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Heat acclimatization may help personnel who travel to areas with a hot climate (WBGT > 27⯰C), making them operationally more efficient and performant through improvements in physiological and psychological parameters. Their work-related physical activities may aid active heat acclimatization. However, it is unknown whether adding physical training to improve adaptation is effective, particularly if there is sufficient time for full acclimatization, classically reached after 15 days. Thirty French soldiers (Training group, T) performed a progressive and moderate (from three to five 8-min running sets at 50-60% of their speed at VO2max with 4-min periods of active recovery in between) aerobic training program upon arriving at their base in United Arab Emirates (~40⯰C and 20% RH). A control group (30 soldiers; No Training, NT) continued to perform only their usual outdoor military activities (~5â¯h d-1). A field heat stress test (HST: three 8-min running sets at 50% of the speed at VO2max) was performed before (D0), during (D10), and after (D15) the heat acclimatization period to assess physiological and psychological changes. An 8-km trial in battledress was then performed at D17. Although physiological modifications were mostly similar (pâ¯<â¯0.001 for all) for both groups (rectal temperature at the end of the HST: -0.58⯱â¯0.51 vs -0.53⯱â¯0.40⯰C, HR at the end of the HST: -21⯱â¯12 vs -19⯱â¯9 bpm, and sweat osmolality: -47⯱â¯30 vs -26⯱â¯32 mOsmol.l-1 between D15 and D0 for T and NT groups, respectively), thermal discomfort (-31⯱â¯4 vs -11⯱â¯5â¯mm between D15 and D0, pâ¯=â¯0.001) and rates of perceived exertion (-3.0⯱â¯0.4 vs -1.4⯱â¯0.3 D15 and D0, pâ¯=â¯0.001) were much lower in the T than NT group during the HST. HST-induced modifications in facial temperature only decreased in the T group (-1.08⯱â¯0.28 between D15 and D0, pâ¯<â¯0.001). Moreover, there was a difference in perceived thermal discomfort during the 8-km trial (40⯱â¯20 vs 55⯱â¯22â¯mm for the T and NT groups, respectively, pâ¯=â¯0.010). Thus, a 15-day, low-volume training regimen during a mission in a hot and dry environment has a modest impact on physiological adaptation but strongly decreases the perceived strain of exertion and climate potentially via greater reductions in facial temperature, even during a classical operational physical task in a military context.
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Aclimatação , Exercício Físico , Resposta ao Choque Térmico , Sudorese , Adaptação Psicológica , Adulto , Temperatura Corporal , Clima , Temperatura Alta , Humanos , Militares , Corrida , Adulto JovemRESUMO
Over the last several years, converging lines of evidence have indicated that miR-206 plays a pivotal role in promoting muscle differentiation and regeneration, thereby potentially impacting positively on the progression of neuromuscular disorders, including Duchenne muscular dystrophy (DMD). Despite several studies showing the regulatory function of miR-206 on target mRNAs in skeletal muscle cells, the effects of overexpression of miR-206 in dystrophic muscles remain to be established. Here, we found that miR-206 overexpression in mdx mouse muscles simultaneously targets multiple mRNAs and proteins implicated in satellite cell differentiation, muscle regeneration, and at the neuromuscular junction. Overexpression of miR-206 also increased the levels of several muscle-specific mRNAs/proteins, while enhancing utrophin A expression at the sarcolemma. Finally, we also observed that the increased expression of miR-206 in dystrophin-deficient mouse muscle decreased the production of proinflammatory cytokines and infiltration of macrophages. Taken together, our results show that miR-206 acts as a pleiotropic regulator that targets multiple key mRNAs and proteins expected to provide beneficial adaptations in dystrophic muscle, thus highlighting its therapeutic potential for DMD.
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Adaptação Fisiológica , Citocinas/metabolismo , Macrófagos/metabolismo , Proteínas Musculares/metabolismo , Músculo Esquelético/metabolismo , Distrofia Muscular de Duchenne/metabolismo , Animais , Regulação da Expressão Gênica , Macrófagos/patologia , Masculino , Camundongos , Músculo Esquelético/patologia , Distrofia Muscular de Duchenne/patologia , Ligação Proteica , Distribuição TecidualRESUMO
Skeletal muscle damage is an often-occurring event. Diagnosis using the classic blood marker creatine kinase sometimes yields unsatisfactory results due to great interindividual variability. Therefore, the identification of reliable biomarkers is important. Our aim was to detect and characterize circulating miRNAs in plasma in response to acute notexin-induced muscle damage in rats. Real-time quantitative RT-PCR profiling led to the identification of miRNAs that were highly increased in plasma in response to notexin injection into several muscles, namely miR-1-3p, -133a-3p, -133b-3p, -206-3p, -208b-3p, and -499-5p, as well as miR-378a-3p and miR-434-3p. Peak values of miRNAs appeared 12 hours after injury, and were contained both in the vesicular and nonvesicular fractions of plasma. Receiver operating characteristic curve analysis showed that circulating miRNAs could accurately discriminate between damaged and nondamaged tissues. Furthermore, we tested the robustness of expression profiles in slow- and fast-type fibers. Upon inducing damage in slow- or fast-type muscle, we found that the damaged-muscle phenotype had a very limited impact on the miRNA response. Similarly, the circulating miRNAs selected were not affected by hemolysis or platelets, two pre-analytical factors known to affect plasma miRNA profiles. Taken together, our results show that circulating muscle-specific miRNAs, miR-378a-3p and miR-434-3p, are robust and promising biomarkers of acute muscle damage in rats.
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MicroRNAs/metabolismo , Doenças Musculares/diagnóstico , Animais , Biomarcadores/metabolismo , Venenos Elapídicos/toxicidade , Feminino , Masculino , Músculo Esquelético/efeitos dos fármacos , Doenças Musculares/induzido quimicamente , Neurotoxinas/toxicidade , Ratos WistarRESUMO
INTRODUCTION: As skeletal muscle mass recovery after extensive injury is improved by contractile activity, we explored whether concomitant exercise accelerates recovery of the contractile and metabolic phenotypes after muscle injury. METHODS: After notexin-induced degeneration of a soleus muscle, Wistar rats were assigned to active (running exercise) or sedentary groups. Myosin heavy chains (MHC), metabolic enzymes, and calcineurin were studied during muscle regeneration at different time points. RESULTS: The mature MHC profile recovered earlier in active rats (21 days after injury) than in sedentary rats (42 days). Calcineurin was higher in the active degenerated than in the sedentary degenerated muscles at day 14. Citrate synthase and total lactate dehydrogenase (LDH) activity decreased after injury and were similarly recovered in both active and sedentary groups at 14 or 42 days, respectively. H-LDH isozyme activity recovered earlier in the active rats. CONCLUSIONS: Exercise improved recovery of the slow/oxidative phenotype after soleus muscle injury. Muscle Nerve 55: 91-100, 2017.
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Fibras Musculares de Contração Lenta/fisiologia , Doenças Musculares/fisiopatologia , Doenças Musculares/reabilitação , Condicionamento Físico Animal/métodos , Regeneração/fisiologia , Animais , Calcineurina/metabolismo , Citrato (si)-Sintase/metabolismo , Modelos Animais de Doenças , Venenos Elapídicos/toxicidade , Teste de Esforço , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Peptídeos e Proteínas de Sinalização Intracelular , Isoenzimas/genética , Isoenzimas/metabolismo , L-Lactato Desidrogenase/genética , L-Lactato Desidrogenase/metabolismo , Lactato Desidrogenase 5 , Doenças Musculares/induzido quimicamente , Cadeias Pesadas de Miosina/genética , Cadeias Pesadas de Miosina/metabolismo , Tamanho do Órgão/efeitos dos fármacos , Oxirredução/efeitos dos fármacos , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Regeneração/efeitos dos fármacos , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismoRESUMO
Aircraft pilots face a high mental workload (MW) under environmental constraints induced by high altitude and sometimes sleep restriction (SR). Our aim was to assess the combined effects of hypoxia and sleep restriction on cognitive and physiological responses to different MW levels using the Multi-Attribute Test Battery (MATB)-II with an additional auditory Oddball-like task. Seventeen healthy subjects were subjected in random order to three 12-min periods of increased MW level (low, medium, and high): sleep restriction (SR, <3 h of total sleep time (TST)) vs. habitual sleep (HS, >6 h TST), hypoxia (HY, 2 h, FIO2 = 13.6%, ~3500 m vs. normoxia, NO, FIO2 = 21%). Following each MW level, participants completed the NASA-TLX subjective MW scale. Increasing MW decreases performance on the MATB-II Tracking task (p = 0.001, MW difficulty main effect) and increases NASA-TLX (p = 0.001). In the combined HY/SR condition, MATB-II performance was lower, and the NASA-TLX score was higher compared with the NO/HS condition, while no effect of hypoxia alone was observed. In the accuracy of the auditory task, there is a significant interaction between hypoxia and MW difficulty (F(2-176) = 3.14, p = 0.04), with lower values at high MW under hypoxic conditions. Breathing rate, pupil size, and amplitude of pupil dilation response (PDR) to auditory stimuli are associated with increased MW. These parameters are the best predictors of increased MW, independently of physiological constraints. Adding ECG, SpO2, or electrodermal conductance does not improve model performance. In conclusion, hypoxia and sleep restriction have an additive effect on MW. Physiological and electrophysiological responses must be taken into account when designing a MW predictive model and cross-validation.
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INTRODUCTION: Exposure to moderate levels of simulated hypoxia has subtle cognitive effects relative to ground level, in healthy individuals. However, there are few data on the cognitive consequences of the combination of hypoxia and partial sleep deprivation, which is a classic military or civilian operational context. In this study, we tested the hypothesis that exposure to moderate hypoxia while sleep-restricted impairs several domains of cognition, and we also assessed physiological parameters and salivary concentrations of cortisol and alpha-amylase. METHOD: Seventeen healthy males completed two sessions of cognitive tests (sustained attention using the PVT psychomotor vigilance task and executive functions using the Go-NoGo inhibition task and N-Back working memory task) after 30 minutes (T+30') and 4 hours (T+240') of exposure in a normobaric hypoxic tent (FIO2â¯=â¯13.6%, ≃ 3,500 m) (HY). This was completed after one night of sleep restriction (3 a.m. to 6 a.m. bedtime, SRHY) and one night of habitual sleep (10 p.m. to 6 a.m. bedtime, HSHY) (with cross-over randomization). The two nights sleep architecture and physiological parameters (oxygen saturation (SpO2) and heart rate (HR) during T+30' and T+240'sessions were analyzed. Salivary cortisol and alpha-amylase (sAA) concentrations were analyzed before hypoxia, after the T+30' and T+240' cognitive sessions, and after leaving the hypoxic tent. RESULTS: Sustained attention (RT and number of lapses in the PVT) and executive functions (Go-NoGo and 1-Back and 2-Back parameters, as inhibition and working memory signatures) were impaired in the SRHY condition compared to HSHY. SpO2 and HR were higher after 4 hours compared with 30 minutes of hypoxia in the HSHY condition, while only HR was statistically higher in the SRHY condition. In SRHY, salivary AA concentration was lower and cortisol was higher than in HSHY. A significant increase in sAA concentration is observed after the cognitive session at 4 hours of hypoxia exposure compared to that at 30 minutes, only in the SRHY condition. There are significant positive correlations between reaction time and the corresponding heart rate (a non-invasive marker of physiological stress) for the executive tasks in the two sleep conditions. This was not observed for salivary levels of sAA and cortisol, respective reliable indicators of the sympathoadrenomedullary system and the hypothalamic-pituitary adrenocortical system. CONCLUSION: Exposure to moderate normobaric hypoxia (≃ 3,500 m / ≃ 11,500 ft simulated) after a single night of 3-hour sleep impairs cognitive performance after 30 minutes and 4 hours of exposure. The key determinants and/or mechanism(s) responsible for cognitive impairment when exposed to moderate hypoxia with sleep restriction, particularly on the executive function, have yet to be elucidated.
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Hypoxia induces a loss of skeletal muscle mass, but the signaling pathways and molecular mechanisms involved remain poorly understood. We hypothesized that hypoxia could impair skeletal muscle hypertrophy induced by functional overload (Ov). To test this hypothesis, plantaris muscles were overloaded during 5, 12, and 56 days in female rats exposed to hypobaric hypoxia (5,500 m), and then, we examined the responses of specific signaling pathways involved in protein synthesis (Akt/mTOR) and breakdown (atrogenes). Hypoxia minimized the Ov-induced hypertrophy at days 5 and 12 but did not affect the hypertrophic response measured at day 56. Hypoxia early reduced the phosphorylation levels of mTOR and its downstream targets P70(S6K) and rpS6, but it did not affect the phosphorylation levels of Akt and 4E-BP1, in Ov muscles. The role played by specific inhibitors of mTOR, such as AMPK and hypoxia-induced factors (i.e., REDD1 and BNIP-3) was studied. REDD1 protein levels were reduced by overload and were not affected by hypoxia in Ov muscles, whereas AMPK was not activated by hypoxia. Although hypoxia significantly increased BNIP-3 mRNA levels at day 5, protein levels remained unaffected. The mRNA levels of the two atrogenes MURF1 and MAFbx were early increased by hypoxia in Ov muscles. In conclusion, hypoxia induced a transient alteration of muscle growth in this hypertrophic model, at least partly due to a specific impairment of the mTOR/P70(S6K) pathway, independently of Akt, by an undefined mechanism, and increased transcript levels for MURF1 and MAFbx that could contribute to stimulate the proteasomal proteolysis.
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Hipóxia/fisiopatologia , Músculo Esquelético/patologia , Músculo Esquelético/fisiopatologia , Transdução de Sinais/fisiologia , Suporte de Carga/fisiologia , Animais , Feminino , Hipertrofia , Hipóxia/metabolismo , Modelos Animais , Proteínas Musculares/metabolismo , Músculo Esquelético/metabolismo , Proteólise , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Wistar , Proteínas Quinases S6 Ribossômicas 70-kDa/metabolismo , Proteínas Ligases SKP Culina F-Box/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Proteínas com Motivo Tripartido , Ubiquitina-Proteína Ligases/metabolismoRESUMO
The iron regulatory peptide hormone hepcidin has been proposed to participate in training-induced iron deficiency. Plasma and urinary hepcidin increase in response to one bout of prolonged exercise, a condition also known to increase plasma interleukin-6 (Il-6). Because Il-6 activates hepcidin transcription and expression during inflammation, our aim was to study the role of this cytokine in hepatic hepcidin mRNA expression during exercise and recovery. We used a rodent model of exhaustive running exercise, where rats were treated or not with cyclosporin A (CsA), a calcineurin inhibitor shown to blunt plasma Il-6 during exercise. Despite similar running intensity and duration, animals treated with CsA had 50% lower plasma Il-6 concentrations at the end of exercise. The concomitant rise in hepatic mRNA levels of two Il-6 responsive genes, suppressor of cytokine signaling (SOCS) 3 and Il-6 receptor alpha, was blunted in CsA-treated group. Finally, hepcidin mRNA levels increased in response to exercise, peaking 2h later, but peak values were significantly lower in CsA group compared to control group. This result strongly suggests that plasma Il-6 is involved in exercise-induced increase of hepcidin gene expression.
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Peptídeos Catiônicos Antimicrobianos/genética , Interleucina-6/fisiologia , Condicionamento Físico Animal , RNA Mensageiro/metabolismo , Animais , Sequência de Bases , Ciclosporina/administração & dosagem , Primers do DNA , Hepcidinas , Interleucina-6/sangue , Interleucina-6/genética , RNA Mensageiro/genética , Ratos , Ratos Wistar , Transcrição Gênica/efeitos dos fármacosRESUMO
In the course of their missions or training, alpinists, but also mountain combat forces and mountain security services, professional miners, aircrew, aircraft and glider pilots and helicopter crews are regularly exposed to altitude without oxygen supplementation. At altitude, humans are exposed to systemic environmental hypoxia induced by the decrease in barometric pressure (<1,013 hPa) which decreases the inspired partial pressure of oxygen (PIO2), while the oxygen fraction is constant (equal to approximately 20.9%). Effects of altitude on humans occur gradually and depend on the duration of exposure and the altitude level. From 1,500 m altitude (response threshold), several adaptive responses offset the effects of hypoxia, involving the respiratory and the cardiovascular systems, and the oxygen transport capacity of the blood. Fatigue and cognitive and sensory disorders are usually observed from 2,500 m (threshold of prolonged hypoxia). Above 3,500 m (the threshold for disorders), the effects are not completely compensated and maladaptive responses occur and individuals develop altitude headache or acute altitude illness [Acute Mountain Sickness (AMS)]. The magnitude of effects varies considerably between different physiological systems and exhibits significant inter-individual variability. In addition to comorbidities, the factors of vulnerability are still little known. They can be constitutive (genetic) or circumstantial (sleep deprivation, fatigue, speed of ascent.). In particular, sleep loss, a condition that is often encountered in real-life settings, could have an impact on the physiological and cognitive responses to hypoxia. In this review, we report the current state of knowledge on the impact of sleep loss on responses to environmental hypoxia in humans, with the aim of identifying possible consequences for AMS risk and cognition, as well as the value of behavioral and non-pharmacological countermeasures.
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This study investigates whether a functional single nucleotide polymorphism of HMOX2 (heme oxygenase-2) (rs4786504 T>C) is involved in individual chemosensitivity to acute hypoxia, as assessed by ventilatory responses, in European individuals. These responses were obtained at rest and during submaximal exercise, using a standardized and validated protocol for exposure to acute normobaric hypoxia. Carriers of the ancestral T allele (n = 44) have significantly lower resting and exercise hypoxic ventilatory responses than C/C homozygous carriers (n = 40). In the literature, a hypoxic ventilatory response threshold to exercise has been identified as an independent predictor of severe high altitude-illness (SHAI). Our study shows that carriers of the T allele have a higher risk of SHAI than carriers of the mutated C/C genotype. Secondarily, we were also interested in COMT (rs4680 G > A) polymorphism, which may be indirectly involved in the chemoreflex response through modulation of autonomic nervous system activity. Significant differences are present between COMT genotypes for oxygen saturation and ventilatory responses to hypoxia at rest. In conclusion, this study adds information on genetic factors involved in individual vulnerability to acute hypoxia and supports the critical role of the ⪠O2 sensor ⫠- heme oxygenase-2 - in the chemosensitivity of carotid bodies in Humans.
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The objective of this meta-analysis was to assess the effect of acute heat/cold exposure on subsequent energy intake (EI) in adults. We searched the following sources for publications on this topic: PubMed, Ovid Medline, Science Direct and SPORTDiscus. The eligibility criteria for study selection were: randomized controlled trials performed in adults (169 men and 30 women; 20-52 years old) comparing EI at one or more meals taken ad libitum, during and/or after exposure to heat/cold and thermoneutral conditions. One of several exercise sessions could be realized before or during thermal exposures. Two of the thirteen studies included examined the effect of heat (one during exercise and one during exercise and at rest), eight investigated the effect of cold (six during exercise and two at rest), and three the effect of both heat and cold (two during exercise and one at rest). The meta-analysis revealed a small increase in EI in cold conditions (g = 0.44; p = 0.019) and a small decrease in hot conditions (g = -0.39, p = 0.022) for exposure during both rest and exercise. Exposures to heat and cold altered EI in opposite ways, with heat decreasing EI and cold increasing it. The effect of exercise remains unclear.
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Temperatura Baixa , Ingestão de Energia , Exposição Ambiental , Exercício Físico , Temperatura Alta , Descanso , Metabolismo Energético , Exposição Ambiental/efeitos adversos , Feminino , Avaliação do Impacto na Saúde , Humanos , Masculino , RefeiçõesRESUMO
Aerobic training leads to well-known systemic metabolic and muscular alterations. Heat acclimation may also increase mitochondrial muscle mass. We studied the effects of heat acclimation combined with endurance training on metabolic adaptations of skeletal muscle. Thirty-two rats were divided into four groups: control (C), trained (T), heat-acclimated (H), and trained with heat acclimation (H+T) for 6 weeks. Soleus muscle metabolism was studied, notably by the in situ measurement of mitochondrial respiration with pyruvate (Pyr) or palmitoyl-coenzyme A (PCoA), under phosphorylating conditions ( VËmax ) or not ( VË0 ). Aerobic performance increased, and retroperitoneal fat mass decreased with training, independently of heat exposure (p < 0.001 and p < 0.001, respectively). Citrate synthase and hydroxyl-acyl-dehydrogenase activity increased with endurance training (p < 0.001 and p < 0.01, respectively), without any effect of heat acclimation. Training induced an increase of the VË0 and VËmax for PCoA (p < .001 and p < .01, respectively), without interference with heat acclimation. The training-induced increase of VË0 (p < 0.01) for pyruvate oxidation was limited when combined with heat acclimation (-23%, p < 0.01). Training and heat acclimation independently increased the VËmax for pyruvate (+60% p < 0.001 and +50% p = 0.01, respectively), without an additive effect of the combination. Heat acclimation doubled the training effect on muscle glycogen storage (p < 0.001). Heat acclimation did not improve mitochondrial adaptations induced by endurance training in the soleus muscle, possibly limiting the alteration of carbohydrate oxidation while not facilitating fatty-acid utilization. Furthermore, the increase in glycogen storage observed after HA combined with endurance training, without the improvement of pyruvate oxidation, appears to be a hypoxic metabolic phenotype.
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Músculo Esquelético/fisiologia , Condicionamento Físico Animal/métodos , Esforço Físico , Termotolerância , Adiposidade , Animais , Respiração Celular , Ácidos Graxos/metabolismo , Glicogênio/metabolismo , Masculino , Mitocôndrias Musculares/metabolismo , Músculo Esquelético/metabolismo , Consumo de Oxigênio , Ácido Pirúvico/metabolismo , Ratos , Ratos WistarRESUMO
Altitude camps are used during the preparation of endurance athletes to improve performance based on the stimulation of erythropoiesis by living at high altitude. In addition to such whole-body adaptations, studies have suggested that high-altitude training increases mitochondrial mass, but this has been challenged by later studies. Here, we hypothesized that living and training at high altitude (LHTH) improves mitochondrial efficiency and/or substrate utilization. Female rats were exposed and trained in hypoxia (simulated 3,200 m) for 5 weeks (LHTH) and compared to sedentary rats living in hypoxia (LH) or normoxia (LL) or those that trained in normoxia (LLTL). Maximal aerobic velocity (MAV) improved with training, independently of hypoxia, whereas the time to exhaustion, performed at 65% of MAV, increased both with training (P = 0.009) and hypoxia (P = 0.015), with an additive effect of the two conditions. The distance run was 7.98 ± 0.57 km in LHTH vs. 6.94 ± 0.51 in LLTL (+15%, ns). The hematocrit increased >20% with hypoxia (P < 0.001). The increases in mitochondrial mass and maximal oxidative capacity with endurance training were blunted by combination with hypoxia (-30% for citrate synthase, P < 0.01, and -23% for Vmax glut-succ, P < 0.001 between LHTH and LLTL). A similar reduction between the LHTH and LLTL groups was found for maximal respiration with pyruvate (-29%, P < 0.001), for acceptor-control ratio (-36%, hypoxia effect, P < 0.001), and for creatine kinase efficiency (-48%, P < 0.01). 3-hydroxyl acyl coenzyme A dehydrogenase was not altered by hypoxia, whereas maximal respiration with Palmitoyl-CoA specifically decreased. Overall, our results show that mitochondrial adaptations are not involved in the improvement of submaximal aerobic performance after LHTH, suggesting that the benefits of altitude camps in females relies essentially on other factors, such as the transitory elevation of hematocrit, and should be planned a few weeks before competition and not several months.
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Unbalanced energy partitioning participates in the rise of obesity, a major public health concern in many countries. Increasing basal energy expenditure has been proposed as a strategy to fight obesity yet raises efficiency and safety concerns. Here, we show that mice deficient for a muscle-specific enzyme of very-long-chain fatty acid synthesis display increased basal energy expenditure and protection against high-fat diet-induced obesity. Mechanistically, muscle-specific modulation of the very-long-chain fatty acid pathway was associated with a reduced content of the inner mitochondrial membrane phospholipid cardiolipin and a blunted coupling efficiency between the respiratory chain and adenosine 5'-triphosphate (ATP) synthase, which was restored by cardiolipin enrichment. Our study reveals that selective increase of lipid oxidative capacities in skeletal muscle, through the cardiolipin-dependent lowering of mitochondrial ATP production, provides an effective option against obesity at the whole-body level.
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A basal heat stress test (HST) to predict the magnitude of adaptive responses during heat acclimatization (HA) would be highly useful for the armed forces. The aim was to identify physiological markers assessed during a HST (three 8-min running sets at 50% of the speed at VO2max) performed just before a 14-day HA period that would identify participants still at "risk" at the end of HA. Individuals that responded poorly (large increases in rectal temperature [Trec] and heart rate [HR]) during the initial HST were more likely to respond favorably to HA (large reductions in Trec and HR). However, they were also more likely to exhibit lower tolerance to HST at D15. Basal Trec was found to efficiently discriminate participants showing a Trec > 38.5°C after HA, who are considered to be "at risk". Finally, participants were classified by quartiles based on basal Trec and HR at the end of the HST and physiological strain index (PSI). Most of the participants "at risk" were among the upper quartile (i.e. the least tolerant) of Trec and PSI (p = 0.011 for both). Overall, these results show that the individuals who are less tolerant to a basal HST are very likely to benefit the most from HA but they also remain less tolerant to heat at the end of HA than those who better tolerated the basal HST. A basal HST could therefore theoretically help the command to select the most-ready personnel in hot conditions while retaining those who are less tolerant 6.
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Benefits obtained after heat acclimation/acclimatization should be completely lost after an estimated period of 6 weeks. However, this estimate is still hypothetical. We evaluate the long-term effects of heat acclimatization on the level of heat tolerance. Physiological and subjective markers of heat tolerance were assessed during a heat stress test (HST: 3 × 8-min runs outdoors [~ 40 °C and 20% RH] at 50% of their estimated speed at VO2max) performed on the 2nd day upon arrival to the desert military base in the United Arab Emirates after a first day of mostly passive exposure to heat. Among the 50 male French soldiers, 25 partook in a 4-month military mission in countries characterized by a hot environment ~ 6 months prior to the study (HA). The other 25 participants were never heat acclimatized (CT). Rectal temperature (p = 0.023), heart rate (p = 0.033), and perceived exertion (p = 0.043) were lower in the HA than CT group at the end of HST. Soldiers who experienced a former 4-month period of natural heat acclimatization very likely had a higher level of heat tolerance during exercise in the heat, even 6 months after returning from the previous desert mission, than that of their non-acclimatized counterparts.
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Aclimatação/fisiologia , Temperatura Alta , Termotolerância , Adulto , Temperatura Corporal , Frequência Cardíaca , Humanos , Masculino , Esforço FísicoRESUMO
Myostatin, a member of the TGF-beta family, has been identified as a master regulator of embryonic myogenesis and early postnatal skeletal muscle growth. However, cumulative evidence also suggests that alterations in skeletal muscle mass are associated with dysregulation in myostatin expression and that myostatin may contribute to muscle mass loss in adulthood. Two major branches of the Akt pathway are relevant for the regulation of skeletal muscle mass, the Akt/mammalian target of rapamycin (mTOR) pathway, which controls protein synthesis, and the Akt/forkhead box O (FOXO) pathway, which controls protein degradation. Here, we provide further insights into the mechanisms by which myostatin regulates skeletal muscle mass by showing that myostatin negatively regulates Akt/mTOR signaling pathway. Electrotransfer of a myostatin expression vector into the tibialis anterior muscle of Sprague Dawley male rats increased myostatin protein level and decreased skeletal muscle mass 7 d after gene electrotransfer. Using RT-PCR and immunoblot analyses, we showed that myostatin overexpression was ineffective to alter the ubiquitin-proteasome pathway. By contrast, myostatin acted as a negative regulator of Akt/mTOR pathway. This was supported by data showing that the phosphorylation of Akt on Thr308, tuberous sclerosis complex 2 on Thr1462, ribosomal protein S6 on Ser235/236, and 4E-BP1 on Thr37/46 was attenuated 7 d after myostatin gene electrotransfer. The data support the conclusion that Akt/mTOR signaling is a key target that accounts for myostatin function during muscle atrophy, uncovering a novel role for myostatin in protein metabolism and more specifically in the regulation of translation in skeletal muscle.
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Músculo Esquelético/fisiologia , Miostatina/genética , Proteínas Quinases/genética , Animais , Atrofia , DNA/genética , Primers do DNA , Regulação para Baixo , Masculino , Músculo Esquelético/patologia , Plasmídeos/genética , Biossíntese de Proteínas , Proteínas Proto-Oncogênicas c-akt/genética , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Serina-Treonina Quinases TORRESUMO
In the present study, we tested the hypothesis that chronic ANG I-converting enzyme (ACE) inhibition could improve the training-induced improvement in endurance exercise performance and that this could be related to enhanced skeletal muscle metabolic efficiency. Female Wistar rats were assigned to four groups comprising animals either maintained sedentary or endurance trained (Sed and Tr, respectively), and treated or not for 10 wk with an ACE inhibitor, perindopril (2 mg.kg(-1).day(-1)) (Per and Ct, respectively) (n = 8 each). Trained rats underwent an 8-wk treadmill training protocol that consisted of 2 h/day running at 30 m/min on a 8% decline. Before the start of and 1 wk before the end of experimental conditioning, the running time to exhaustion of rats was measured on a treadmill. The training program led to an increase in endurance time, higher in Tr-Per than in Tr-Ct group (125% in Tr-Ct vs. 183% in Tr-Per groups, P < 0.05). Oxidative capacity, measured in saponin-permeabilized fibers of slow soleus and fast plantaris muscles, increased with training, but less in Tr-Per than in Tr-Ct rats. The training-induced increase in citrate synthase activity also was less in soleus from Tr-Per than Tr-Ct rats. The training-induced increase in the percentage of the type IIa isoform of myosin heavy chain (MHC) (45%, P < 0.05) and type IIx MHC (25%, P < 0.05) associated with decreased type IIb MHC (34%, P < 0.05) was minimized by perindopril administration. These findings demonstrate that the enhancement in physical performance observed in perindopril-treated animals cannot be explained by changes in mitochondrial respiration and/or MHC distribution within muscles involved in running exercise.
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Fibras Musculares Esqueléticas/citologia , Fibras Musculares Esqueléticas/enzimologia , Consumo de Oxigênio/fisiologia , Peptidil Dipeptidase A/metabolismo , Condicionamento Físico Animal/fisiologia , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Animais , Citrato (si)-Sintase/metabolismo , Feminino , Mitocôndrias Musculares/efeitos dos fármacos , Mitocôndrias Musculares/enzimologia , Atividade Motora/efeitos dos fármacos , Atividade Motora/fisiologia , Contração Muscular/efeitos dos fármacos , Contração Muscular/fisiologia , Fibras Musculares de Contração Rápida/efeitos dos fármacos , Fibras Musculares de Contração Rápida/metabolismo , Fibras Musculares Esqueléticas/efeitos dos fármacos , Fibras Musculares de Contração Lenta/efeitos dos fármacos , Fibras Musculares de Contração Lenta/metabolismo , Cadeias Pesadas de Miosina/efeitos dos fármacos , Cadeias Pesadas de Miosina/metabolismo , Consumo de Oxigênio/efeitos dos fármacos , Perindopril/farmacologia , Fenótipo , Esforço Físico/efeitos dos fármacos , Esforço Físico/fisiologia , Ratos , Ratos WistarRESUMO
We investigated the effect of temperature increase on mitochondrial fatty acid (FA) and carbohydrate oxidation in the slow-oxidative skeletal muscles (soleus) of rats. We measured mitochondrial respiration at 35°C and 40°C with the physiological substrates pyruvate + 4 mM malate (Pyr) and palmitoyl-CoA (PCoA) + 0.5 mM malate + 2 mM carnitine in permeabilized myofibers under nonphosphorylating (VË0) or phosphorylating (VËmax) conditions. Mitochondrial efficiency was calculated by the respiratory control ratio (RCR = VËmax/VË0). We used guanosine triphosphate (GTP), an inhibitor of uncoupling protein (UCP), to study the mechanisms responsible for alterations of mitochondrial efficiency. We measured hydrogen peroxide (H2O2) production under nonphosphorylating and phosphorylating conditions at both temperatures and substrates. We studied citrate synthase (CS) and 3-hydroxyl acyl coenzyme A dehydrogenase (3-HAD) activities at both temperatures. Elevating the temperature from 35°C to 40°C increased PCoA-VË0 and decreased PCoA-RCR, corresponding to the uncoupling of oxidative phosphorylation (OXPHOS). GTP blocked the heat-induced increase of PCoA-VË0. Rising temperature moved toward a Pyr-VË0 increase, without significance. Heat did not alter H2O2 production, resulting from either PCoA or Pyr oxidation. Heat induced an increase in 3-HAD but not in CS activities. In conclusion, heat induced OXPHOS uncoupling for PCoA oxidation, which was at least partially mediated by UCP and independent of oxidative stress. The classically described heat-induced glucose shift may actually be mostly due to a less efficient FA oxidation. These findings raise questions concerning the consequences of heat-induced alterations in mitochondrial efficiency of FA metabolism on thermoregulation.NEW & NOTEWORTHY Ex vivo exposure of skeletal myofibers to heat uncouples substrate oxidation from ADP phosphorylation, decreasing the efficiency of mitochondria to produce ATP. This heat effect alters fatty acids (FAs) more than carbohydrate oxidation. Alteration of FA oxidation involves uncoupling proteins without inducing oxidative stress. This alteration in lipid metabolism may underlie the preferential use of carbohydrates in the heat and could decrease aerobic endurance.
Assuntos
Ácidos Graxos/metabolismo , Mitocôndrias Musculares/metabolismo , Miofibrilas/metabolismo , Animais , Carnitina/metabolismo , Respiração Celular/fisiologia , Citrato (si)-Sintase/metabolismo , Glucose/metabolismo , Peróxido de Hidrogênio/metabolismo , Metabolismo dos Lipídeos/fisiologia , Malatos/metabolismo , Masculino , Proteínas Mitocondriais/metabolismo , Músculo Esquelético/metabolismo , Oxirredução , Fosforilação Oxidativa , Estresse Oxidativo/fisiologia , Consumo de Oxigênio/fisiologia , Palmitoil Coenzima A/metabolismo , Ácido Pirúvico/metabolismo , Ratos , Ratos Wistar , TemperaturaRESUMO
MicroRNAs (miRNA) are small non-coding RNAs that target mRNAs and are consequently involved in the post-transcriptional regulation of gene expression. Some miRNAs are ubiquitously expressed in tissue, while others are tissue-specific or tissue-enriched. miRNAs can be released by cells and are found in various biofluids, including serum and plasma. Thus, measuring miRNAs in the circulation may provide information on the originating tissue or cells. MyomiRs are described as striated muscle-specific or muscle-enriched miRNAs. Their circulating levels can be measured and have been proposed to be new biomarkers of physiological and pathological muscle processes. The aims of this review are to summarize the current knowledge of circulating myomiRs, to identify the types of information they can provide about skeletal muscle, and to determine how to apply that information in the fields of research and medicine.