Changes In Oxidative Capacity Research Articles

High-intensity exercise training using a rotarod instrument (RotaHIIT)significantly improves exercise capacity in mice.

Voluntary or forced exercise training in mice is used to assess functional capacity as well as potential disease-modifying effects of exercise over a range of cardiovascular disease phenotypes. Compared to voluntary wheel running, forced exercise training enables precise control of exercise workload and volume, and results in superior changes in cardiovascular performance. However, the use of a shock grid with treadmill-based training is associated with stress and risk of injury, and declining compliance with longer periods of training time for many mouse strains. With these limitations in mind, we designed a novel, high-intensity interval training modality (HIIT) for mice that is carried out on a rotarod. Abbreviated as RotaHIIT, this protocol establishes interval workload intensities that are not time or resource intensive, maintains excellent training compliance over time, and results in improved exercise capacity independent of sex when measured by treadmill graded exercise testing (GXT) and rotarod specific acceleration and endurance testing. This protocol may therefore be useful and easily implemented for a broad range of research investigations. As RotaHIIT training was not associated cardiac structural or functional changes, or changes in oxidative capacity in cardiac or skeletal muscle tissue, further studies will be needed to define the physiological adaptations and molecular transducers that are driving the training effect of this exercise modality.

Male and Female Mitochondria Respond Differently after Exercising in Acute Hypoxia.

The use of hypoxic devices among athletes who train in normobaric hypoxia has become increasingly popular; however, the acute effects on heart and brain metabolism are not yet fully understood. This study aimed to investigate the mitochondrial bioenergetics in trained male and female Wistar rats after acute hypoxia training. The experimental plan included exercising for 30 min on a treadmill in a Plexiglas cage connected to a hypoxic generator set at 12.5% O2 or in normoxia. After the exercise, the rats were sacrificed, and their mitochondria were isolated from their brains and hearts. The bioenergetics for each complex of the electron transport chain was tested using a Clark-type electrode. The results showed that following hypoxia training, females experienced impaired oxidative phosphorylation through complex II in heart subsarcolemmal mitochondria, while males had an altered ADP/O in heart interfibrillar mitochondria, without any change in oxidative capacity. No differences from controls were evident in the brain, but an increased electron transport system efficiency was observed with complex I and IV substrates in males. Therefore, the study's findings suggest that hypoxia training affects the heart mitochondria of females more than males. This raises a cautionary flag for female athletes who use hypoxic devices.

Muscle PGC-1α modulates hepatic mitophagy regulation during aging

Aging has been suggested to be associated with changes in oxidative capacity, autophagy, and mitophagy in the liver, but a simultaneous evaluation of these key cellular processes is lacking. Moreover, skeletal muscle transcriptional coactivator peroxisome proliferator-activated receptor gamma coactivator (PGC)-1α has been reported to mediate inter-organ signaling through myokines with regulatory effects in the liver, but the potential role of muscle PGC-1α on hepatic changes with age remains to be resolved. The aim of the present study was therefore to investigate 1) the effect of aging on mitochondrial autophagy and mitophagy capacity in mouse liver and 2) whether muscle PGC-1α is required for maintaining autophagy and mitophagy capacity in the liver during aging. The liver was obtained from young (Young) and aged (Aged) inducible muscle-specific PGC-1α knockout (iMKO) and floxed littermate control mice (Lox). Aging increased liver p62, Parkin and BCL2/adenovirus E1B 19 kDa protein-interacting protein (BNIP)3 protein with no effect of muscle specific PGC-1α knockout, while liver Microtubule-associated protein 1A/1B-light chain 3(LC3) II/I was unchanged with age, but tended to be lower in iMKO mice than in controls. Markers of liver mitochondrial oxidative capacity and oxidative stress were unchanged with age and iMKO. However, Parkin protein levels in isolated liver mitochondria were 2-fold higher in Aged iMKO mice than in Aged controls. In conclusion, aging had no effect on oxidative capacity and lipid peroxidation in the liver. However, aging was associated with increased levels of autophagy and mitophagy markers. Moreover, muscle PGC-1α appears to regulate hepatic mitochondrial translocation of Parkin in aged mice, suggesting that the metabolic capacity of skeletal muscle can modulate mitophagy regulation in the liver during aging.

Early Deconditioning of Human Skeletal Muscles and the Effects of a Thigh Cuff Countermeasure.

Muscle deconditioning is a major consequence of a wide range of conditions from spaceflight to a sedentary lifestyle, and occurs as a result of muscle inactivity, leading to a rapid decrease in muscle strength, mass, and oxidative capacity. The early changes that appear in the first days of inactivity must be studied to determine effective methods for the prevention of muscle deconditioning. To evaluate the mechanisms of muscle early changes and the vascular effect of a thigh cuff, a five-day dry immersion (DI) experiment was conducted by the French Space Agency at the MEDES Space Clinic (Rangueil, Toulouse). Eighteen healthy males were recruited and divided into a control group and a thigh cuff group, who wore a thigh cuff at 30 mmHg. All participants underwent five days of DI. Prior to and at the end of the DI, the lower limb maximal strength was measured and muscle biopsies were collected from the vastus lateralis muscle. Five days of DI resulted in muscle deconditioning in both groups. The maximal voluntary isometric contraction of knee extension decreased significantly. The muscle fiber cross-sectional area decreased significantly by 21.8%, and the protein balance seems to be impaired, as shown by the reduced activation of the mTOR pathway. Measurements of skinned muscle fibers supported these results and potential changes in oxidative capacity were highlighted by a decrease in PGC1-α levels. The use of the thigh cuff did not prevent muscle deconditioning or impact muscle function. These results suggest that the major effects of muscle deconditioning occur during the first few days of inactivity, and countermeasures against muscle deconditioning should target this time period. These results are also relevant for the understanding of muscle weakness induced by muscle diseases, aging, and patients in intensive care.

The effects of physical prehabilitation: Improved liver regeneration and mitochondrial function after ALPPS operation in a rodent model.

To identify the role of physical prehabilitation (PP) in liver regeneration, mitochondrial function, biogenesis, and inflammatory response was investigated after associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) in a rodent model. Male Wistar rats (n=60) underwent ALPPS. Animals were divided (n=30) to the physical prehabilitation group (PP) and sedentary group (S). The animals were exsanguinated before (0hour) and 24, 48, 72, or 168hours after the operation. Regeneration rate and proliferation index were assessed. Mitochondrial function, biogenesis, and inflammatory response were evaluated. Regeneration rate and Ki67 index were significantly increased in the PP group compared to the S group (P<.001). Due to the changes in oxidative capacity and ATP production rate, the P/O ratio of PP group compared to the S group was significantly increased (P<.05). PP group was characterized by accelerated mitochondrial biogenesis and less intense inflammatory response compared to the S group. To our knowledge, this is the first demonstration of the beneficial effects of PP on liver regeneration, mitochondrial function, biogenesis, and the inflammatory response after ALPPS.

Effect of continuous positive airway pressure on maximal exercise capacity in patients with obstructive sleep apnea: a systematic review and meta-analysis.

Exercise capacity is impaired in obstructive sleep apnea (OSA). There are conflicting reports on the effect of continuous positive airway pressure (CPAP) on maximal exercise capacity. The objective of this review was to determine if there is a change in exercise capacity and anaerobic threshold following CPAP treatment in OSA patients. We conducted a systematic review and meta-analyses to summarize the changes in peak rate of oxygen uptake (V̇O₂ peak) or maximum rate of oxygen uptake (V̇O2 max) and anaerobic threshold (AT) during cardiopulmonary exercise testing following CPAP intervention in patients with OSA. A systematic literature review was conducted to identify published literature on markers of V̇O₂ peak, V̇O₂ max, and AT pre- vs post-CPAP using a web-based literature search of PubMed/MEDLINE, Embase, CINAHL, and Cochrane review (CENTRAL) databases. Two independent reviewers screened the articles for data extraction and analysis. The total search of all the databases returned 470 relevant citations. Following application of eligibility criteria, 6 studies were included in the final meta-analysis for V̇O₂ peak, 2 studies for V̇O₂ max, and five studies for AT. The meta-analysis showed a mean net difference in V̇O₂ peak between pre- and post-CPAP of 2.69 mL·kg-1·min-1, P = .02, favoring treatment with CPAP. There was no difference in V̇O₂ max or AT with CPAP treatment (mean net difference 0.66 mL·kg-1·min-1 [P = .78] and -144.98 mL·min-1 [P = .20] respectively). There is a paucity of high-quality studies investigating the effect of CPAP on exercise capacity. Our meta-analysis shows that V̇O₂ peak increases following CPAP treatment in patients with OSA, but we did not observe any change in V̇O₂ max or AT. Our findings should be considered preliminary and we recommend further randomized controlled trials to confirm our findings and to clarify the peak and maximum rates of oxygen uptake adaptations with CPAP therapy.

Abstract 278: Dual Modulation of Microscale Tissue Engineering and Energy Metabolism for Maturation of Human Pluripotent Stem Cell-Derived Cardiomyocytes

Background: Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) represent a viable cell source for clinical application and other purposes, such as disease modeling and drug discovery for cardiovascular diseases. However, their immature phenotype limits their utility for these applications. It is widely known that the transition from fetal to adult heart during development is accompanied by an alteration in energy metabolism from glycolysis to fatty acid oxidation (FAO), respectively. Using this metabolic hallmark of cardiomyocyte maturation, we investigated a platform that combines three-dimensional (3D) cell cultivation and molecules that target key pathways involved in the energy metabolism of cardiomyocytes. Methods: Cardiac spheres of highly-enriched hPSC-CMs were generated from cardiac-differentiated cultures and treated with a combination of five molecules or control (DMSO) for one week. We used functional, morphological, transcriptome and metabolome analyses to assess the maturation status of hPSC-CMs. RESULTS: Treatment of 3D hPSC-CMs with a combination of five molecules elicited increased FAO along with mitochondrial respiratory capacity. These changes in oxidative capacity were associated with increased mitochondrial content and DNA. In addition, cardiac spheres treated with combined molecules displayed enhanced calcium transient kinetics when compared to control cells. RNA sequencing revealed upregulation of genes involved in many cellular metabolic processes, including FAO. Lastly, metabolic profiling of these cardiac spheres identified more than one hundred metabolites that were altered upon treatment. Conclusions: Our study showed that microscale tissue engineering along with treatment of hPSC-CMs with a combination of five molecules increase mitochondrial function, alter molecular and metabolic profiles, and potentially improve cardiomyocyte maturation.

Time course of denervation-induced changes in gastrocnemius muscles of adult and old rats

Denervation leads to significant muscle atrophy, but it is less clear whether 1) loss of capillaries, fibre size and oxidative capacity decline in parallel and 2) the time course of these changes differs between young and old animals. To investigate this, we denervated the left gastrocnemius muscle for 1, 2 or 4 weeks, while the right muscle served as an internal control, in rats that were 5 or 25 months old at the end of the experiment. In the fast part of the gastrocnemius muscle, almost all atrophy had occurred after two weeks (42%) of denervation. Even after 4 weeks of denervation, there was no significant reduction in the oxidative capacity of the muscle. Significant capillary loss occurred only after 4 weeks of denervation (P < 0.001) that lagged behind and was less than proportional to the decrease in fibre size. Consequently, the capillary density was elevated (P < 0.001). The time course of these morphological changes was similar in the 5- and 25-month-old rats. Comparing these data with those previously published in the soleus muscle from the same animals show that the decrease in oxidative capacity and capillary rarefaction were more pronounced and occurred earlier than in the gastrocnemius muscle, respectively. The time course of capillary loss lagged behind the decrease in fibre size, and combined with the absence of denervation-induced changes in oxidative capacity this resulted in a muscle capillary supply in excess of that expected by the metabolism and fibre size at least during the first 4 weeks after denervation.

In vivo mitochondrial function in aging skeletal muscle: capacity, flux, and patterns of use.

Because of the fundamental dependence of mammalian life on adequate mitochondrial function, the question of how and why mitochondria change in old age is the target of intense study. Given the importance of skeletal muscle for the support of mobility and health, this question extends to the need to understand mitochondrial changes in the muscle of older adults, as well. We and others have focused on clarifying the age-related changes in human skeletal muscle mitochondrial function in vivo. These changes include both the maximal capacity for oxidative production of energy (ATP), as well as the relative use of mitochondrial ATP production for powering muscular activity. It has been known for nearly 50 yr that muscle mitochondrial content is highly plastic; exercise training can induce an ∼2-fold increase in mitochondrial content, while disuse has the opposite effect. Here, we suggest that a portion of the age-related changes in mitochondrial function that have been reported are likely the result of behavioral effects, as physical activity influences have not always been accounted for. Further, there is emerging evidence that various muscles may be affected differently by age-related changes in physical activity and movement patterns. In this review, we will focus on age-related changes in oxidative capacity and flux measured in vivo in human skeletal muscle.

Use of electromyography to detect muscle exhaustion in finishing barrows fed ractopamine HCl.

The objectives of this study were to determine the effects of dietary ractopamine HCl (RAC) on muscle fiber characteristics and electromyography (EMG) measures of finishing barrow exhaustion when barrows were subjected to increased levels of activity. Barrows ( = 34; 92 ± 2 kg initial BW) were assigned to 1 of 2 treatments: a conventional swine finishing diet containing 0 mg/kg ractopamine HCl (CON) or a diet formulated to meet the requirements of finishing barrows fed 10 mg/kg RAC (RAC+). After 32 d on feed, barrows were individually moved around a track at 0.79 m/s until subjectively exhausted. Wireless EMG sensors were affixed to the deltoideus (DT), triceps brachii lateral head (TLH), tensor fasciae latae (TFL), and semitendinosus (ST) muscles to measure median power frequency (MdPF) and root mean square (RMS) as indicators of action potential conduction velocity and muscle fiber recruitment, respectively. After harvest, samples of each muscle were collected for fiber type, succinate dehydrogenase (SDH), and capillary density analysis. Speed was not different ( = 0.82) between treatments, but RAC+ barrows reached subjective exhaustion earlier and covered less distance than CON barrows ( < 0.01). There were no treatment × muscle interactions or treatment effects for end-point MdPF values ( > 0.29). There was a treatment × muscle interaction ( = 0.04) for end-point RMS values. The RAC diet did not change end-point RMS values in the DT or TLH ( > 0.37); however, the diet tended to decrease and increase end-point RMS in the ST and TFL, respectively ( < 0.07). There were no treatment × muscle interactions for fiber type, SDH, or capillary density measures ( > 0.10). Muscles of RAC+ barrows tended to have less type I fibers and more capillaries per fiber ( < 0.07). Type I and IIA fibers of RAC+ barrows were larger ( < 0.07). Compared with all other muscles, the ST had more ( < 0.01) type IIB fibers and larger type I, IIA, and IIX fibers ( < 0.01). Type I, IIA, and IIX fibers of the ST also contained less SDH compared with the other muscles ( < 0.01). Barrows fed a RAC diet had increased time to subjective exhaustion due to loss of active muscle fibers in the ST, possibly due to fibers being larger and less oxidative in metabolism. Size increases in type I and IIA fibers with no change in oxidative capacity could also contribute to early exhaustion of RAC+ barrows. Overall, EMG technology can measure real-time muscle fiber loss to help explain subjective exhaustion in barrows.

Reduced skeletal muscle oxidative capacity and impaired training adaptations in heart failure.

Systolic heart failure (HF) is associated with exercise intolerance that has been attributed, in part, to skeletal muscle dysfunction. The purpose of this study was to compare skeletal muscle oxidative capacity and training-induced changes in oxidative capacity in participants with and without HF. Participants with HF (n = 16, 65 ± 6.6 years) were compared with control participants without HF (n = 23, 61 ± 5.0 years). A subset of participants (HF: n = 7, controls: n = 5) performed 4 weeks of wrist-flexor exercise training. Skeletal muscle oxidative capacity was determined from the recovery kinetics of muscle oxygen consumption measured by near-infrared spectroscopy (NIRS) following a brief bout of wrist-flexor exercise. Oxidative capacity, prior to exercise training, was significantly lower in the HF participants in both the dominant (1.31 ± 0.30 min−1 vs. 1.59 ± 0.25 min−1, P = 0.002; HF and control groups, respectively) and nondominant arms (1.29 ± 0.24 min−1 vs. 1.46 ± 0.23 min−1, P = 0.04; HF and control groups, respectively). Following 4 weeks of endurance training, there was a significant difference in the training response between HF and controls, as the difference in oxidative training adaptations was 0.69 ± 0.12 min−1 (P < 0.001, 95% CI 0.43, 0.96). The wrist-flexor training induced a ∼50% improvement in oxidative capacity in participants without HF (mean difference from baseline = 0.66 ± 0.09 min−1, P < 0.001, 95% CI 0.33, 0.98), whereas participants with HF showed no improvement in oxidative capacity (mean difference from baseline = −0.04 ± 0.08 min−1, P = 0.66, 95% CI −0.24, 0.31), suggesting impairments in mitochondrial biogenesis. In conclusion, participants with HF had reduced oxidative capacity and impaired oxidative adaptations to endurance exercise compared to controls.

Abstracts

Muscle unloading, as encountered during space flight and disuse, induces skeletal muscle atrophy and weakness, switch of fibre types and loss of capillaries. Less attention has been given to disuse-induced changes in oxidative capacity, which may affect endurance. Here we investigated the impact of 21 days, 60 head-down bed rest on muscle fibre size, fibre type composition, capillarisation and muscle oxidative capacity and the efficacy of milk-based proteins (whey protein) to counteract disuse-induced muscle changes. Muscle biopsies were taken from the soleus (SOL) and vastus lateralis (VL)muscles before and after bed rest from10 healthy men (aged 31 ± 6 years). Subjects were assigned to two groups and studied twice in two follow-up campaigns, in once receiving whey protein and once receiving a standardized isocaloric diet. Fibre types and capillaries were identified by immunohistochemical staining of muscle section with anti-myosin type1 and lectin. Analysis was done with the method of capillary domains.Oxidative capacity of individual fibres was determined as the optical density (OD) at 660 nm of succinate dehydrogenase (SDH) stained histological sections. The fibre cross-sectional area times the SDH-OD of that fibre (integrated SDH) was index of maximal oxygen consumption of that fibre(VO2max). Statistical analysis was done by repeated measures ANOVA. Bed rest did not induce significant changes infibre type composition, fibre size or capillarisation, but decreased SDH activity (p\0.001) and fibre VO2max (p\0.01) in both muscles. Whey protein partially counteracted the decrease in oxidative capacity. Our results suggest that decrements in oxidative capacity may be an early hallmark of disuse-induced muscle adaptations and occurs even in the absence of significant fibre atrophy and capillary rarefaction. The Whey diet attenuated these effects and may thus be an effective supplement to sustain oxidative capacity during space flight and long-term bed rest.

Physicochemical characteristics, oxidative capacities and cytotoxicities of sulfate-coated, 1,4-NQ-coated and ozone-aged black carbon particles

Black carbon (BC) particles play important roles in climate change, visibility impairment, atmospheric reaction process, and health effect. The aging processes of BC alter not only atmospheric composition, but also the physicochemical characteristics of BC itself, thus impacting the environment and health effects. Here, three types of BC including sulfate-coated, 1,4-naphthoquinone (1,4-NQ)-coated, and O3-aged BC are presented. The morphologies, structures, extraction components, the amount of water-soluble organic carbon (WSOC) and free radical intensities of the three types of BC particles are examined by transmission electron microscopy, diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS), ultraviolet–visible spectrophotometry, total organic carbon detector and electron paramagnetic resonance, respectively. Dithiothreitol (DTT) and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide assays are utilized to assess the changes in oxidative capacity and cytotoxicity towards murine alveolar macrophage cells. The orders of DTT activities and cytotoxicities of the particles are both arranged as follows: BC/1,4-NQ>BC/O3>BC>BC/sulfate, mainly because 1,4-NQ owned high oxidative potential and cytotoxicity, while sulfate did not exhibit oxidative capacity and cytotoxicity. The insoluble components of particles contribute most of the total DTT activity, whereas either water or methanol extract is minor contributor. DTT activity was positively correlated with both WSOC content and free radical intensity, with the correlation between DTT activity and WSOC content was stronger than that between DTT activity and free radical intensity.

Resistance training increases skeletal muscle oxidative capacity and net intramuscular triglyceride breakdown in type I and II fibres of sedentary males

Recent in vitro and in vivo experimental observations suggest that improvements in insulin sensitivity following endurance training are mechanistically linked to increases in muscle oxidative capacity, intramuscular triglyceride (IMTG) utilization during endurance exercise and increases in the content of the lipid droplet-associated perilipin 2 (PLIN2) and perilipin 5 (PLIN5). This study investigated the hypothesis that similar adaptations may also underlie the resistance training (RT)-induced improvements in insulin sensitivity. Thirteen sedentary men (20 ± 1 years old; body mass index 24.8 ± 0.8 kg m(-2)) performed 6 weeks of whole-body RT (three times per week), and changes in peak O2 uptake (in millilitres per minute per kilogram) and insulin sensitivity were assessed. Muscle biopsies (n = 8) were obtained before and after 60 min steady-state cycling at ~65% peak O2 uptake. Immunofluorescence microscopy was used to assess changes in oxidative capacity (measured as cytochrome c oxidase protein content), IMTG and PLIN2 and PLIN5 protein content. Resistance training increased peak O2 uptake (by 8 ± 3%), COX protein content (by 46 ± 13 and 61 ± 13% in type I and II fibres, respectively) and the Matsuda insulin sensitivity index (by 47 ± 6%; all P < 0.05). In type I fibres, IMTG (by 52 ± 11%; P < 0.05) and PLIN2 content (by 107 ± 19%; P < 0.05) were increased and PLIN5 content tended to increase (by 54 ± 22%; P = 0.054) post-training. In type II fibres, PLIN2 content increased (by 57 ± 20%; P < 0.05) and IMTG (by 46 ± 17%; P = 0.1) and PLIN5 content (by 44 ± 24%; P = 0.054) tended to increase post-training. Breakdown of IMTG during moderate-intensity exercise was greater in both type I and type II fibres (by 43 ± 5 and 37 ± 5%, respectively; P < 0.05) post-RT. The results confirm the hypothesis that RT enhances muscle oxidative capacity and increases IMTG breakdown and the content of PLIN2 and PLIN5 in both type I and type II fibres during endurance-type exercise.

Transcriptional Assessment by Microarray Analysis and Large-Scale Meta-analysis of the Metabolic Capacity of Cardiac and Skeletal Muscle Tissues to Cope With Reduced Nutrient Availability in Gilthead Sea Bream (Sparus aurata L.)

The effects of nutrient availability on the transcriptome of cardiac and skeletal muscle tissues were assessed in juvenile gilthead sea bream fed with a standard diet at two feeding levels: (1) full ration size and (2) 70 % satiation followed by a finishing phase at the maintenance ration. Microarray analysis evidenced a characteristic transcriptomic profile for each muscle tissue following changes in oxidative capacity (heart > red skeletal muscle > white skeletal muscle). The transcriptome of heart and secondly that of red skeletal muscle were highly responsive to nutritional changes, whereas that of glycolytic white skeletal muscle showed less ability to respond. The highly expressed and nutritionally regulated genes of heart were mainly related to signal transduction and transcriptional regulation. In contrast, those of white muscle were enriched in gene ontology (GO) terms related to proteolysis and protein ubiquitination. Microarray meta-analysis using the bioinformatic tool Fish and Chips ( http://fishandchips.genouest.org/index.php ) showed the close association of a representative cluster of white skeletal muscle with some of cardiac and red skeletal muscle, and many GO terms related to mitochondrial function appeared to be common links between them. A second round of cluster comparisons revealed that mitochondria-related GOs also linked differentially expressed genes of heart with those of liver from cortisol-treated gilthead sea bream. These results show that mitochondria are among the first responders to environmental and nutritional stress stimuli in gilthead sea bream, and functional phenotyping of this cellular organelle is highly promising to obtain reliable markers of growth performance and well-being in this fish species.

Reducing the Intensity and Volume of Interval Training Diminishes Cardiovascular Adaptation but Not Mitochondrial Biogenesis in Overweight/Obese Men

ObjectiveThe purpose of this research was to determine if the adaptations to high intensity interval training (HIT) are mitigated when both intensity and training volume (i.e. exercise energy expenditure) are reduced.Methods19 overweight/obese, sedentary males (Age: 22.7±3.9 yrs, Body Mass Index: 31.4±2.6 kg/m2, Waist Circumference: 106.5±6.6 cm) performed 9 sessions of interval training using a 1-min on, 1-min off protocol on a cycle ergometer over three weeks at either 70% (LO) or 100% (HI) peak work rate.ResultsCytochrome oxidase I protein content, cytochrome oxidase IV protein content, and citrate synthase maximal activity all demonstrated similar increases between groups with a significant effect of training for each. β-hydroxyacyl-CoA dehydrogenase maximal activity tended to increase with training but did not reach statistical significance (p = 0.07). Peroxisome proliferator-activated receptor gamma coactivator-1α and silent mating type information regulator 2 homolog 1 protein contents also increased significantly (p = 0.047), while AMP-activated protein kinase protein content decreased following the intervention (p = 0.019). VO2peak increased by 11.0±7.4% and 27.7±4.4% in the LO and HI groups respectively with significant effects of both training (p<0.001) and interaction (p = 0.027). Exercise performance improved by 8.6±7.6% in the LO group and 14.1±4.3% in the HI group with a significant effect of training and a significant difference in the improvement between groups. There were no differences in perceived enjoyment or self-efficacy between groups despite significantly lower affect scores during training in the HI group.ConclusionsWhile improvements in aerobic capacity and exercise performance were different between groups, changes in oxidative capacity were similar despite reductions in both training intensity and volume.

Effect of hypoxia exposure on the phenotypic adaptation in remodelling skeletal muscle submitted to functional overload

To determine whether hypoxia influences the phenotypic adaptation of skeletal muscle induced by mechanical overload. Plantaris muscles of female rats were submitted to mechanical overload following synergist ablation. After 3 days of overload, rats were exposed to either hypobaric hypoxia (equivalent to 5500 m) or normoxia. Muscles were collected after 5, 12 and 56 days of overload (i.e. after 3, 9 and 53 days of hypoxia). We determined the myosin heavy chain (MHC) distribution, mRNA levels of myocyte-enriched calcineurin-integrating protein 1 (MCIP1) to indirectly assess calcineurin activity, the changes in oxidative capacity from the activities of citrate synthase (CS) and cytochrome c oxidase (COX), and the expression of regulators involved in mitochondrial biogenesis (Pgc-1α, NRF1 and Tfam) and degradation (BNIP-3). Hypoxia did not alter the fast-to-slow MHC shift and the increase in calcineurin activity induced by overload; it only transiently slowed down the overload-induced transition in MHC isoforms. Hypoxia similarly decreased CS and COX activities in overloaded and control muscles. Nuclear respiratory factor 1 (NRF1) and transcription factor A (Tfam) mRNA and BNIP-3 protein were not influenced by hypoxia in overloaded muscles, whereas Pgc-1α mRNA and protein contents did not correlate with changes in oxidative capacity. Hypoxia is not a critical stimulus to modulate the fast-to-slow MHC transition associated with overload. Thus, the impairment of the fast-to-slow fibre shift often observed during post-natal development in hypoxia could be explained by the lower voluntary locomotor activity associated with hypoxia. Hypoxia alters mitochondrial oxidative capacity, but this adaptive response is similar in overloaded and control muscles.

Changes in muscle composition during the development of diving ability in the Australian fur seal

During development the Australian fur seal transitions from a terrestrial, maternally dependent pup to an adult marine predator. Adult seals have adaptations that allow them to voluntarily dive at depth for long periods, including increased bradycardic control, increased myoglobin levels and haematocrit. To establish whether the profile of skeletal muscle also changes in line with the development of diving ability, biopsy samples were collected from the trapezius muscle of pups, juveniles and adults. The proportions of different fibre types and their oxidative capacity were determined. Only oxidative fibre types (Type I and IIa) were identified, with a significant change in proportions from pup to adult. There was no change in oxidative capacity of Type I and IIa fibres between pups and juveniles but there was a two-fold increase between juveniles and adults. Myoglobin expression increased between pups and juveniles, suggesting improved oxygen delivery, but with no increase in oxidative capacity, oxygen utilisation within the muscle may still be limited. Adult muscle had the highest oxidative capacity, suggesting that fibres are able to effectively utilise available oxygen during prolonged dives. Elevated levels of total creatine in the muscles of juveniles may act as an energy buffer when fibres are transitioning from a fast to slow fibre type.

Gsα deficiency in skeletal muscle leads to reduced muscle mass, fiber-type switching, and glucose intolerance without insulin resistance or deficiency

The ubiquitously expressed G protein alpha-subunit G(s)alpha is required for receptor-stimulated intracellular cAMP responses and is an important regulator of energy and glucose metabolism. We have generated skeletal muscle-specific G(s)alpha-knockout (KO) mice (MGsKO) by mating G(s)alpha-floxed mice with muscle creatine kinase-cre transgenic mice. MGsKO mice had normal body weight and composition, and their serum glucose, insulin, free fatty acid, and triglyceride levels were similar to that of controls. However, MGsKO mice were glucose intolerant despite the fact that insulin sensitivity and glucose-stimulated insulin secretion were normal, suggesting an insulin-independent mechanism. Isolated muscles from MGsKO mice had increased basal glucose uptake and normal responses to a stimulator of AMP-activated protein kinase (AMPK), which indicates that AMPK and its downstream pathways are intact. Compared with control mice, MGsKO mice had reduced muscle mass with decreased cross-sectional area and force production. In addition, adult MGsKO mice showed an increased proportion of type I (slow-twitch, oxidative) fibers based on kinetic properties and myosin heavy chain isoforms, despite the fact that these muscles had reduced expression of peroxisome proliferator-activated receptor coactivator protein-1alpha (PGC-1alpha) and reduced mitochondrial content and oxidative capacity. Therefore G(s)alpha deficiency led to fast-to-slow fiber-type switching, which appeared to be dissociated from the expected change in oxidative capacity. MGsKO mice are a valuable model for future studies of the role of G(s)alpha signaling pathways in skeletal muscle adaptation and their effects on whole body metabolism.

Introduction to special section on ‘East Asia Climate and Environment’

Activities within the collaborative project East Asia Climate and Environment focus on the impact on the composition of chemically active greenhouse compounds from the rapidly growing emissions in Asia. Estimates of emissions (past and future) are discussed in light of the demand for energy in the different sectors. The impact includes regional scale contributions through short-lived climate compounds like particles and ozone, while global scale contributions are demonstrated through changes in oxidation capacity affecting compounds like CH4. One key issue is the important and increasing contribution from China to atmospheric chemical changes.