Skeletal Muscle Oxidative Metabolism Research Articles

Noninvasive estimation of skeletal muscle oxygen consumption rate and microvascular reactivity in chronic stroke survivors using near-infrared spectroscopy.

Understanding post-stroke changes in skeletal muscle oxidative metabolism and microvascular reactivity could help create therapeutic targets that optimize rehabilitative interventions. Due to disuse atrophy, we hypothesized that basal muscle oxygen consumption rate and microvascular endothelial function would be impaired in the tibialis anterior (TA) muscle of the affected leg of chronic stroke survivors compared with the nonaffected leg and versus matched controls. Fifteen chronic stroke survivors (10 females) and 15 matched controls (9 females) completed this study. A near-infrared spectroscopy oximeter measured tissue oxygen saturation (StO2) of the TA in both legs of stroke survivors and the dominant leg of controls. A cuff was placed around the thigh and inflated to 225 mmHg for 5 min while StO2 was continuously measured. The rate of change in StO2 was calculated during cuff occlusion and immediately post-cuff release. The rate of oxygen desaturation was similar between the legs of the stroke survivors (paretic -0.12 ± 0.04%·s-1 vs. nonparetic -0.16 ± 011%·s-1; P = 0.49), but the paretic leg had a reduced desaturation rate versus controls (-0.25 ± 0.18%·s-1; P = 0.007 vs. paretic leg). After cuff release, there was a greater oxygen resaturation rate in the nonparetic leg compared with the paretic leg (3.13 ± 2.08%·s-1 vs. 1.60 ± 1.11%·s-1, respectively; P = 0.01). The control leg had a similar resaturation rate versus the nonparetic leg (control = 3.41 ± 1.79%·s-1; P = 0.69) but was greater than the paretic leg (P = 0.003). The TA in the paretic leg had an impaired muscle oxygen consumption rate and reduced microvascular endothelial function compared with controls.NEW & NOTEWORTHY Secondary consequences of stroke are not well described. In this study, we show that basal muscle oxidative consumption and microvascular endothelial function are reduced in the paretic tibialis anterior muscle of chronic stroke survivors compared with matched controls using near-infrared spectroscopy and the vascular occlusion technique. There was a moderately strong correlation between microvascular endothelial function and paretic leg strength.

Class IIa HDACs inhibit cell death pathways and protect muscle integrity in response to lipotoxicity

Lipotoxicity, the accumulation of lipids in non-adipose tissues, alters the metabolic transcriptome and mitochondrial metabolism in skeletal muscle. The mechanisms involved remain poorly understood. Here we show that lipotoxicity increased histone deacetylase 4 (HDAC4) and histone deacetylase 5 (HDAC5), which reduced the expression of metabolic genes and oxidative metabolism in skeletal muscle, resulting in increased non-oxidative glucose metabolism. This metabolic reprogramming was also associated with impaired apoptosis and ferroptosis responses, and preserved muscle cell viability in response to lipotoxicity. Mechanistically, increased HDAC4 and 5 decreased acetylation of p53 at K120, a modification required for transcriptional activation of apoptosis. Redox drivers of ferroptosis derived from oxidative metabolism were also reduced. The relevance of this pathway was demonstrated by overexpression of loss-of-function HDAC4 and HDAC5 mutants in skeletal muscle of obese db/db mice, which enhanced oxidative metabolic capacity, increased apoptosis and ferroptosis and reduced muscle mass. This study identifies HDAC4 and HDAC5 as repressors of skeletal muscle oxidative metabolism, which is linked to inhibition of cell death pathways and preservation of muscle integrity in response to lipotoxicity.

Impact of aerobic fitness status, menstrual cycle phase, and oral contraceptive use on exercise substrate oxidation and metabolic flexibility in females.

The influence of menstrual cycle phase and fitness status on metabolism during high-intensity interval exercise (HIIE) was assessed. Twenty-five females (24.4 (3.6) years) were categorized by normal menstrual cycle (n=14) vs. oral contraceptive (OC) use (n=11) and by aerobic fitness, high-fitness females (HFF; n=13) vs. low-fitness females (LFF; n=12). HIIE was four sets of four repetitions with a 3min rest between intervals on a cycle ergometer at a power output halfway between the ventilatory threshold and V̇O2peak and performed during follicular (FOL: days 2-7 or inactive pills) and luteal phases (LUT: day ∼21 or 3rd week of active pills). Substrate oxidation was assessed via indirect calorimetry, blood lactate via finger stick, and recovery of skeletal muscle oxidative metabolism (mV̇O2) via continuous-wave near-infrared spectroscopy. HFF oxidized more fat (g·kg-1) during the full session (FOL: p=0.050, LUT: p=0.001), high intervals (FOL: p=0.048, LUT: p=0.001), low intervals (FOL: p=0.032, LUT: p=0.024), and LUT recovery (p=0.033). Carbohydrate oxidation area under the curve was greater in HFF during FOL (FOL: p=0.049, LUT: p=0.124). Blood lactate was lower in LFF in FOL (p≤0.05) but not in LUT. Metabolic flexibility (Δ fat oxidation g·kg-1·min-1) was greater in HFF than LFF during intervals 2-3 in FOL and 1-4 in LUT (p≤0.05). Fitness status more positively influences exercise metabolic flexibility during HIIE than cycle phase or OC use.

Loss of skeletal muscle estrogen-related receptors leads to severe exercise intolerance

ObjectiveSkeletal muscle oxidative capacity is central to physical activity, exercise capacity and whole-body metabolism. The three estrogen-related receptors (ERRs) are regulators of oxidative metabolism in many cell types, yet their roles in skeletal muscle remain unclear. The main aim of this study was to compare the relative contributions of ERRs to oxidative capacity in glycolytic and oxidative muscle, and to determine defects associated with loss of skeletal muscle ERR function. MethodsWe assessed ERR expression, generated mice lacking one or two ERRs specifically in skeletal muscle and compared the effects of ERR loss on the transcriptomes of EDL (predominantly glycolytic) and soleus (oxidative) muscles. We also determined the consequences of the loss of ERRs for exercise capacity and energy metabolism in mice with the most severe loss of ERR activity. ResultsERRs were induced in human skeletal muscle in response to an exercise bout. Mice lacking both ERRα and ERRγ (ERRα/γ dmKO) had the broadest and most dramatic disruption in skeletal muscle gene expression. The most affected pathway was “mitochondrial function”, in particular Oxphos and TCA cycle genes, and transcriptional defects were more pronounced in the glycolytic EDL than the oxidative soleus. Mice lacking ERRβ and ERRγ, the two isoforms expressed highly in oxidative muscles, also exhibited defects in lipid and branch chain amino acid metabolism genes, specifically in the soleus. The pronounced disruption of oxidative metabolism in ERRα/γ dmKO mice led to pale muscles, decreased oxidative capacity, histochemical patterns reminiscent of minicore myopathies, and severe exercise intolerance, with the dmKO mice unable to switch to lipid utilization upon running. ERRα/γ dmKO mice showed no defects in whole-body glucose and energy homeostasis. ConclusionsOur findings define gene expression programs in skeletal muscle that depend on different combinations of ERRs, and establish a central role for ERRs in skeletal muscle oxidative metabolism and exercise capacity. Our data reveal a high degree of functional redundancy among muscle ERR isoforms for the protection of oxidative capacity, and show that ERR isoform-specific phenotypes are driven in part, but not exclusively, by their relative levels in different muscles.

Acute resistance exercise training does not augment mitochondrial remodelling in master athletes or untrained older adults.

Background: Ageing is associated with alterations to skeletal muscle oxidative metabolism that may be influenced by physical activity status, although the mechanisms underlying these changes have not been unraveled. Similarly, the effect of resistance exercise training (RET) on skeletal muscle mitochondrial regulation is unclear. Methods: Seven endurance-trained masters athletes ([MA], 74 ± 3years) and seven untrained older adults ([OC]. 69 ± 6years) completed a single session of knee extension RET (6 x 12 repetitions, 75% 1-RM, 120-s intra-set recovery). Vastus lateralis muscle biopsies were collected pre-RET, 1h post-RET, and 48h post-RET. Skeletal muscle biopsies were analyzed for citrate synthase (CS) enzyme activity, mitochondrial content, and markers of mitochondrial quality control via immunoblotting. Results: Pre-RET CS activity and protein content were ∼45% (p < .001) and ∼74% greater in MA compared with OC (p = .006). There was a significant reduction (∼18%) in CS activity 48h post-RET (p < .05) in OC, but not MA. Pre-RET abundance of individual and combined mitochondrial electron transport chain (ETC) complexes I-V were significantly greater in MA compared with OC, as were markers of mitochondrial fission and fusion dynamics (p-DRP-1Ser616, p-MFFSer146, OPA-1 & FIS-1, p < .05 for all). Moreover, MA displayed greater expression of p-AMPKThr172, PGC1α, TFAM, and SIRT-3 (p < .05 for all). Notably, RET did not alter the expression of any marker of mitochondrial content, biogenesis, or quality control in both OC and MA. Conclusion: The present data suggest that long-term aerobic exercise training supports superior skeletal muscle mitochondrial density and protein content into later life, which may be regulated by greater mitochondrial quality control mechanisms and supported via superior fission-fusion dynamics. However, a single session of RET is unable to induce mitochondrial remodelling in the acute (1h post-RET) and delayed (48h post-RET) recovery period in OC and MA.

Nicotinamide Riboside Supplementation to Suckling Male Mice Improves Lipid and Energy Metabolism in Skeletal Muscle and Liver in Adulthood.

Nicotinamide riboside, an NAD+ precursor, has been attracting a lot of attention in recent years due to its potential benefits against multiple metabolic complications and age-related disorders related to NAD+ decline in tissues. The metabolic programming activity of NR supplementation in early-life stages is much less known. Here, we studied the long-term programming effects of mild NR supplementation during the suckling period on lipid and oxidative metabolism in skeletal muscle and liver tissues using an animal model. Suckling male mice received a daily oral dose of NR or vehicle (water) from day 2 to 20 of age, were weaned at day 21 onto a chow diet, and at day 90 were distributed to either a high-fat diet (HFD) or a normal-fat diet for 10 weeks. Compared to controls, NR-treated mice were protected against HFD-induced triacylglycerol accumulation in skeletal muscle and displayed lower triacylglycerol levels and steatosis degree in the liver and distinct capacities for fat oxidation and decreased lipogenesis in both tissues, paralleling signs of enhanced sirtuin 1 and AMP-dependent protein kinase signaling. These pre-clinical findings suggest that mild NR supplementation in early postnatal life beneficially impacts lipid and energy metabolism in skeletal muscle and liver in adulthood, serving as a potential preventive strategy against obesity-related disorders characterized by ectopic lipid accumulation.

Natriuretic peptides control of skeletal muscle oxidative metabolism

Besides their well-known effect in the regulation of blood volume, natriuretic peptides have emerged during the last two decades as key metabolic hormones linking cardiac function to energy metabolism. Recent work from our laboratory underscores a new role of these peptides in the control of oxidative metabolism in skeletal muscle and open novel perspectives in the field of chronic diseases affecting skeletal muscles.

In vivo assessment of OXPHOS capacity using 3\xa0T CrCEST MRI in Friedreich\u2019s ataxia

BackgroundFriedreich’s ataxia (FRDA) is a neurodegenerative disease caused by decreased expression of frataxin, a protein involved in many cellular metabolic processes, including mitochondrial oxidative phosphorylation (OXPHOS). Our objective was to assess skeletal muscle oxidative metabolism in vivo in adults with FRDA as compared to adults without FRDA using chemical exchange saturation transfer (CrCEST) MRI, which measures free creatine (Cr) over time following an in-magnet plantar flexion exercise.MethodsParticipants included adults with FRDA (n = 11) and healthy adults (n = 25). All underwent 3-Tesla CrCEST MRI of the calf before and after in-scanner plantar flexion exercise. Participants also underwent whole-body dual-energy X-ray absorptiometry (DXA) scans to measure body composition and completed questionnaires to assess physical activity.ResultsWe found prolonged post-exercise exponential decline in CrCEST (τCr) in the lateral gastrocnemius (LG, 274 s vs. 138 s, p = 0.01) in adults with FRDA (vs. healthy adults), likely reflecting decreased OXPHOS capacity. Adults with FRDA (vs. healthy adults) also engaged different muscle groups during exercise, as indicated by muscle group-specific changes in creatine with exercise (∆CrCEST), possibly reflecting decreased coordination. Across all participants, increased adiposity and decreased usual physical activity were associated with smaller ∆CrCEST.ConclusionIn FRDA, CrCEST MRI may be a useful biomarker of muscle-group-specific decline in OXPHOS capacity that can be leveraged to track within-participant changes over time. Appropriate participant selection and further optimization of the exercise stimulus will enhance the utility of this technique.

Muscle-secreted neurturin couples myofiber oxidative metabolism and slow motor neuron identity

Endurance exercise promotes skeletal muscle vascularization, oxidative metabolism, fiber-type switching, and neuromuscular junction integrity. Importantly, the metabolic and contractile properties of the muscle fiber must be coupled to the identity of the innervating motor neuron (MN). Here, we show that muscle-derived neurturin (NRTN) acts on muscle fibers and MNs to couple their characteristics. Using a muscle-specific NRTN transgenic mouse (HSA-NRTN) and RNA sequencing of MN somas, we observed that retrograde NRTN signaling promotes a shift toward a slow MN identity. In muscle, NRTN increased capillary density and oxidative capacity and induced a transcriptional reprograming favoring fatty acid metabolism over glycolysis. This combination of effects on muscle and MNs makes HSA-NRTN mice lean with remarkable exercise performance and motor coordination. Interestingly, HSA-NRTN mice largely recapitulate the phenotype of mice with muscle-specific expression of its upstream regulator PGC-1ɑ1. This work identifies NRTN as a myokine that couples muscle oxidative capacity to slow MN identity.

Low‐dose lithium supplementation augments mitochondrial biogenesis in murine skeletal muscle after high fat feeding

Promotion of oxidative metabolism in skeletal muscle improves muscle performance, fatigue resistance, and may help combat the obesogenic effects of a high fat diet. Lithium is a well-known glycogen synthase kinase (GSK3) inhibitor and we have recently shown that low-dose lithium supplementation (10 mg kg-1 day-1) augments skeletal muscle oxidative capacity in mice. In the soleus muscle, lithium mediated GSK3 inhibition increased the expression of oxidative markers such as peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1a) and myosin heavy chain I (MHCI) leading to improvements in muscle contractility and fatigue resistance. Interestingly, this same dose of lithium (10 mg kg-1 day-1) has been previously shown to attenuate high fat diet induced weight gain and metabolic efficiency (weight gained per calories consumed). However, the impact of lithium supplementation on muscle oxidative phenotype after high fat feeding has yet to be investigated. In this study, 36 wild-type male C57BL/6J mice were randomly assigned to low-fat standard chow diet (LFD, 4% kcal fat), high-fat diet (HFD, 60% kcal fat), or HFD with lithium chloride (HFD + Li; 10 mg kg-1 day-1) treatment groups for 12 weeks. Soleus muscles were collected at the end for Western blot analysis of total and phosphorylated GSK3 (inhibitory sites serine9 for GSK3b and serine21 for GSK3a), PGC-1a, cytochrome c oxidase subunit IV (COXIV), and MHCI protein content. Our results showed that the level of phosphorylated GSK3a and GSK3b (relative to total GSK3) were significantly lower after the HFD (-41 and -44%, respectively, p < 0.05), but in the HFD + Li group levels were similar to the LFD group. Therefore, the HFD enhanced soleus muscle GSK3 activation, and lithium supplementation was able to reduce this effect. No significant changes in MHCI content were observed. When examining PGC-1a, we found that the HFD + Li group had protein levels that were nearly 2-fold higher vs LFD, albeit only trending towards significance (p = 0.06). Further, COXIV content progressively increased from LFD, to HFD, and to HFD + Li (linear trend, r2=0.26, p = 0.002) with both HFD and HFD + Li groups having significantly higher COXIV content when compared to LFD. Altogether, our data shows that GSK3 inhibition via low dose lithium supplementation can augment mitochondrial biogenesis in the presence of a HFD. Future studies will further examine whether GSK3 inhibition via lithium can augment muscle oxidative metabolism after high fat feeding.

Dynamic 31P-MRI and 31P-MRS of lower leg muscles in heart failure patients

Impaired oxidative metabolism is one of multi-variate factors leading to exercise intolerance in heart failure patients. The purpose of the study was to demonstrate the use of dynamic 31P magnetic resonance spectroscopy (MRS) and 31P magnetic resonance imaging (MRI) techniques to measure PCr resynthesis rate post-exercise as a biomarker for oxidative metabolism in skeletal muscle in HF patients and controls. In this prospective imaging study, we recruited six HF patients and five healthy controls. The imaging protocol included 31P-MRS, spectrally selective 3D turbo spin echo for 31P-MRI, and Dixon multi-echo GRE for fat–water imaging on a 3 T clinical MRI scanner. All the subjects were scanned pre-exercise, during plantar flexion exercise, and post-exercise recovery, with two rounds of exercise for 31P -MRS and 31P-MRI, respectively. Unpaired t-tests were used to compare 31P-MRS and 31P-MRI results between the HF and control cohorts. The results show that PCr resynthesis rate was significantly slower in the HF cohort compared to the controls using 31P-MRS (P = 0.0003) and 31P-MRI (P = 0.0014). 31P-MRI showed significant differences between the cohorts in muscle groups (soleus (P = 0.0018), gastrocnemius lateral (P = 0.0007) and gastrocnemius medial (P = 0.0054)). The results from this study suggest that 31P-MRS/31P-MRI may be used to quantify lower leg muscle oxidative metabolism in HF patients, with 31P-MRI giving an additional advantage of allowing further localization of oxidative metabolism deficits. Upon further validation, these techniques may serve as a potentially useful clinical imaging biomarker for staging and monitoring therapies in HF-patients.

Skeletal muscle capillary density is related to anaerobic threshold and claudication in peripheral artery disease.

Peripheral artery disease (PAD) is characterized by impaired blood flow to the lower extremities, causing claudication and exercise intolerance. Exercise intolerance may result from reduced skeletal muscle capillary density and impaired muscle oxygen delivery. This cross-sectional study tested the hypothesis that capillary density is related to claudication times and anaerobic threshold (AT) in patients with PAD. A total of 37 patients with PAD and 29 control subjects performed cardiopulmonary exercise testing on a treadmill for AT and gastrocnemius muscle biopsies. Skeletal muscle capillary density was measured using immunofluorescence staining. PAD had decreased capillary density (278 ± 87 vs 331 ± 86 endothelial cells/mm2, p = 0.05), peak VO2 (15.7 ± 3.9 vs 24.3 ± 5.2 mL/kg/min, p ⩽ 0.001), and VO2 at AT (11.5 ± 2.6 vs 16.1 ± 2.8 mL/kg/min, p ⩽ 0.001) compared to control subjects. In patients with PAD, but not control subjects, capillary density was related to VO2 at AT (r = 0.343; p = 0.038), time to AT (r = 0.381; p = 0.020), and time after AT to test termination (r = 0.610; p ⩽ 0.001). Capillary density was also related to time to claudication (r = 0.332; p = 0.038) and time after claudication to test termination (r = 0.584; p ⩽ 0.001). In conclusion, relationships between capillary density, AT, and claudication symptoms indicate that, in PAD, exercise limitations are likely partially dependent on limited skeletal muscle capillary density and oxidative metabolism.

HDAC11 is a novel regulator of fatty acid oxidative metabolism in skeletal muscle.

Skeletal muscle is the largest tissue in mammalian organisms and is a key determinant of basal metabolic rate and whole-body energy metabolism. Histone deacetylase 11 (HDAC11) is the only member of the class IV subfamily of HDACs, and it is highly expressed in skeletal muscle, but its role in skeletal muscle physiology has never been investigated. Here, we describe for the first time the consequences of HDAC11 genetic deficiency in skeletal muscle, which results in the improvement of muscle function enhancing fatigue resistance and muscle strength. Loss of HDAC11 had no obvious impact on skeletal muscle structure but increased the number of oxidative myofibers by promoting a glycolytic-to-oxidative muscle fiber switch. Unexpectedly, HDAC11 was localized in muscle mitochondria and its deficiency enhanced mitochondrial content. In particular, we showed that HDAC11 depletion increased mitochondrial fatty acid β-oxidation through activating the AMP-activated protein kinase-acetyl-CoA carboxylase pathway and reducing acylcarnitine levels invivo, thus providing a mechanistic explanation for the improved muscle strength and fatigue resistance. Overall, our data reveal a unique role of HDAC11 in the maintenance of muscle fiber-type balance and the mitochondrial lipid oxidation. These findings shed light on the mechanisms governing muscle metabolism and may have implications for chronic muscle metabolic disease management.

Effects Of 10-days Bed-rest On Nitric Oxide Metabolites And Microvascular Function Assessed By Near-infrared Spectroscopy

PURPOSE: Prolonged periods of bed-rest (BR), experimental simulation of microgravity, greatly affect oxidative metabolism by acting at several levels of the O2 pathway. Short duration (10 days) of horizontal BR negatively affects in-vivo functional biomarkers related to skeletal muscle oxidative metabolism without affecting mitochondrial respiration ex-vivo. The impairment of muscle oxidative metabolism can partially derive from reduced O2 delivery, altered peripheral O2 diffusion and a mismatch between O2 delivery and O2 consumption, likely related to an altered nitric oxide signaling. Aim of this study was to evaluate the effects of 10 days of BR on microvascular reactivity indexes determined at skeletal muscle level by near infrared spectroscopy and nitric oxide metabolites. METHODS: Measurements were carried out on 10 recreationally active young males (age 23 ± 5 years [mean±SD]) before (PRE) and after (POST) 10 days of horizontal BR. Pulmonary O2 uptake (V̇O2) and other respiratory, cardiovascular and skeletal muscle variables were determined during an incremental exercise on a cycle ergometer. Microvascular endothelial function was assessed during vascular occlusion test (VOT) by evaluating the slope of re-oxygenation rate (SLOPE 2) and the area under the curve (AUC) over the baseline of 5min reperfusion phase of delta[oxy(Hb+Mb)] signal obtained from vastus lateralis muscle. Plasma nitrite concentration was determined by chemiluminescence. RESULTS: Peak V̇O2 was lower in POST (41.5±6.5 ml.kg-1.min-1) vs. PRE (44.5±7.4, P<0.01). SLOPE 2 was significantly slower in POST (5.3±0.8 %.s-1) compared to PRE (6.4±0.7, P<0.01). AUC was significantly reduced in POST (11025±2145 %.s) compared to PRE (13094±1940, P<0.01). Plasma nitrite concentration diminished from PRE (85.4±35.0 nM) to POST (65.5±45.6, P<0.01). CONCLUSIONS: These preliminary data suggest that after 10 days of horizontal BR whole-body impairment of oxidative metabolism during exercise is associated with reduced level of nitrite and an altered microvascular endothelial function. Further analyses of systemic functional variables as well as biochemical data obtained during the bed-rest campaign, and not yet analysed, will help us to define sites of limitation to muscle oxidative metabolism along the O2 pathway.

Effect of acute nitrite infusion on contractile economy and metabolism in isolated skeletal muscle in situ during hypoxia.

Increased plasma nitrite concentrations may have beneficial effects on skeletal muscle function. The physiological basis explaining these observations has not been clearly defined and it may involve positive effects on muscle contraction force, microvascular O2 delivery and skeletal muscle oxidative metabolism. In the isolated canine gastrocnemius model, we evaluated the effects of acute nitrite infusion on muscle force and skeletal muscle oxidative metabolism. Under hypoxic conditions, but in the presence of normal convective O2 delivery, an elevated plasma nitrite concentration affects neither muscle force, nor muscle contractile economy. In accordance with previous results suggesting limited or no effects of nitrate/nitrite administrations in highly oxidative and highly perfused muscle, our data suggest that neither mitochondrial respiration, nor muscle force generation are affected by acute increased concentrations of NO precursors in hypoxia. Contrasting findings have been reported concerning the effects of augmented nitric oxide (NO) on skeletal muscle force production and oxygen consumption ( ). The present study examined skeletal muscle mitochondrial respiration and contractile economy in an isolated muscle preparation during hypoxia (but normal convective O2 delivery) with nitrite infusion. Isolated canine gastrocnemius muscles in situ (n=8) were studied during 3min of electrically stimulated isometric tetanic contractions corresponding to ∼35% of . During contractions, sodium nitrite (NITRITE) or sodium chloride (SALINE) was infused into the popliteal artery. was calculated from the Fick principle. Experiments were carried out in hypoxia ( =0.12), whereas convective O2 delivery was maintained at normal levels under both conditions by pump-driven blood flow ( ). Muscle biopsies were taken and mitochondrial respiration was evaluated by respirometry. Nitrite infusion significantly increased both nitrite and nitrate concentrations in plasma. No differences in force were observed between conditions. was not significantly different between NITRITE (6.1±1.8mL 100g-1 min-1 ) and SALINE (6.2±1.8mL100g-1 min-1 ), even after being 'normalized' per unit of developed force (muscle contractile economy). No differences between conditions were found for maximal ADP-stimulated mitochondrial respiration (both for complex I and complex II), leak respiration and oxidative phosphorylation coupling. In conclusion, in the absence of changes in convective O2 delivery, muscle force, muscle contractile economy and mitochondrial respiration were not affected by acute infusion of nitrite. The previously reported positive effects of elevated plasma nitrite concentrations are presumably mediated by the increased microvascular O2 availability.

Physiological basis of interval training for performance enhancement.

What is the topic of this review? This review considers the physiological basis of interval training for performance enhancement, with an emphasis on the capacity for aerobic energy provision. What advances does it highlight? It highlights advances regarding the effect of interval training on primary physiological determinants of aerobic energy provision, which are associated with performance. Interval training refers to an intermittent style of exercise, in which bouts of more intense effort are interspersed with recovery periods within a given training session. Physiological responses to interval training depend on numerous factors, including the specific nature of the intervention and the initial training state of the individual. Interval training improves performance in part by enhancing the capacity for aerobic energy provision, even in those who are already trained. Two primary mechanisms in this regard are an increased whole-body maximal oxygen uptake and an enhanced capacity for oxidative metabolism in skeletal muscle owing to an increase in mitochondria. In comparison to moderate-intensity continuous exercise, interval training can elicit superior responses when total work is matched, and similar responses despite a reduced training volume and time commitment.

Receptor for advanced glycation end products modulates oxidative stress and mitochondrial function in the soleus muscle of mice fed a high-fat diet.

Accumulation of advanced glycation end products (AGEs) and activation of the receptor for AGEs (RAGE) are implicated in the progression of pathologies associated with aging, chronic inflammation, diabetes, and cellular stress. RAGE activation is also implicated in cardiovascular complications of type 2 diabetes, such as nephropathy, retinopathy, accelerated vascular diseases, and cardiomyopathy. Studies investigating the effects of AGE/RAGE axis activation on skeletal muscle oxidative stress and metabolism are more limited. We tested whether a high-fat diet (HFD) would alter circulating AGE concentration, skeletal muscle AGE accumulation, and oxidative stress in wild-type and RAGE-deficient mice. The physiological significance of AGE/RAGE axis activation in HFD-fed mice was evaluated in terms of exercise tolerance and mitochondrial respiratory chain complex activity. HFD elicited adiposity, abnormal fat distribution, and oral glucose intolerance. HFD also induced accumulation of Nε-carboxymethyl-l-lysine, increased protein carbonyl levels, and impaired respiratory chain complex activity in soleus muscle. Ablation of RAGE had no effects on weight gain and oral glucose tolerance in HFD-fed mice. Peak aerobic capacity and mitochondrial cytochrome-c oxidase activity were restored in HFD-fed RAGE-/- mice. We concluded that RAGE signaling plays an important role in skeletal muscle homeostasis of mice under metabolic stress. Novelty HFD in mice induces accumulation of AGEs, oxidative stress, and mitochondrial dysfunction in the soleus muscle. RAGE, the multi-ligand receptor for AGEs, modulates oxidative stress and mitochondrial electron transport chain function in the soleus muscle of HFD-fed mice.

Investigating the genetic susceptibility to exertional heat illness

BackgroundWe aimed to identify rare (minor allele frequency ≤1%), potentially pathogenic non-synonymous variants in a well-characterised cohort with a clinical history of exertional heat illness (EHI) or exertional rhabdomyolysis (ER)....

Dietary thymol supplementation promotes skeletal muscle fibre type switch in longissimus dorsi of finishing pigs.

As one of the key points related to meat quality, skeletal muscle fibre type is determined by energy metabolism and genetic factors, but its transformation could be also greatly influenced by many factors. Thymol, the primary effective ingredients of thyme, is well known for its anti-oxidation and anti-inflammatory, while little is known about its effect on skeletal muscle oxidative metabolism and fibre type switch. Therefore, in order to investigate its effects and possibility to be applied in livestock production, 36 150-day-old fattening Pigs were fed with different diet for six-week experiment. As a result, the drip loss ratio of longissimus dorsi (LD) was significantly reduced (p<.05). Oxidative metabolism-related enzyme activity, the mRNA levels and protein expression of COX5B and PGC1α, mRNA level of myosin heavy chain I (MyHC I) and protein level of MyHC IIa were significantly upregulated (p<.05). While compared with control group, the protein expression of MyHC IIb was significantly decreased (p<.05). The result revealed that thymol could promote the oxidative metabolism in the muscle of pigs and improve the meat quality to a certain extent.

Skeletal muscle V̇o2kinetics by the NIRS repeated occlusions method during the recovery from cycle ergometer exercise

Near-infrared spectroscopy (NIRS) has been utilized as a noninvasive method to evaluate skeletal muscle mitochondrial function in humans, by calculating muscle V̇o2 (V̇o2m) recovery (off-) kinetics following short light-intensity plantar flexion exercise. The aim of the present study was to determine V̇o2m off- kinetics following standard cycle ergometer exercise of different intensities. Fifteen young physically active healthy men performed an incremental exercise (INCR) up to exhaustion and two repetitions of constant work-rate (CWR) exercises at 80% of gas exchange threshold (GET; MODERATE) and at 40% of the difference between GET and peak pulmonary V̇o2 (V̇o2p; HEAVY). V̇o2p and vastus lateralis muscle fractional O2 extraction by NIRS (Δ[deoxy(Hb+Mb)]) were recorded continuously. Transient arterial occlusions were carried out at rest and during the recovery for V̇o2m calculation. All subjects tolerated the repeated occlusions protocol without problems. The quality of the monoexponential fitting for V̇o2m off-kinetics analysis was excellent (0.93≤r2≤0.99). According to interclass correlation coefficient, the test-retest reliability was moderate to good. V̇o2m values at the onset of recovery were ~27, ~38, and ~35 times higher (in MODERATE, HEAVY, and INCR, respectively) than at rest. The time constants (τ) of V̇o2m off-kinetics were lower (P < 0.001) following MODERATE (29.1 ± 6.8 s) vs. HEAVY (40.8 ± 10.9) or INCR (42.9 ± 10.9), suggesting an exercise intensity dependency of V̇o2m off-kinetics. Only following MODERATE the V̇o2m off-kinetics were faster than the V̇o2p off-kinetics. V̇o2m off-kinetics, determined noninvasively by the NIRS repeated occlusions technique, can be utilized as a functional evaluation tool of skeletal muscle oxidative metabolism also following conventional cycle ergometer exercise.NEW & NOTEWORTHY This is the first study in which muscle V̇o2 recovery kinetics, determined noninvasively by near-infrared spectroscopy (NIRS) by utilizing the repeated occlusions method, was applied following standard cycle ergometer exercise of different intensities. The results demonstrate that muscle V̇o2 recovery kinetics, determined noninvasively by the NIRS repeated occlusions technique, can be utilized as a functional evaluation tool of skeletal muscle oxidative metabolism also following conventional cycle ergometer exercise, overcoming significant limitations associated with the traditionally proposed protocol.