Increase In Muscle Oxidative Capacity Research Articles

Changes in Muscle Quality after Physical Rehabilitation Reduce Blood Pressure in Weightlifters with Arterial Hypertension: Randomized Controlled Trial

Hypertension is a frequent diagnosis in power athletes. Aim. To assess the effect of increased muscle oxidative capacity on blood pressure in athletes with arterial hypertension from power sports, heavy weight categories. Material and methods. The study was conducted at the Department of Sports Medicine of the Russian State University of Physical Culture, Sports, Youth and Tourism and lasted 180 days. The study involved 65 representatives of strength sports (weightlifting), heavy weight categories with arterial hypertension. Athletes were randomized into two main groups: the HIIT (High Intensity Interval Training, n=23) group, the MICE (Moderate Intensity Continuous Exercise, n=22) group and the RT (Resistance Training, n=20) control group. The following methods were used to achieve the aim of the study: ergospirometry, muscle tissue oxygenation level measurement, blood pressure measurement and methods of mathematical statistics. Athletes in the main groups trained for 180 days (3 times per week) on a cycle ergometer using a high-intensity interval and uniform protocol, and participants in the control group trained for 180 days (3 times per week) according to their traditional strength protocol. Results. After 180 days of physical rehabilitation, participants of the main groups had increased oxygen consumption at the anaerobic threshold, decreased thigh muscle oxygenation and increased maximum oxygen consumption, resulting in an average decrease in systolic blood pressure of 11.1 mm Hg and diastolic blood pressure of 11.2 mm Hg in the intervention groups. Conclusion. The physical rehabilitation systems we have developed for power athletes allow us to effectively and safely influence the oxidative capacity of working muscles and blood pressure, but the time spent by athletes on non-specific training activities in the HIIT system is 38% less.

Comparative transcriptomic and metabolomic analysis reveals pectoralis highland adaptation across altitudinal songbirds.

Pectoralis phenotypic variation plays a fundamental role in locomotion and thermogenesis in highland birds. However, its regulatory and metabolic mechanisms remain enigmatic to date. Here, we integrated phenomic, transcriptomic, and metabolomic approaches to determine muscle variation and its underpinning mechanisms across altitudinal songbirds. Phenomics confirmed that all highland birds had considerable increases in muscle oxidative capacity, capillarity, and mitochondrial abundance in our study. Correspondingly, transcriptomic analyses found that differentially expressed genes in phenotype-associated modules enriched for blood vessel, muscle structure development, and mitochondrial organization. Despite similar traits and functional enrichments across highland birds, different mechanisms drove their occurrence in high-altitude tree sparrow and 2 snow finches. Importantly, a metabolic feature shared by all the 3 highland birds is the improvement in insulin sensitivity and glucose utilization through activating insulin signaling pathway, which is vital to increase muscle oxidative capacity and maintain metabolic homeostasis. Nevertheless, fatty acid biosynthesis and oxidation are enhanced in only 2 snow finches which had a long evolutionary history on the high plateau, also differing from ketone body metabolism in recently introduced colonizer of the tree sparrow of the high plateau. Our study represents a vital contribution to reveal the regulatory and metabolic basis of pectoralis variation across altitudinal songbirds.

Endurance training-induced increase in muscle oxidative capacity without loss of muscle mass in younger and older resistance-trained men

While concurrent training is regularly used in older populations, the inverse relationship between fibre size and oxidative capacity suggests that endurance training in resistance-trained individuals may result in some loss of resistance training-induced gains in muscle mass, which may be more pronounced in older people. We investigated the impact of superimposed endurance training in younger (28.5 ± 4.8 years; n = 8) and older (67.5 ± 5.5 years; n = 7) highly resistance-trained men. Participants underwent a 10-week endurance cycling training programme consisting of five 6-min intervals at 75% max heart rate (HRmax) separated by 4-min intervals at 90% HRmax. The anatomical cross-sectional area (ACSA) of the thigh muscles, as determined with MRI, was 24% smaller in older compared to younger participants (p < 0.001). Although maximal oxygen consumption (VO2max) was also lower in the older group (p < 0.001), VO2max per kg body mass did not differ significantly between younger and older participants. Histological analyses of biopsies of the m. vastus lateralis showed that endurance training induced an increase in succinate dehydrogenase activity in both younger and older participants (p ≤ 0.043), and an increase in the number of capillaries around type I fibres (p = 0.017). The superimposed endurance training did not induce a significant decrease in thigh ACSA, fibre cross-sectional area, or knee extensor maximum voluntary isometric force. These observations indicate that adding endurance training to resistance training can lead to positive endurance-related adaptations without negative consequences for muscle size and strength in older and younger resistance-trained people.

Chronic cold exposure induces mitochondrial plasticity in deer mice native to high altitudes.

Small mammals native to high altitude must sustain high rates of thermogenesis to cope with cold. Skeletal muscle is a key site of shivering and non-shivering thermogenesis, but the importance of mitochondrial plasticity in cold hypoxic environments remains unresolved. We examined high-altitude deer mice, which have evolved a high capacity for aerobic thermogenesis, to determine the mechanisms of mitochondrial plasticity during chronic exposure to cold and hypoxia, alone and in combination. Cold exposure in normoxia or hypoxia increased mitochondrial leak respiration and decreased phosphorylation efficiency and OXPHOS coupling efficiency, which may serve to augment non-shivering thermogenesis. Cold also increased muscle oxidative capacity, but reduced the capacity for mitochondrial respiration via complex II relative to complexes I and II combined. High-altitude mice had a more oxidative muscle phenotype than low-altitude mice. Therefore, both plasticity and evolved changes in muscle mitochondria contribute to thermogenesis at high altitude. Small mammals native to high altitude must sustain high rates of thermogenesis to cope with cold and hypoxic environments. Skeletal muscle is a key site of shivering and non-shivering thermogenesis, but the importance of mitochondrial plasticity in small mammals at high altitude remains unresolved. High-altitude deer mice (Peromyscus maniculatus) and low-altitude white-footed mice (P. leucopus) were born and raised in captivity, and chronically exposed as adults to warm (25°C) normoxia, warm hypoxia (12kPa O2 ), cold (5°C) normoxia, or cold hypoxia. We then measured oxidative enzyme activities, oxidative fibre density and capillarity in the gastrocnemius, and used a comprehensive substrate titration protocol to examine the function of muscle mitochondria by high-resolution respirometry. Exposure to cold in both normoxia or hypoxia increased the activities of citrate synthase and cytochrome oxidase. In lowlanders, this was associated with increases in capillary density and the proportional abundance of oxidative muscle fibres, but in highlanders, these traits were unchanged at high levels across environments. Environment had some distinct effects on mitochondrial OXPHOS capacity between species, but the capacity of complex II relative to the combined capacity of complexes I and II was consistently reduced in both cold environments. Both cold environments also increased leak respiration and decreased phosphorylation efficiency and OXPHOS coupling efficiency in both species, which may serve to augment non-shivering thermogenesis. These cold-induced changes in mitochondrial function were overlaid upon the generally more oxidative phenotype of highlanders. Therefore, both plasticity and evolved changes in muscle mitochondria contribute to thermogenesis at high altitudes.

Speeding of oxygen uptake kinetics is not different following low-intensity blood-flow-restricted and high-intensity interval training.

What is the central question of this study? Can interval blood-flow-restricted (BFR) cycling training, undertaken at a low intensity, promote a similar adaptation to oxygen uptake ( ) kinetics to high-intensity interval training? What is the main finding and its importance? Speeding of pulmonary on-kinetics in healthy young subjects was not different between low-intensity interval BFR training and traditional high-intensity interval training. Given that very low workloads are well tolerated during BFR cycle training and speed on-kinetics, this training method could be used when high mechanical loads are contraindicated. Low-intensity blood-flow-restricted (BFR) endurance training is effective to increase aerobic capacity. Whether it speeds pulmonary oxygen uptake ( ), CO2 output ( ) and ventilatory ( ) kinetics has not been examined. We hypothesized that low-intensity BFR training would reduce the phase2 time constant (τp ) of , and by a similar magnitude to traditional high-intensity interval training (HIT). Low-intensity interval training with BFR served as a control. Twenty-four participants (25±6years old; maximal 46±6mlkg-1 min-1 ) were assigned to one of the following: low-intensity BFR interval training (BFR; n=8); low-intensity interval training without BFR (LOW; n=7); or high-intensity interval training without BFR (HIT; n=9). Training was 12 sessions of two sets of five to eight×2min cycling and 1min resting intervals. LOW and BFR were conducted at 30% of peak incremental power (Ppeak ), and HIT was at ∼103% Ppeak . For BFR, cuffs were inflated on both thighs (140-200mmHg) during exercise and deflated during rest intervals. Six moderate-intensity step transitions (30% Ppeak ) were averaged for analysis of pulmonary on-kinetics. Both BFR (pre- versus post-training τp =18.3±3.2 versus 14.5±3.4s; effect size=1.14) and HIT (τp =20.3±4.0 versus 13.1±2.9s; effect size=1.75) reduced the τp (P<0.05). As expected, there was no change in LOW ( τp =17.9±6.2 versus 17.7±4.3s; P=0.9). The kinetics of and were speeded only after HIT (38.5±10.6%, P<0.001 and 31.2±24.7%, P=0.004, respectively). Both HIT and low-intensity BFR training were effective in speeding moderate-intensity kinetics. These data support the findings of others that low-intensity cycling training with BFR increases muscle oxidative capacity.

Overreaching Attenuates Training-induced Improvements in Muscle Oxidative Capacity.

The aim of this study was to determine whether muscle oxidative capacity is influenced by alterations in training volume in middle-distance runners. Twenty-four highly trained middle-distance runners (n = 16 males; V˙O2peak = 73.3(4.3) mL·kg·min; n = 8 females, V˙O2peak = 63.2(3.4) mL·kg·min) completed 3 wk of normal training (NormTr), 3 wk of high-volume training (HVTr; a 10%, 20%, and 30% increase in training volume during each successive week from NormTr), and a 1-wk taper (TapTr; 55% exponential reduction in training volume from HVTr week 3). Before and immediately after each training period, the rate of recovery of muscle oxygen consumption (mV˙O2) of the gastrocnemius medialis was measured using near-infrared spectroscopy, with the rate constant indicating muscle oxidative capacity. Time to exhaustion (TTE) and V˙O2peak were determined during a maximal incremental treadmill test. Twelve subjects were classified as being functionally overreached (FOR) after HVTr (decreased running TTE and high perceived fatigue), whereas the other 12 subjects were classified as acutely fatigued (AF; no decrease in running TTE). The AF group demonstrated a significant increase in muscle oxidative capacity after HVTr (rate constant: 15.1% ± 9.7% min; P = 0.009), with no further improvement after TapTr, whereas there was no change in muscle oxidative capacity for FOR at any time point (P > 0.05). Compared with the FOR group, the AF group had substantially larger improvements in TTE from pre-HVTr to post-TapTr (FOR, 8.8% ± 3.7%; AF, 3.2% ± 3.0%; P = 0.04). The present study was able to demonstrate that muscle oxidative capacity was increased in response to a period of HVTr, but only in runners who did not develop FOR. Furthermore, runners who did not develop FOR had substantially larger performance improvements after a taper period.

Epigenetic and Metabolic Changes in Skeletal Muscle Underlying the Improvement of Insulin Sensitivity after Bariatric Surgery in Humans

Weight loss-induced improvement in insulin sensitivity (IS) has been related to enhanced muscle energy metabolism. Thus, we hypothesized that weight loss due to bariatric surgery may induce epigenomic changes, which in turn modify mitochondrial function and intracellular lipids. We previously reported that IS fails to improve at 2 weeks (2 w), but then continuously increases until 52 weeks (52 w) after surgery. Now, we monitored muscle mitochondrial function and lipid intermediates in 49 obese humans (OBE; 40±10 years, BMI 51±7 kg/m2) before and for 52 w after bariatric surgery. Genome-wide gene expression and DNA methylation were analyzed in a subgroup of 16 OBE. Initial weight loss increases muscle oxidative capacity by 11% at 2 w, but transient elevation of certain muscle diacylglycerols resulting from unrestrained adipose lipolysis prevents from rapid improvement in IS. At 52 w, both mitochondrial function and intracellular lipids are comparable to lean humans. Acute alterations in expression of 1287 genes involved primarily in mitochondrial function, transcriptional regulation, protein transport, fatty acid metabolism and inflammatory processes, but not changes in DNA methylation, underlie the transient upregulation of mitochondrial function and lipolysis. At 52 w, 1091CpGs are differentially methylated, which relates to improved IS. Specifically, epigenetic alterations at 52 w in FTO gene, encoding an α-ketoglutarate dependent dioxygenase, and TOMM7 gene, encoding a translocase of the outer mitochondrial membrane, contribute to reprogramming transient changes in mRNA expression at 2 w. In conclusion, initial metabolic changes after weight loss induce epigenetic modification of genes involved in muscle energy metabolism, which in turn leads to long-term beneficial changes in gene expression. Disclosure S. Gancheva: None. M. Ouni: None. C. Koliaki: None. T. Jelenik: None. D.F. Markgraf: None. J. Szendroedi: None. M. Schlensak: None. A. Schuermann: None. M. Roden: Speaker's Bureau; Self; Boehringer Ingelheim GmbH. Research Support; Self; Boehringer Ingelheim GmbH. Consultant; Self; Poxel SA. Research Support; Self; Danone Nutricia Early Life Nutrition, GlaxoSmithKline plc., Nutricia Advanced Medical Nutrition, Sanofi.

The role of androgens in the regulation of muscle oxidative capacity following aerobic exercise training.

Reduced production or bioavailability of androgens, termed hypogonadism, occurs in a variety of pathological conditions. While androgens target numerous tissues throughout the body, hypogonadism specifically reduces the ability of skeletal muscle to produce adenosine triphosphate aerobically, i.e., muscle oxidative capacity. This has important implications for overall health as muscle oxidative capacity impacts a number of metabolic processes. Although androgen replacement therapy is effective at restoring muscle oxidative capacity in hypogonadal individuals, this is not a viable therapeutic option for all who are experiencing hypogonadism. While aerobic exercise may be a viable alternative to increase muscle oxidative capacity, it is unknown whether androgen depletion affects this adaptation. To determine this, sham and castrated mice were randomized to remain sedentary or undergo 8 weeks of aerobic treadmill exercise training. All mice were fasted overnight prior to sacrifice. Though exercise increased markers of muscle oxidative capacity independent of castration (cytochrome c oxidase subunit IV and cytochrome c), these measures were lower in castrated mice. This reduction was not due to a difference in peroxisome proliferator activated receptor gamma coactivator 1 alpha protein content, as expression was increased to a similar absolute value in sham and castrated animals following exercise training. However, markers of BCL2/Adenovirus E1B 19 kDa Interacting Protein 3 (BNIP3)-mediated mitophagy were increased by castration independent of exercise. Together, these data show that exercise training can increase markers of muscle oxidative capacity following androgen depletion. However, these values are reduced by androgen depletion likely due in part to elevated BNIP3-mediated mitophagy.

Effect of Exercise Training on Signaling of Interleukin-6 in Skeletal Muscles of Type 2 Diabetic Rats.

Diabetes and exercise training have been shown to involve interleukin 6 (IL-6) signaling in muscle. However, the relationship between the actions of these two stimuli on muscle IL-6 and their downstream components is still unknown. Thus, the effect of endurance training on the key components of muscle IL-6 signaling transduction was investigated in a rat model of type 2 diabetes. Diabetes was induced by streptozotocin (STZ) in male Wistar rats fed a high-fat diet, with normal rats acting as controls. The animals were left to conduct their normal activities or assigned to endurance training in a treadmill. At the end of 8 weeks, blood biochemical profiles, exercise performance, muscle oxidative capacity, glucose transporter 4 (GLUT4) protein distribution, and expressions of IL-6 and its downstream proteins were determined. Blood biochemical profiles of the diabetic rats were altered compared to normal rats, whereas endurance training improved blood chemistry and exercise performance. It also increased muscle oxidative capacity, and promoted GLUT4 subcellular localization to the membrane in muscles. Furthermore, protein expression of IL-6 receptor (IL-6Rα) was increased in both normal and diabetic rats after endurance training, but no significant changes in IL-6, phosphorylated signal transducer and activator of transcription 3 (p-STAT3), or suppressor of cytokine signaling 3 (SOC3) were observed in muscles of normal and diabetic rats. IL-6 signaling pathway mediating muscle response to endurance training was conserved in type 2 diabetes. There was no link between training-induced IL-6 downstream targets in skeletal muscles and IL-6-induced type 2 diabetes.

Combination of exercise training and erythropoietin prevents cancer-induced muscle alterations.

Cancer cachexia is a syndrome characterized by loss of skeletal muscle mass, inflammation, anorexia and anemia, contributing to patient fatigue and reduced quality of life. In addition to nutritional approaches, exercise training (EX) has been proposed as a suitable tool to manage cachexia. In the present work the effect of mild exercise training, coupled to erythropoietin (EPO) administration to prevent anemia, has been tested in tumor-bearing mice. In the C26 hosts, acute exercise does not prevent and even worsens muscle wasting. Such pattern is prevented by EPO co-administration or by the adoption of a chronic exercise protocol. EX and EPO co-treatment spares oxidative myofibers from atrophy and counteracts the oxidative to glycolytic shift, inducing PGC-1α. LLC hosts are responsive to exercise and their treatment with the EX-EPO combination prevents the loss of muscle strength and the onset of mitochondrial ultrastructural alterations, while increases muscle oxidative capacity and intracellular ATP content, likely depending on PGC-1α induction and mitophagy promotion. Consistently, muscle-specific PGC-1α overexpression prevents LLC-induced muscle atrophy and Atrogin-1 hyperexpression. Overall, the present data suggest that low intensisty exercise can be an effective tool to be included in combined therapeutic approaches against cancer cachexia, provided that anemia is coincidently treated in order to enhance the beneficial action of exercise.

Carnitine supplementation in high-fat diet-fed rats does not ameliorate lipid-induced skeletal muscle mitochondrial dysfunction in vivo.

Muscle lipid overload and the associated accumulation of lipid intermediates play an important role in the development of insulin resistance. Carnitine insufficiency is a common feature of insulin-resistant states and might lead to incomplete fatty acid oxidation and impaired export of lipid intermediates out of the mitochondria. The aim of the present study was to test the hypothesis that carnitine supplementation reduces high-fat diet-induced lipotoxicity, improves muscle mitochondrial function, and ameliorates insulin resistance. Wistar rats were fed either normal chow or a high-fat diet for 15 wk. One group of high-fat diet-fed rats was supplemented with 300 mg·kg(-1)·day(-1) L-carnitine during the last 8 wk. Muscle mitochondrial function was measured in vivo by (31)P magnetic resonance spectroscopy (MRS) and ex vivo by high-resolution respirometry. Muscle lipid status was determined by (1)H MRS (intramyocellular lipids) and tandem mass spectrometry (acylcarnitines). High-fat diet feeding induced insulin resistance and was associated with decreases in muscle and blood free carnitine, elevated levels of muscle lipids and acylcarnitines, and an increased number of muscle mitochondria that showed an improved capacity to oxidize fat-derived substrates when tested ex vivo. This was, however, not accompanied by an increase in muscle oxidative capacity in vivo, indicating that in vivo mitochondrial function was compromised. Despite partial normalization of muscle and blood free carnitine content, carnitine supplementation did not induce improvements in muscle lipid status, in vivo mitochondrial function, or insulin sensitivity. Carnitine insufficiency, therefore, does not play a major role in high-fat diet-induced muscle mitochondrial dysfunction in vivo.

Vitamin E supplementation modifies adaptive responses to training in rat skeletal muscle

Aim of the present study was to test, by vitamin E treatment, the hypothesis that muscle adaptive responses to training are mediated by free radicals produced during the single exercise sessions. Therefore, we determined aerobic capacity of tissue homogenates and mitochondrial fractions, tissue content of mitochondrial proteins and expression of factors (PGC-1, NRF-1, and NRF-2) involved in mitochondrial biogenesis. Moreover, we determined the oxidative damage extent, antioxidant enzyme activities, and glutathione content in both tissue preparations, mitochondrial ROS production rate. Finally we tested mitochondrial ROS production rate and muscle susceptibility to oxidative stress. The metabolic adaptations to training, consisting in increased muscle oxidative capacity coupled with the proliferation of a mitochondrial population with decreased oxidative capacity, were generally prevented by antioxidant supplementation. Accordingly, the expression of the factors involved in mitochondrial biogenesis, which were increased by training, was restored to the control level by the antioxidant treatment. Even the training-induced increase in antioxidant enzyme activities, glutathione level and tissue capacity to oppose to an oxidative attach were prevented by vitamin E treatment. Our results support the idea that the stimulus for training-induced adaptive responses derives from the increased production, during the training sessions, of reactive oxygen species that stimulates the expression of PGC-1, which is involved in mitochondrial biogenesis and antioxidant enzymes expression. On the other hand, the observation that changes induced by training in some parameters are only attenuated by vitamin E treatment suggests that other signaling pathways, which are activated during exercise and impinge on PGC-1, can modify the response to the antioxidant integration.

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.

Effect of eccentric training on mitochondrial function and oxidative stress in the skeletal muscle of rats

The objective of the present study was to investigate the effects of eccentric training on the activity of mitochondrial respiratory chain enzymes, oxidative stress, muscle damage, and inflammation of skeletal muscle. Eighteen male mice (CF1) weighing 30-35 g were randomly divided into 3 groups (N = 6): untrained, trained eccentric running (16°; TER), and trained running (0°) (TR), and were submitted to an 8-week training program. TER increased muscle oxidative capacity (succinate dehydrogenase and complexes I and II) in a manner similar to TR, and TER did not decrease oxidative damage (xylenol and creatine phosphate) but increased antioxidant enzyme activity (superoxide dismutase and catalase) similar to TR. Muscle damage (creatine kinase) and inflammation (myeloperoxidase) were not reduced by TER. In conclusion, we suggest that TER improves mitochondrial function but does not reduce oxidative stress, muscle damage, or inflammation induced by eccentric contractions.

Effect of eccentric training on mitochondrial function and oxidative stress in the skeletal muscle of rats

The objective of the present study was to investigate the effects of eccentric training on the activity of mitochondrial respiratory chain enzymes, oxidative stress, muscle damage, and inflammation of skeletal muscle. Eighteen male mice (CF1) weighing 30-35 g were randomly divided into 3 groups (N = 6): untrained, trained eccentric running (16°; TER), and trained running (0°) (TR), and were submitted to an 8-week training program. TER increased muscle oxidative capacity (succinate dehydrogenase and complexes I and II) in a manner similar to TR, and TER did not decrease oxidative damage (xylenol and creatine phosphate) but increased antioxidant enzyme activity (superoxide dismutase and catalase) similar to TR. Muscle damage (creatine kinase) and inflammation (myeloperoxidase) were not reduced by TER. In conclusion, we suggest that TER improves mitochondrial function but does not reduce oxidative stress, muscle damage, or inflammation induced by eccentric contractions.

High-intensity interval training increases in vivo oxidative capacity with no effect on Pi→ATP rate in resting human muscle

Mitochondrial ATP production is vital for meeting cellular energy demand at rest and during periods of high ATP turnover. We hypothesized that high-intensity interval training (HIT) would increase ATP flux in resting muscle (VPi→ATP) in response to a single bout of exercise, whereas changes in the capacity for oxidative ATP production (Vmax) would require repeated bouts. Eight untrained men (27 ± 4 yr; peak oxygen uptake = 36 ± 4 ml·kg(-1)·min(-1)) performed six sessions of HIT (4-6 × 30-s bouts of all-out cycling with 4-min recovery). After standardized meals and a 10-h fast, VPi→ATP and Vmax of the vastus lateralis muscle were measured using phosphorus magnetic resonance spectroscopy at 4 Tesla. Measurements were obtained at baseline, 15 h after the first training session, and 15 h after completion of the sixth session. VPi→ATP was determined from the unidirectional flux between Pi and ATP, using the saturation transfer technique. The rate of phosphocreatine recovery (kPCr) following a maximal contraction was used to calculate Vmax. While kPCr and Vmax were unchanged after a single session of HIT, completion of six training sessions resulted in a ∼14% increase in muscle oxidative capacity (P ≤ 0.004). In contrast, neither a single nor six training sessions altered VPi→ATP (P = 0.74). This novel analysis of resting and maximal high-energy phosphate kinetics in vivo in response to HIT provides evidence that distinct aspects of human skeletal muscle metabolism respond differently to this type of training.

TRPV4 deficiency increases skeletal muscle metabolic capacity and resistance against diet-induced obesity

Transient receptor potential channel V4 (TRPV4) functions as a nonselective cation channel in various cells and plays physiological roles in osmotic and thermal sensation. However, the function of TRPV4 in energy metabolism is unknown. Here, we report that TRPV4 deficiency results in increased muscle oxidative capacity and resistance to diet-induced obesity in mice. Although no difference in body weight was observed between wild-type and Trpv4(-/-) mice when fed a standard chow diet, obesity phenotypes induced by a high-fat diet were significantly improved in Trpv4(-/-) mice, without any change in food intake. Quantitative analysis of mRNA revealed the constitutive upregulation of many genes, including those for transcription factors such as peroxisome proliferator-activated receptor α and for metabolic enzymes such as phosphoenolpyruvate carboxykinase. These upregulated genes were especially prominent in oxidative skeletal muscle, in which the activity of Ca(2+)-dependent phosphatase calcineurin was elevated, suggesting that other Ca(2+) channels function in the skeletal muscle of Trpv4(-/-) mice. Indeed, gene expressions for TRPC3 and TRPC6 increased in the muscles of Trpv4(-/-) mice compared with those of wild-type mice. The number of oxidative type I fiber also increased in the mutant muscles following myogenin gene induction. These results strongly suggested that inactivation of Trpv4 induces compensatory increases in TRPC3 and TRPC6 production, and elevation of calcineurin activity, affecting energy metabolism through increased expression of genes involved in fuel oxidation in skeletal muscle and thereby contributing to increased energy expenditure and protection from diet-induced obesity in mice.

Chronic cold acclimation increases thermogenic capacity, non-shivering thermogenesis and muscle citrate synthase activity in both wild-type and brown adipose tissue deficient mice

The purpose of this study was to determine whether chronic cold exposure would increase the aerobic capacity of skeletal muscle in UCP-dta mice, a transgenic line lacking brown adipose tissue (BAT). Wild type and UCP-dta mice were acclimated to either warm (23°C), or cold (4°C) conditions. Cold increased muscle oxidative capacity nearly equivalently in wild-type and UCP-dta mice, but did not affect the respiratory function of isolated mitochondria. Summit metabolism (V˙O2summit) and norepinephrine-induced thermogenesis (V˙O2NST) were significantly lower in UCP-dta mice relative to wild-type mice regardless of temperature treatment, but both were significantly higher in cold relative to warm acclimated mice. BAT mass was significantly higher in the cold relative to warm acclimated wild-type mice, but not in cold acclimated UCP-dta mice. BAT citrate synthase activity was lower in transgenic animals regardless of acclimation temperature and BAT citrate synthase activity per depot was significantly higher only in the cold acclimated wild-type mice. Muscle citrate synthase activity was increased in both genotypes. As defects in muscle oxidative function have been observed with obesity and type 2 diabetes, these results suggest that chronic cold exposure is a useful intervention to drive skeletal muscle oxidative capacity in mouse models of obesity.

Effect of sprint interval training on circulatory function during exercise in sedentary, overweight/obese women

Very high-intensity, low-volume, sprint interval training (SIT) increases muscle oxidative capacity and may increase maximal oxygen uptake ([Formula: see text]), but whether circulatory function is improved, and whether SIT is feasible in overweight/obese women is unknown. To examine the effects of SIT on [Formula: see text] and circulatory function in sedentary, overweight/obese women. Twenty-eight women with BMI>25 were randomly assigned to SIT or control (CON) groups. One week before pre-testing, subjects were familarized to [Formula: see text] testing and the workload that elicited 50% [Formula: see text] was calculated. Pre- and post-intervention, circulatory function was measured at 50% of the pre-intervention [Formula: see text], and a GXT was performed to determine [Formula: see text]. During the intervention, SIT training was given for 3days/week for 4weeks. Training consisted of 4-7, 30-s sprints on a stationary cycle (5% body mass as resistance) with 4min active recovery between sprints. CON maintained baseline physical activity. Post-intervention, heart rate (HR) was significantly lower and stroke volume (SV) significantly higher in SIT (-8.1 and 11.4%, respectively; P<0.05) during cycling at 50% [Formula: see text]; changes in CON were not significant (3 and -4%, respectively). Changes in cardiac output ([Formula: see text]) and arteriovenous oxygen content difference [(a-v)O(2) diff] were not significantly different for SIT or CON. The increase in [Formula: see text] by SIT was significantly greater than by CON (12 vs. -1%). Changes by SIT and CON in HR(max) (-1 vs. -1%) were not significantly different. Four weeks of SIT improve circulatory function during submaximal exercise and increases [Formula: see text] in sedentary, overweight/obese women.

A Single ∼4 Min Bout Of All-out Exercise Augments PGC-1α mRNA Expression In Human Skeletal Muscle

High-intensity interval training (HIT) performed at an "all-out" intensity is a potent stimulus for mitochondrial biogenesis in human skeletal muscle (Gibala et al. J Physiol. 575: 901-911, 2006). Six sessions of HIT over 2 wk (4-6 maximal 30 s cycle sprints with 4 min of recovery per session) increased mitochondrial enzyme activity to the same extent as traditional endurance training (90-120 min of moderate-intensity cycling per session). These HIT-induced adaptations appear linked to repeated transient increases in the transcriptional coactivator PGC-1α (Gibala et al. J Appl Physiol. 106: 929-934, 2009). Thus, a few minutes of very high intensity exercise performed in an intermittent fashion, and interspersed with brief rest/recovery periods is sufficient to increases PGC-1α(acutely) and muscle oxidative capacity (chronically) in human skeletal muscle. However the relative importance of the "pulsed" nature of the HIT stimulus remains unclear. PURPOSE: To determine whether a single bout of all out exercise would stimulate an increase in PGC-1αmRNA expression similar to an intermittent maximal cycling protocol matched for total work output. METHODS: Eight men (22±1 y, 48±2 mL·kg−1·min−1) performed two exercise trials in random order ≥1 wk apart. During one session, subjects performed 4 × 30 s all out sprints separated by 4 min of rest (HIT). In the other trial, subjects performed an isovolumetric amount of work (67.0±2.4 kJ; IsoV) as the HIT trial, but in a single continuous all-out effort. RESULTS: Mean power averaged over the 4 sprints was 557±16 W, whereas mean power during the single bout was 287±18 W. Thus, mean time to completion in IsoV was ∼4 min (3:58±0:09 min:s; range: 3:23-4:30 min:s), near double that of the 4 × 30 s HIT trial (excluding recovery, p<0.05). However, when HIT recovery was included, total time commitment of the IsoV trial was only ∼30% of HIT. RT-PCR analysis of skeletal muscle biopsies revealed a similar ∼3.1-fold increase in PGC-1αmRNA 3 h post-exercise compared to pre-exercise, with no differences between trials (p<0.05, main effect for time). CONCLUSIONS: These findings indicate that augmentations in PGC-1αmRNA expression are achieved by very low volumes of all-out exercise whether performed continuously or intermittently. It appears that as little as 3-5 min of all out continuous exercise may be sufficient to stimulate mitochondrial biogenesis in human skeletal muscle. Supported by NSERC.