, the intermediary metabolite citrate accumulated and played an integral part in cellular protection against oxidative stress. In contrast, the triceps failed to increase mitochondrial density, and citrate did not accumulate. Instead, mitochondrial H2O2 emission was decreased to 40% of the pretraining levels, together with a 6-fold increase in protein abundance of catalase. In this study, a novel mitochondrial stress response was highlighted where accumulation of citrate acted to preserve the redox status of the cell during periods of intense exercise., (© FASEB.)

In hypoxia aerobic exercise performance of high-altitude natives is suggested to be superior to that of lowlanders; i.e., for a given altitude natives are reported to have higher maximal oxygen uptake (VO2max). The likely basis for this is a higher pulmonary diffusion capacity, which in turn ensures higher arterial O2 saturation (SaO2) and therefore also potentially a higher delivery of O2 to the exercising muscles. This review focuses on O2 transport in high-altitude Aymara. We have quantified femoral artery O2 delivery, arterial O2 extraction and calculated leg VO2 in Aymara, and compared their values with that of acclimatizing Danish lowlanders. All subjects were studied at 4100 m. At maximal exercise SaO2 dropped tremendously in the lowlanders, but did not change in the Aymara. Therefore arterial O2 content was also higher in the Aymara. At maximal exercise however, fractional O2 extraction was lower in the Aymara, and the a-vO2 difference was similar in both populations. The lower extraction levels in the Aymara were associated with lower muscle O2 conductance (a measure of muscle diffusion capacity). At any given submaximal exercise intensity, leg VO2 was always of similar magnitude in both groups, but at maximal exercise the lowlanders had higher leg blood flow, and hence also higher maximum leg VO2. With the induction of acute normoxia fractional arterial O2 extraction fell in the highlanders, but remained unchanged in the lowlanders. Hence high-altitude natives seem to be more diffusion limited at the muscle level as compared to lowlanders. In conclusion Aymara preserve very high SaO2 during hypoxic exercise (likely due to a higher lung diffusion capacity), but the effect on VO2max is reduced by a lower ability to extract O2 at the muscle level.

In the oxygen (O2) cascade downstream steps can never achieve higher flows of O2 than the preceding ones. At the lung the transfer of O2 is determined by the O2 gradient between the alveolar space and the lung capillaries and the O2 diffusing capacity (DLO2). While DLO2 may be increased several times during exercise by recruiting more lung capillaries and by increasing the oxygen carrying capacity of blood due to higher peripheral extraction of O2, the capacity to enhance the alveolocapillary PO2 gradient is more limited. The transfer of oxygen from the alveolar space to the hemoglobin (Hb) must overcome first the resistance offered by the alveolocapillary membrane (1/DM) and the capillary blood (1/θVc). The fractional contribution of each of these two components to DLO2 remains unknown. During exercise these resistances are reduced by the recruitment of lung capillaries. The factors that reduce the slope of the oxygen dissociation curve of the Hb (ODC) (i.e., lactic acidosis and hyperthermia) increase 1/θVc contributing to limit DLO2. These effects are accentuated in hypoxia. Reducing the size of the active muscle mass improves pulmonary gas exchange during exercise and reduces the rightward shift of the ODC. The flow of oxygen from the muscle capillaries to the mitochondria is pressumably limited by muscle O2 conductance (DmcO2) (an estimation of muscle oxygen diffusing capacity). However, during maximal whole body exercise in normoxia, a higher flow of O2 is achieved at the same pressure gradients after increasing blood [Hb], implying that in healthy humans exercising in normoxia there is a functional reserve in DmcO2. This conclusion is supported by the fact that during small muscle exercise in chronic hypoxia, peak exercise DmcO2 is similar to that observed during exercise in normoxia despite a markedly lower O2 pressure gradient driving diffusion.

Purpose: The aim of this study was to determine if the expression of the mitochondrial biogenesis-regulating proteins SIRT1, SIRT3 and PGC-1alpha in human skeletal muscle is influenced by adiposity., Method: Twenty-nine male subjects were recruited into three groups: control (n = 10), obese (n = 10) and post-obese (n = 9). Intentionally, groups were matched by age, aerobic capacity and in addition the control and post-obese groups also by BMI. Muscle biopsies were obtained from the m. deltoid and vastus lateralis. PGC-1alpha, SIRT1 and SIRT3 protein expression was analyzed by Western blot., Result: PGC-1alpha, SIRT1 and SIRT3 protein expression was similar regardless of the level of adiposity. Only a main effect of group on SIRT1 protein showed a trend toward higher expression in post-obese than control and obese (P = 0.09). Despite similar muscle fiber-type composition (previously reported), PGC-1alpha, SIRT1 and SIRT3 protein expression was higher in leg compared to arm muscle in all groups (P < 0.05)., Conclusion: This study shows that PGC-1alpha, SIRT1 and SIRT3 protein expression in basal conditions was not altered in humans with different levels of adiposity but similar aerobic capacity. The expression of PGC-1alpha, SIRT1 and SIRT3 was higher in vastus lateralis than in deltoid muscle, indicating that local rather than systemic factors prevail in regulating the level of expression of these proteins.

Introduction: the human androgen receptor (AR) gene possesses two trinucleotide polymorphic repeats, (CAG and GGN) that affect the amount of AR protein translated. In this study, we genotyped these polymorphic tracts in a representative sample of Caucasian children (Tanner ≤ 5), 152 boys (11.5 } 2.6 yrs) and 116 girls (10.1 } 3.2 yrs) from Spain and investigated their association with bone mass., Methods: the length of CAG and GGN repeats was determined by PCR and fragment analysis. Body composition was assessed by dual energy x-ray absorptiometry (DXA). Individuals were grouped as CAG short (CAGS) if harboring repeat lengths of ≤ 21 and CAG long (CAGL) if CAG > 21. Moreover, subjects were grouped as GGN short (GGNS) if harboring repeat lengths of ≤ 23 and GGN long (GGNL) if GGN > 23., Results: in boys, significant differences in height, body mass, whole body bone mineral density (BMD) and content (BMC), upper extremities BMC, lower extremities BMC, femoral neck BMD, Ward's triangle BMC and BMD and lumbar spine BMD were observed between CAGS and CAGL groups (P < 0.05). Thus, upper extremities BMD differed between GGNS and GGNL groups. After adjusting for confounding variables, only upper extremities BMD between GGNS and GGNL groups remained significant (P < 0.05). No differences were observed in girls in any measured site in relation to either CAG or GGN polymorphisms length., Conclusions: our results support the hypothesis that longer alleles of the AR CAG and GGN polymorphisms are associated with increased bone mass in prepubertal boys., (Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.)

During evolution, mitochondrial DNA haplogroups of arctic populations may have been selected for lower coupling of mitochondrial respiration to ATP production in favor of higher heat production. We show that mitochondrial coupling in skeletal muscle of traditional and westernized Inuit habituating northern Greenland is identical to Danes of western Europe haplogroups. Biochemical coupling efficiency was preserved across variations in diet, muscle fiber type, and uncoupling protein-3 content. Mitochondrial phenotype displayed plasticity in relation to lifestyle and environment. Untrained Inuit and Danes had identical capacities to oxidize fat substrate in arm muscle, which increased in Danes during the 42 days of acclimation to exercise, approaching the higher level of the Inuit hunters. A common pattern emerges of mitochondrial acclimatization and evolutionary adaptation in humans at high latitude and high altitude where economy of locomotion may be optimized by preservation of biochemical coupling efficiency at modest mitochondrial density, when submaximum performance is uncoupled from VO2max and maximum capacities of oxidative phosphorylation., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

We recently reported the circulatory and muscle oxidative capacities of the arm after prolonged low-intensity skiing in the arctic (Boushel et al., 2014). In the present study, leg VO2 was measured by the Fick method during leg cycling while muscle mitochondrial capacity was examined on a biopsy of the vastus lateralis in healthy volunteers (7 male, 2 female) before and after 42 days of skiing at 60% HR max. Peak pulmonary VO2 (3.52 ± 0.18 L.min(-1) pre vs 3.52 ± 0.19 post) and VO2 across the leg (2.8 ± 0.4L.min(-1) pre vs 3.0 ± 0.2 post) were unchanged after the ski journey. Peak leg O2 delivery (3.6 ± 0.2 L.min(-1) pre vs 3.8 ± 0.4 post), O2 extraction (82 ± 1% pre vs 83 ± 1 post), and muscle capillaries per mm(2) (576 ± 17 pre vs 612 ± 28 post) were also unchanged; however, leg muscle mitochondrial OXPHOS capacity was reduced (90 ± 3 pmol.sec(-1) .mg(-1) pre vs 70 ± 2 post, P < 0.05) as was citrate synthase activity (40 ± 3 μmol.min(-1) .g(-1) pre vs 34 ± 3 vs P < 0.05). These findings indicate that peak muscle VO2 can be sustained with a substantial reduction in mitochondrial OXPHOS capacity. This is achieved at a similar O2 delivery and a higher relative ADP-stimulated mitochondrial respiration at a higher mitochondrial p50. These findings support the concept that muscle mitochondrial respiration is submaximal at VO2max , and that mitochondrial volume can be downregulated by chronic energy demand., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

In humans, arm exercise is known to elicit larger increases in arterial blood pressure (BP) than leg exercise. However, the precise regulation of regional vascular conductances (VC) for the distribution of cardiac output with exercise intensity remains unknown. Hemodynamic responses were assessed during incremental upright arm cranking (AC) and leg pedalling (LP) to exhaustion (Wmax) in nine males. Systemic VC, peak cardiac output (Qpeak) (indocyanine green) and stroke volume (SV) were 18%, 23%, and 20% lower during AC than LP. The mean BP, the rate-pressure product and the associated myocardial oxygen demand were 22%, 12%, and 14% higher, respectively, during maximal AC than LP. Trunk VC was reduced to similar values at Wmax. At Wmax, muscle mass-normalized VC and fractional O2 extraction were lower in the arm than the leg muscles. However, this was compensated for during AC by raising perfusion pressure to increase O2 delivery, allowing a similar peak VO2 per kg of muscle mass in both extremities. In summary, despite a lower Qpeak during arm cranking the cardiovascular strain is much higher than during leg pedalling. The adjustments of regional conductances during incremental exercise to exhaustion depend mostly on the relative intensity of exercise and are limb-specific., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Age-related decline in cardiac function can be prevented or postponed by lifelong endurance training. However, effects of normal ageing as well as of lifelong endurance exercise on longitudinal and radial contribution to stroke volume are unknown. The aim of this study was to determine resting longitudinal and radial pumping in elderly athletes, sedentary elderly and young sedentary subjects. Furthermore, we aimed to investigate determinants of maximal cardiac output in elderly. Eight elderly athletes (63 ± 4 years), seven elderly sedentary (66 ± 4 years) and ten young sedentary subjects (29 ± 4 years) underwent cardiac magnetic resonance imaging. All subjects underwent maximal exercise testing and for elderly subjects maximal cardiac output during cycling was determined using a dye dilution technique. Longitudinal and radial contribution to stroke volume did not differ between groups (longitudinal left ventricle (LV) 52-65%, P = 0.12, right ventricle (RV) 77-87%, P = 0.16, radial 7.9-8.6%, P = 1.0). Left ventricular atrioventricular plane displacement (LVAVPD) was higher in elderly athletes and young sedentary compared with elderly sedentary subjects (14 ± 3, 15 ± 2 and 11 ± 1 mm, respectively, P < 0.05). There was no difference between groups for RVAVPD (P = 0.2). LVAVPD was an independent predictor of maximal cardiac output (R(2) = 0.61, P < 0.01, β = 0.78). Longitudinal and radial contributions to stroke volume did not differ between groups. However, how longitudinal pumping was achieved differed; elderly athletes and young sedentary subjects showed similar AVPD whereas this was significantly lower in elderly sedentary subjects. Elderly sedentary subjects achieved longitudinal pumping through increased short-axis area of the ventricle. Large AVPD was a determinant of maximal cardiac output and exercise capacity., (© 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.)

It is investigated if recombinant human erythropoietin (rHuEPO) treatment for 15 weeks (n = 8) reduces extracellular accumulation of metabolic stress markers such as lactate, H(+) , and K(+) during incremental exhaustive exercise. After rHuEPO treatment, normalization of blood volume and composition by hemodilution preceded an additional incremental test. Group averages were calculated for an exercise intensity ∼80% of pre-rHuEPO peak power output. After rHuEPO treatment, leg lactate release to the plasma compartment was similar to before (4.3 ± 1.6 vs 3.9 ± 2.5 mmol/min) and remained similar after hemodilution. Venous lactate concentration was higher (P < 0.05) after rHuEPO treatment (7.1 ± 1.6 vs 5.2 ± 2.1 mM). Leg H(+) release to the plasma compartment after rHuEPO was similar to before (19.6 ± 5.4 vs 17.6 ± 6.0 mmol/min) and remained similar after hemodilution. Nevertheless, venous pH was lower (P < 0.05) after rHuEPO treatment (7.18 ± 0.04 vs 7.22 ± 0.05). Leg K(+) release to the plasma compartment after rHuEPO treatment was similar to before (0.8 ± 0.5 vs 0.7 ± 0.7 mmol/min) and remained similar after hemodilution. Additionally, venous K(+) concentrations were similar after vs before rHuEPO (5.3 ± 0.3 vs 5.1 ± 0.4 mM). In conclusion, rHuEPO does not reduce plasma accumulation of lactate, H(+) , and K(+) at work rates corresponding to ∼80% of peak power output., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

To determine the contribution of convective and diffusive limitations to V̇(O2peak) during exercise in humans, oxygen transport and haemodynamics were measured in 11 men (22 ± 2 years) during incremental (IE) and 30 s all-out cycling sprints (Wingate test, WgT), in normoxia (Nx, P(IO2): 143 mmHg) and hypoxia (Hyp, P(IO2): 73 mmHg). Carboxyhaemoglobin (COHb) was increased to 6-7% before both WgTs to left-shift the oxyhaemoglobin dissociation curve. Leg V̇(O2) was measured by the Fick method and leg blood flow (BF) with thermodilution, and muscle O2 diffusing capacity (D(MO2)) was calculated. In the WgT mean power output, leg BF, leg O2 delivery and leg V̇(O2) were 7, 5, 28 and 23% lower in Hyp than Nx (P < 0.05); however, peak WgT D(MO2) was higher in Hyp (51.5 ± 9.7) than Nx (20.5 ± 3.0 ml min(-1) mmHg(-1), P < 0.05). Despite a similar P(aO2) (33.3 ± 2.4 and 34.1 ± 3.3 mmHg), mean capillary P(O2) (16.7 ± 1.2 and 17.1 ± 1.6 mmHg), and peak perfusion during IE and WgT in Hyp, D(MO2) and leg V̇(O2) were 12 and 14% higher, respectively, during WgT than IE in Hyp (both P < 0.05). D(MO2) was insensitive to COHb (COHb: 0.7 vs. 7%, in IE Hyp and WgT Hyp). At exhaustion, the Y equilibration index was well above 1.0 in both conditions, reflecting greater convective than diffusive limitation to the O2 transfer in both Nx and Hyp. In conclusion, muscle V̇(O2) during sprint exercise is not limited by O2 delivery, O2 offloading from haemoglobin or structure-dependent diffusion constraints in the skeletal muscle. These findings reveal a remarkable functional reserve in muscle O2 diffusing capacity., (© 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.)

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., (© 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.)

Negative arterial to end-tidal pco2 differences ((a-ET)pco2) have been reported in normoxia. To determine the influence of blood temperature on (a-ET)pco2, 11 volunteers (21 ± 2 years) performed incremental exercise to exhaustion in normoxia (Nx, Pio2: 143 mmHg) and hypoxia (Hyp, Pio2: 73 mmHg), while arterial blood gases and temperature (ABT) were simultaneously measured together with end-tidal pco2 (PE tco2). After accounting for blood temperature, the (a-ET) pco2 was reduced (in absolute values) from -4.2 ± 1.6 to -1.1 ± 1.5 mmHg in normoxia and from -1.7 ± 1.6 to 0.9 ± 0.9 mmHg in hypoxia (both P < 0.05). The temperature corrected (a-ET)pco2 was linearly related with absolute and relative exercise intensity, VO2, VCO2, and respiratory rate (RR) in normoxia and hypoxia (R(2): 0.52-0.59). Exercise CO2 production and PE tco2 values were lower in hypoxia than normoxia, likely explaining the greater (less negative) (a-ET)pco2 difference in hypoxia than normoxia (P < 0.05). At near-maximal exercise intensity the (a-ET)pco2 lies close to 0 mmHg, that is, the mean Paco2 and the mean PE tco2 are similar. The mean exercise (a-ET)pco2 difference is closely related to the mean A-aDO2 difference (r = 0.90, P < 0.001), as would be expected if similar mechanisms perturb the gas exchange of O2 and CO2 during exercise. In summary, most of the negative (a-ET)pco2 values observed in previous studies are due to lack of correction of Paco2 for blood temperature. The absolute magnitude of the (a-ET)pco2 difference is lower during exercise in hypoxia than normoxia., (© 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.)

New Findings: What is the central question of this study? Temperature-sensitive mechanisms are thought to contribute to blood-flow regulation, but the relationship between exercising and non-exercising limb perfusion and blood temperature is not established. What is the main finding and its importance? The close coupling among perfusion, blood temperature and aerobic metabolism in exercising and non-exercising extremities across different exercise modalities and activity levels and the tight association between limb vasodilatation and increases in plasma ATP suggest that both temperature- and metabolism-sensitive mechanisms are important for the control of human limb perfusion, possibly by activating ATP release from the erythrocytes. Temperature-sensitive mechanisms may contribute to blood-flow regulation, but the influence of temperature on perfusion to exercising and non-exercising human limbs is not established. Blood temperature (TB ), blood flow and oxygen uptake (V̇O2) in the legs and arms were measured in 16 healthy humans during 90 min of leg and arm exercise and during exhaustive incremental leg or arm exercise. During prolonged exercise, leg blood flow (LBF) was fourfold higher than arm blood flow (ABF) in association with higher TB and limb V̇O2. Leg and arm vascular conductance during exercise compared with rest was related closely to TB (r(2) = 0.91; P < 0.05), plasma ATP (r(2) = 0.94; P < 0.05) and limb V̇O2 (r(2) = 0.99; P < 0.05). During incremental leg exercise, LBF increased in association with elevations in TB and limb V̇O2, whereas ABF, arm TB and V̇O2 remained largely unchanged. During incremental arm exercise, both ABF and LBF increased in relationship to similar increases in V̇O2. In 12 trained males, increases in femoral TB and LBF during incremental leg exercise were mirrored by similar pulmonary artery TB and cardiac output dynamics, suggesting that processes in active limbs dominate central temperature and perfusion responses. The present data reveal a close coupling among perfusion, TB and aerobic metabolism in exercising and non-exercising extremities and a tight association between limb vasodilatation and increases in plasma ATP. These findings suggest that temperature and V̇O2 contribute to the regulation of limb perfusion through control of intravascular ATP., (© 2015 The Authors Experimental Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

To determine whether a fast reduction in fat mass can be achieved in 4 days by combining caloric restriction (CR: 3.2 kcal/kg body weight per day) with exercise (8-h walking + 45-min arm cranking per day) to induce an energy deficit of ∼5000 kcal/day, 15 overweight men underwent five experimental phases: pretest, exercise + CR for 4 days (WCR), control diet + reduced exercise for 3 days (DIET), and follow-up 4 weeks (POST1) and 1 year later (POST2). During WCR, the diet consisted solely of whey protein (n = 8) or sucrose (n = 7) (0.8 g/kg body weight per day). After WCR, DIET, POST1, and POST2, fat mass was reduced by a mean of 2.1, 2.8, 3.8, and 1.9 kg (P < 0.05), with two thirds of this loss from the trunk; and lean mass by 2.8, 1.0, 0.5, and 0.4 kg, respectively. After WCR, serum glucose, insulin, homeostatic model assessment, total and low-density lipoprotein cholesterol and triglycerides were reduced, and free fatty acid and cortisol increased. Serum leptin was reduced by 64%, 50%, and 33% following WCR, DIET, and POST1, respectively (P < 0.05). The effects were similar in both groups. In conclusion, a clinically relevant reduction in fat mass can be achieved in overweight men in just 4 days by combining prolonged exercise with CR., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The accuracy and reproducibility of transpulmonary thermodilution (TPTd) to assess cardiac output (Q̇) in exercising men was determined using indocyanine green (ICG) dilution as a reference method. TPTd has been utilized for the assessment of Q̇ and preload indexes of global end-diastolic volume and intrathoracic blood volume, as well as extravascular lung water (EVLW) in resting humans. It remains unknown if this technique is also accurate and reproducible during exercise. Sixteen healthy men underwent catheterization of the right femoral vein (for iced saline injection), an antecubital vein (ICG injection), and femoral artery (thermistor) to determine their Q̇ by TPTd and ICG concentration during incremental one- and two-legged pedaling on a cycle ergometer and combined arm cranking with leg pedaling to exhaustion. There was a close relationship between TPTd-Q̇ and ICG-Q̇ (r = 0.95, n = 151, standard error of the estimate: 1.452 l/min, P < 0.001; mean difference of 0.06 l/min; limits of agreement -2.98 to 2.86 l/min), and TPTd-Q̇ and ICG-Q̇ increased linearly with oxygen uptake with similar intercepts and slopes. Both methods had mean coefficients of variation close to 5% for Q̇, global end-diastolic volume, and intrathoracic blood volume. The mean coefficient of variation of EVLW, assessed with both indicators (ICG and thermal) was 17% and was sensitive enough to detect a reduction in EVLW of 107 ml when changing from resting supine to upright exercise. In summary, TPTd with bolus injection into the femoral vein is an accurate and reproducible method to assess Q̇ during exercise in humans., (Copyright © 2015 the American Physiological Society.)

The aim of this study was to determine the influence of severe acute hypoxia on muscle activation during whole body dynamic exercise. Eleven young men performed four incremental cycle ergometer tests to exhaustion breathing normoxic (FIO2=0.21, two tests) or hypoxic gas (FIO2=0.108, two tests). Surface electromyography (EMG) activities of rectus femoris (RF), vastus medialis (VL), vastus lateralis (VL), and biceps femoris (BF) were recorded. The two normoxic and the two hypoxic tests were averaged to reduce EMG variability. Peak VO2 was 34% lower in hypoxia than in normoxia (p<0.05). The EMG root mean square (RMS) increased with exercise intensity in all muscles (p<0.05), with greater effect in hypoxia than in normoxia in the RF and VM (p<0.05), and a similar trend in VL (p=0.10). At the same relative intensity, the RMS was greater in normoxia than in hypoxia in RF, VL, and BF (p<0.05), with a similar trend in VM (p=0.08). Median frequency increased with exercise intensity (p<0.05), and was higher in hypoxia than in normoxia in VL (p<0.05). Muscle contraction burst duration increased with exercise intensity in VM and VL (p<0.05), without clear effects of FIO2. No significant FIO2 effects on frequency domain indices were observed when compared at the same relative intensity. In conclusion, muscle activation during whole body exercise increases almost linearly with exercise intensity, following a muscle-specific pattern, which is adjusted depending on the FIO2 and the relative intensity of exercise. Both VL and VM are increasingly involved in power output generation with the increase of intensity and the reduction in FIO2.

To examine whether blood lactate and ammonia concentrations can be used to estimate the functional state of the muscle contractile machinery with regard to muscle lactate and adenosine triphosphate (ATP) levels during leg press exercise. Thirteen men (age, 34 ± 5 years; 1 repetition maximum leg press strength 199 ± 33 kg) performed either 5 sets of 10 repetitions to failure (5×10RF), or 10 sets of 5 repetitions not to failure (10×5RNF) with the same initial load (10RM) and interset rests (2 minutes) on 2 separate sessions in random order. Capillary blood samples were obtained before and during exercise and recovery. Six subjects underwent vastus lateralis muscle biopsies at rest, before the first set and after the final exercise set. The 5×10RF resulted in a significant and marked decrease in power output (37%), muscle ATP content (24%), and high levels of muscle lactate (25.0 ± 8.1 mmol·kg wet weight), blood lactate (10.3 ± 2.6 mmol·L), and blood ammonia (91.6 ± 40.5 μmol·L). During 10×5RNF no or minimal changes were observed. Significant correlations were found between: (a) blood ammonia and muscle ATP (r = -0.75), (b) changes in peak power output and blood ammonia (r = -0.87) and blood lactate (r = -0.84), and (c) blood and muscle lactate (r = 0.90). Blood lactate and ammonia concentrations can be used as extracellular markers for muscle lactate and ATP contents, respectively. The decline in mechanical power output can be used to indirectly estimate blood ammonia and lactate during leg press exercise.

Aims: To determine the role played by adenosine, ATP and chemoreflex activation on the regulation of vascular conductance in chronic hypoxia., Methods: The vascular conductance response to low and high doses of adenosine and ATP was assessed in ten healthy men. Vasodilators were infused into the femoral artery at sea level and then after 8-12 days of residence at 4559 m above sea level. At sea level, the infusions were carried out while the subjects breathed room air, acute hypoxia (FI O2 = 0.11) and hyperoxia (FI O2 = 1); and at altitude (FI O2 = 0.21 and 1). Skeletal muscle P2Y2 receptor protein expression was determined in muscle biopsies after 4 weeks at 3454 m by Western blot., Results: At altitude, mean arterial blood pressure was 13% higher (91 ± 2 vs. 102 ± 3 mmHg, P < 0.05) than at sea level and was unaltered by hyperoxic breathing. Baseline leg vascular conductance was 25% lower at altitude than at sea level (P < 0.05). At altitude, the high doses of adenosine and ATP reduced mean arterial blood pressure by 9-12%, independently of FI O2 . The change in vascular conductance in response to ATP was lower at altitude than at sea level by 24 and 38%, during the low and high ATP doses respectively (P < 0.05), and by 22% during the infusion with high adenosine doses. Hyperoxic breathing did not modify the response to vasodilators at sea level or at altitude. P2Y2 receptor expression remained unchanged with altitude residence., Conclusions: Short-term residence at altitude increases arterial blood pressure and reduces the vasodilatory responses to adenosine and ATP., (© 2014 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.)

Aim: It is an ongoing discussion the extent to which oxygen delivery and oxygen extraction contribute to an increased muscle oxygen uptake during dynamic exercise. It has been proposed that local muscle factors including the capillary bed and mitochondrial oxidative capacity play a large role in prolonged low-intensity training of a small muscle group when the cardiac output capacity is not directly limiting. The purpose of this study was to investigate the relative roles of circulatory and muscle metabolic mechanisms by which prolonged low-intensity exercise training alters regional muscle VO2 ., Methods: In nine healthy volunteers (seven males, two females), haemodynamic and metabolic responses to incremental arm cycling were measured by the Fick method and biopsy of the deltoid and triceps muscles before and after 42 days of skiing for 6 h day(-1) at 60% max heart rate., Results: Peak pulmonary VO2 during arm crank was unchanged after training (2.38 ± 0.19 vs. 2.18 ± 0.2 L min(-1) pre-training) yet arm VO2 (1.04 ± 0.08 vs. 0.83 ± 0.1 L min(1) , P < 0.05) and power output (137 ± 9 vs. 114 ± 10 Watts) were increased along with a higher arm blood flow (7.9 ± 0.5 vs. 6.8 ± 0.6 L min(-1) , P < 0.05) and expanded muscle capillary volume (76 ± 7 vs. 62 ± 4 mL, P < 0.05). Muscle O2 diffusion capacity (16.2 ± 1 vs. 12.5 ± 0.9 mL min(-1) mHg(-1) , P < 0.05) and O2 extraction (68 ± 1 vs. 62 ± 1%, P < 0.05) were enhanced at a similar mean capillary transit time (569 ± 43 vs. 564 ± 31 ms) and P50 (35.8 ± 0.7 vs. 35 ± 0.8), whereas mitochondrial O2 flux capacity was unchanged (147 ± 6 mL kg min(-1) vs. 146 ± 8 mL kg min(-1) )., Conclusion: The mechanisms underlying the increase in peak arm VO2 with prolonged low-intensity training in previously untrained subjects are an increased convective O2 delivery specifically to the muscles of the arm combined with a larger capillary-muscle surface area that enhance diffusional O2 conductance, with no apparent role of mitochondrial respiratory capacity., (© 2014 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.)

Aim: Age associated fat mass accumulation could be because of dysregulation of leptin signalling in skeletal muscle. Thus, we investigated total protein expression and phosphorylation levels of the long isoform of the leptin receptor (OB-Rb), and leptin signalling through janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3), insulin receptor substrate 1 (IRS-1), AMP-activated protein kinase (AMPK) and acetyl-coenzyme A carboxylase (ACC), combined with the leptin signalling inhibitors suppressor of cytokine signalling 3 (SOCS3) and protein tyrosine phosphatase 1B (PTP1B) in human skeletal muscle of different age., Methods: Vastus lateralis muscle biopsies were obtained from 39 men matched for BMI < 30 kg m(-2) and separated into three groups: 13 young (Y, 24 ± 4 years); 14 middle aged (MA, 44 ± 5 years) and 12 aged (A, 58 ± 8 years) subjects., Results: Whole body fat percentage and plasma leptin were higher (P < 0.05), whereas lean mass, plasma free testosterone and total testosterone were lower (P < 0.05) in A compared to Y. Skeletal muscle OB-Rb (170 KDa) protein expression and pTyr(1141) -OB-R170 were comparable between groups, whereas pTyr(985) -OB-R170 was lower in A compared to Y (P < 0.05). pSTAT3 levels tended (P = 0.09) to be lower (50%) in A compared to Y. In A, muscle PTP1B was greater and IRS-1 lower than Y and MA respectively (P < 0.05). PTyr(612) -IRS-1 tended to be lower in A than in Y (P = 0.09). Suppressor of cytokine signalling 3 (SOCS3) protein expression, pJAK2, pSer(1101) -IRS-1, pAMPKα and pACCβ were similar between groups., Conclusion: Age is associated with dysregulation of the leptin signalling and increased PTP1B protein expression in skeletal muscle., (© 2014 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.)

Background: The aim was to develop a unipedal stance test for the assessment of balance using a force platform., Methods: A single-leg balance test was conducted in 23 students (mean ± SD) age: 23 ± 3 years) in a standard position limiting the movement of the arms and non-supporting leg. Six attempts, with both the jumping (JL) and the contralateral leg (CL), were performed under 3 conditions: 1) eyes opened; 2) eyes closed; 3) eyes opened and executing a precision task. The same protocol was repeated two-week apart., Results: The mean and the best result of the six attempts performed each day were taken as representative of balance. The speed of the centre of pressure (CP-Speed) showed excellent reliability for the "best result" analysis in all tests (ICCs 0.87-0.97), except in the test with the eyes closed performed on the CL (ICC<0.4). The CP-Speed had better reliability with the "best result" than with the "mean result" analysis (P<0.05), whilst no significant differences were observed between the JL and the CL (P=0.71 and P=0.96 for mean and best results analysis, respectively). A lower dispersion in the Bland and Altman graph was observed with the eyes opened than closed, and the dynamic test., Conclusion: The single-leg stance balance test proposed is a reliable method to assess balance, especially when performed in a static position, with the eyes opened and using the best result of six attempts as reference, independently of the stance leg.

Purpose: This study aimed at determining the effects of bed rest on the skeletal muscle leptin signaling system., Methods: Deltoid and vastus lateralis muscle biopsies and blood samples were obtained from 12 healthy young men (mean ± SD, BMI 22.8 ± 2.7 kg/m(2)) before and after 7 days of bed rest. Leptin receptor isoforms (OB-Rs), suppressor of cytokine signaling 3 (SOCS3) and protein tyrosine phosphatase 1B (PTP1B) protein expression and signal transducer and activator of transcription 3 (STAT3) phosphorylation were analyzed by Western blot., Results: After bed rest basal insulin concentration was increased by 53% (P < 0.05), the homeostasis model assessment (HOMA) by 40% (P < 0.05), and serum leptin concentration by 35% (P < 0.05) with no changes in body fat mass. Although the soluble isoform of the leptin receptor (s-OBR) remained unchanged, the molar excess of leptin over sOB-R was increased by 1.4-fold after bed rest (P < 0.05). OB-Rs and SOCS3 protein expression, and STAT3 phosphorylation level remained unaffected in deltoid and vastus lateralis by bed rest, as PTP1B in the deltoid. PTP1B was increased by 90% with bed rest in the vastus lateralis (P < 0.05). There was a linear relationship between the increase in vastus lateralis PTP1B and the increase in both basal insulin concentrations (r = 0.66, P < 0.05) and HOMA (r = 0.68, P < 0.05) with bed rest., Conclusions: One week of bed rest is associated with increased leptin levels without augmenting STAT3 phosphorylation indicating some degree of leptin resistance in skeletal muscle, which can be explained, at least in part, by an elevation of PTP1B protein content in the vastus lateralis muscle.

Sprint exercise ability has been critical for survival. The remarkably high-power output levels attained during sprint exercise are achieved through strong activation of anaerobic, and to a lesser extent, aerobic energy supplying metabolic reactions, which generate reactive oxygen and nitrogen species (RONS). Sprint exercise may cause oxidative stress leading to muscle damage, particularly when performed in severe acute hypoxia. However, with training oxidative stress is reduced. Paradoxically, total plasma antioxidant capacity increases during the subsequent 2 h after a short sprint due to the increase in plasma urate concentration. The RONS produced during and immediately after sprint exercise play a capital role in signaling the adaptive response to sprint. Antioxidant supplementation blunts the normal AMPKα and CaMKII phosphorylation in response to sprint exercise. However, under conditions of increased glycolytic energy turnover and muscle acidification, as during sprint exercise in severe acute hypoxia, AMPKα phosphorylation is also blunted. This indicates that an optimal level of RONS-mediated stimulation is required for the normal signaling response to sprint exercise. Although RONS are implicated in fatigue, most studies convey that antioxidants do not enhance sprint performance in humans. Although currently controversial, it has been reported that antioxidant ingestion during training may jeopardize some of the beneficial adaptations to sprint training.

Aim: This study aims to review the main methods used to improve vertical jump performance (VJP)., Methods: Although many training routines have been proposed, these can be grouped into four main categories: plyometric training (PT), weight training (WT), whole body vibration training (VT) and electromyostimulation training (ET). PT enhances muscular force, the rate of force development (RFD), muscular power, muscle contraction velocity, cross-sectional area (CSA), muscle stiffness allowing greater storage and release of elastic energy. WT improve muscular force, velocity, power output, and RFD during jumping on a force plate, muscle hypertrophy and neural adaptations. One of the most effective methods to improve VJP is the combination of PT with WT, which takes advantage of the enhancement of maximal dynamic force through WT and the positive effects of PT on speed and force of muscle contraction through its specific effect on type II fibers., Results: Some authors have found an increase in VJP with the use of VT while other did not see such an effect. However, it remains unknown by which mechanisms VT could enhance VJP. ET has been shown to elicit muscle hypertrophy. The VJP may be improved when ET is applied concomitantly with PT or practice of sports., Conclusion: In summary, scientific evidence suggests that the best way to improve VJP is through the combination of PT with WT. Further research is needed to establish if better results are possible by more complex strategies.