ABSTRACT Background High‐intensity interval training (HIIT) with or without L‐citrulline (CIT) oral supplementation improves body composition, functional capacities and muscle health in obese older adults, potentially through microRNA‐driven regulation. We aimed to (1) investigate the impact of a 12‐week HIIT on the expression level of microRNAs in vastus lateralis muscle biopsies and serum of obese older adults and (2) assess whether the differential expression level of microRNAs was associated with clinico‐biological adaptations to HIIT and provide potential biomarkers of HIIT response. Methods In this secondary exploratory analysis of a double‐blind randomized trial, 36 women and 32 men (67.2 ± 5.2 years) following 12 weeks HIIT randomized in two groups were supplemented daily with CIT (HIIT‐CIT, n = 37) or with placebo (HIIT‐PLA, n = 31). Phenotypic variables, serum parameters, muscle biopsies and subcutaneous abdominal adipose tissue outcomes were collected pre‐intervention and postintervention. To assess the microRNA profile, the miRNome of muscle biopsy and serum was analysed using next generation sequencing in participants' subsets (n = 13). The microRNAs' differential expression level was analysed pre‐intervention and postintervention by TaqMan‐real‐time qPCR in 68 participants. Results The expression of myo‐microRNAs (miR‐133a, b, ‐1, ‐206) and muscle‐related‐microRNAs (miR‐499, ‐208) was not altered following HIIT with or without CIT. In HIIT‐PLA, HIIT‐CIT and subgroups (based on sex, age, body mass index, dynapenic status), the change in muscle (miR‐504‐5p, ‐744‐5p, ‐151a‐3p, ‐106b‐5p, ‐127‐5p) and circulating (miR‐4433b‐5p, 151a‐3p, ‐744‐5p, 483‐3p, ‐106b‐5p, ‐484) microRNA levels was associated with changes of clinico‐biological parameters. Supplementing HIIT with CIT decreased the muscle miR‐504‐5p level (p = 0.022), correlating with lower body fat, improved functional capacities, muscle power and increased IGF‐1 level (r = −0.6, p < 0.05). MiR‐744‐5p expression increased in dynapenic participants (p = 0.04), associated with lean mass gain (r = 0.50, p < 0.05), while miR‐151a‐3p downregulation in men's muscle (p = 0.01) was associated with better insulin sensitivity (HOMA‐IR, r = 0.57, p = 0.05). In serum, miR‐151a‐3p upregulation in women (p = 0.01) correlated with improved muscle power and lower circulating leptin levels, while miR‐4433b‐5p downregulation (p = 0.001) was linked to reduced fat mass, lean mass gain and enhanced functional capacity. The downregulation of miR‐106b‐5p (p = 0.05) was associated with a higher adiponectin level and a better score of the 4‐m walking test (p = 0.05). Conclusion HIIT did not impact the expression level of myo‐microRNAs and muscle‐related microRNAs but induced changes in muscle‐nonspecific microRNAs in muscle biopsy and serum. Modulations of microRNAs in muscle (miR‐504‐5p, ‐744‐5p) and serum (miR‐151a‐3p, ‐4433b‐5p, ‐106b‐5p) were associated with HIIT's beneficial effects, suggesting their role in the HIIT effects and their potential as candidate biomarkers for response.
Exposure to environmental pollutants may contribute to various health disorders, often manifesting after a prolonged period of latency. The identification of early markers is, therefore, of paramount importance. To achieve this objective, realistic models of environmental exposure were set up. Whereas most studies consider one substance or mixture with one target organ, here, in addition to the liver, two easily accessible sensitive organs, the eyes and teeth, were analyzed as good potential candidates to be original markers of environmental exposures. C57BL/6J mice were exposed to either sodium fluoride or a mixture of 15 endocrine-disrupting substances, or both, in their drinking water from the time of conception until 1 or 10 months after birth. The doses of these substances were chosen to be close to the tolerable daily intake. All mice in test groups presented lower weight gain than controls with the most significant differences observed in females 30 days after birth. Alterations in the eye retina were detected as early as 1 month of age and considerably worsened by 10 months. Dental defects were observed in all test groups at the last time point. At that age, metabolic disruptions were identified through molecular metabolomic and RNAseq analyses, while histological analyses showed no significant defects in liver. This study shows that chronic exposure to widespread toxicants resulted in hepatic metabolic disorders. However, the most evident histological and clinical signs were observed in eyes and teeth. These easily accessible stigmata may be used as early markers of low-dose exposure to environmental toxicants.
The COVID-19 pandemic has significantly reduced physical activity levels in the general population. This study seeks to examine the impact of pandemic-related lockdowns on physical activity among athletes, comparing individuals across different performance levels and countries. A cross-sectional study was employed. Between 5 and 15 April 2020, they were administered the International Physical Activity Questionnaire (IPAQ) and the Short-Form General Health Questionnaire (SF-12) (including SF-12 Physical and Mental Component Summary subscores [PCS and MCS respectively]). Before the lockdown, women had higher energy expenditure (AEE) and physical component scores (PCS) compared to men, while mental component scores MCS were higher for men than for women. During a lockdown, total activity time (TAT) and AEE decreased significantly for all athletes, sitting time increased, and quality of life worsened. TAT, AEE, and PCS became similar between sexes during lockdown, but women had lower MCS at low activity levels, except for high-level female athletes, who showed similar MCS to males. In conclusion, the COVID-19 lockdown negatively impacted athletes’ Total activity time, activity energy expenditure, and quality of life were greater among low-level athletes, particularly females.
Persistent organic pollutants (POPs) are associated with many adverse health effects in humans, including cancers, immune, reproductive, neurological disorders and metabolic diseases. These chemicals are known to accumulate in fatty tissues, from which they can be released in other tissue compartments of living organisms, in particular, upon weight loss. This dynamic distribution of POPs remains, however poorly investigated. In this study, a xenografted POP-contaminated adipose tissue (AT) model was used to assess 1) their concentrations in the ATs, the liver and the brain and 2) their associated effects by transcriptomics, metabolomics and lipidomics approaches. In the ATs, the liver and the brain of mice grafted with POP-contaminated fat pad, most of POPs were detected 3 days and 21 days after the graft with the highest concentrations in the ATs and the lowest concentrations in the brain. Conversely, per- and polyfluoroalkyl substances presented a distinct profile as they persist in the liver but not in the ATs or in the brain. In the AT of POP-exposed mice, the most dysregulated pathways were related to mitochondrial functions, endobiotic (carbohydrate, lipid, amino acid) and xenobiotic metabolism and inflammatory response. In the liver of grafted mice, many pathways related to mitochondrial functions and metabolism were dysregulated. These results support that realistic mixture of POPs that accumulate in AT and liver induces a systemic metabolic dysfunction which may represent the mechanisms by which the POPs can promote metabolic diseases such as obesity, type 2 diabetes and cardiovascular diseases.
BACKGROUND:Achieving a consensus on methods for exercise quantification appears to be a challenging endeavor in sport science. Quantification of exercise enables the description of training in unit doses by coaches and scientists, facilitating subsequent analysis of responses to training. PURPOSE:The present manuscript seeks to provide an overview of the merits and limitations of exercise quantification methods based on the product of exercise intensity × duration and those based on maximum tolerable volume. RESULTS:Intensity × duration methods use parameters to express intensity that are only effective for endurance exercises and could be affected by the possible intermittent format of exercises. In addition, the intensity-duration relationship is not efficiently addressed by these methods, resulting in the overvaluation of prolonged exercises compared with shorter ones. Such limitations do not appear in methods based on maximum volume, which is regarded as an indicator of the maximal dose for a given exercise and can, thus, be used as a reference to quantify the dose of similar exercises. CONCLUSION:Because intensity × duration methods inadequately consider the relationship between the variables that constitute the exercise, their use should be restricted to programs that exhibit minimal variation in exercise intensity and type. Conversely, exercise quantification based on maximal duration takes into account the influence of all exercise variables. This way of quantification can be efficient across a wide range of exercise intensities and types; however, it requires knowledge of exercise maxima, which can be challenging to ascertain in a training context.
AbstractAcute kidneys injuries (AKIs) have been described in marathon and trail running. The currently available data allows assessment of before/after comparisons but does not allow an analysis of what happens during the race. A multidisciplinary assessment protocol was performed during the first trail of Clécy (Normandy France) in November 2021. This allowed an initial assay to be carried out, then at the end of each of the 6 loops of 26 km, and finally after 24 h of recovery. The race extends over 156 km in hilly terrain and 6000 m of elevation gain (D+). The level of impairment according to the RIFLE classification was defined for each runner at each assay. Fifty‐five runners were at the start, and the per protocol analysis involved 36 runners (27 men and 9 women, 26 finishers). Fifteen (41.7%) of the riders presented at least one result corresponding to a “RIFLE risk” level. After 24 h of rest, only one runner still had a “RIFLE Risk”. The distance around the marathon seems to be the moment of greatest risk. For the first time, we find an association between this renal risk and the probability of abandonment. Many runners are vulnerable to kidney damage during long‐duration exercise, which is why it's important to limit risk situations, such as the use of potentially toxic drugs or hydration disorders. The consumption of NSAIDs (nonsteroidal anti‐inflammatory drugs) before or during an ultra‐distance race should therefore be prohibited. Attention should be paid to hydration disorders.
Ultra-trail running races pose appreciable physiological challenges, particularly for glucose metabolism. Previous studies that yielded divergent results only measured glycaemia at isolated times. We aimed to explore the impact of an ultra-endurance race on continuously measured glycaemia and to understand potential physiological mechanisms, as well as the consequences for performance and behavioural alertness. Fifty-five athletes (78
Objective. - As the concept of training load grows in popularity, inconsistencies in definitions and quantification methods used in literature are more and more apparent. To limit such disagreements, principles founding the concept were studied to propose an operational definition of training load that was subsequently used to analyze the accuracy of quantification methods. News. - Training load might be defined as the value describing the dose of effort induced by the combination of the exercise variables. Training load metrics should not be skewed by excess weighting of exercise volume, intensity, or density. Early methods based on the product of intensity, volume, and density do not take into account the non-linear nature of increases in their components, and volume is overexpressed in their training load calculations. Conversely, fatigue achievement may accurately reflect the combined effects of all exercise variables by signaling the maximal psychophysiological stress and in consequence maximal attainable training load. Prospects and projects. - Fatigue-based quantification methods require better understanding and knowledge of exercise maximums. Probably new technologies for athletes monitoring might help to identify and record such maximums. Conclusion. - The present paper supported that for comparisons of exercises effects and to accumulate exercises of a program in total training load, the dose should be expressed relative to exercises maximums what drives to fatigue-based quantification methods. (c) 2023 Published by Elsevier Masson SAS.
Physical activity can be effective in preventing some of the adverse effects of aging on health. High-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) are beneficial interventions for the quality of life of obese older individuals. The understanding of all possible metabolic mechanisms underlying these beneficial changes has not yet been established. The aim of this study was to analyze changes in the serum metabolome after 12 weeks of HIIT and MICT in obese older adults. Thirty-eight participants performed either HIIT (n = 26) or MICT (n = 12) three times per week for 12 weeks. Serum metabolites as well as clinical and biological parameters were assessed before and after the 12-week intervention. Among the 364 metabolites and ratio of metabolites identified, 51 metabolites changed significantly following the 12-week intervention. Out of them, 21 significantly changed following HIIT intervention and 18 significantly changed following MICT. Associations with clinical and biological adaptations revealed that changes in acyl-alkyl-phosphatidylcholine (PCae) (22:1) correlated positively with changes in handgrip strength in the HIIT group (r = 0.52, p < 0.01). A negative correlation was also observed between 2-oxoglutaric acid and HOMA-IR (r = −0.44, p < 0.01) when considering both groups together (HIIT and MICT). This metabolite also correlated positively with quantitative insulin-sensitivity check index (QUICKI) in both groups together (r = 0.46, p < 0.01) and the HIIT group (r = 0.51, p < 0.01). Additionally, in the MICT group, fumaric acid was positively correlated with triglyceride levels (r = 0.73, p < 0.01) and acetylcarnitine correlated positively with low-density lipoprotein (LDL) cholesterol (r = 0.81, p < 0.01). These four metabolites might represent potential metabolites of interest concerning muscle strength, glycemic parameters, as well as lipid profile parameters, and hence, for a potential healthy aging. Future studies are needed to confirm the association between these metabolites and a healthy aging.
BACKGROUND Only few studies analyzed real training programs of sprinters while that should be a valuable step in the understanding of sprint training. The present study aimed at characterizing track cycling sprinter training by training load and intensity distribution. METHODS Twenty-nine weeks of prechampionship training data were retrospectively analyzed for 6 world-class athletes. Training load was measured by the ratio of volume completed to maximal volume and categorized by five intensity zones (endurance: zones1-2; sprinting: zones3-5) and exercise type (on-bike or resistance). Intra-week (training monotony) and inter-week (acute-chronic workload ratio) variation was also studied. RESULTS On-bike training represented 77.4±15.3% of total training load; resistance training, 22.6±15.2% (note high standard deviation). Total weekly training load significantly varied (P=0.0002) with high acute-chronic workload ratio (12.0±3.2 weeks >1.5 or <0.8), but low intra-week variations (training monotony, 1.81±0.20). Zone4 and zone5 made up 74.4±16.9% of total training load; zone1, 15.8±11%. Training load was seldom in zone2 (6.4±5.3%) or zone3 (3.3±4.2%). From the first to the second half of the period, zone3-4 training load decreased (39.3±3.3 to 27.4±1.7%; P=0.01), while zone5 increased (34.9±2.4 to 50±3.7%; P=0.002). CONCLUSIONS In this reduced group of elite athletes, training appeared to mainly consist of on-bike exercises within the highest intensity zones. As demonstrated by monotony and acute-chronic workload ratio overloading and unloading are based on high variations over weeks, not days. Essentially, this study describes a polarized intensity distribution on the highest intensities which increased with world championships approach.
Le vieillissement est associé à un déclin progressif de la masse et de la force musculaires squelettiques ainsi qu'à une augmentation de l'adiposité. Ces changements peuvent avoir un impact néfaste sur la qualité de vie des personnes âgées. Nous avons récemment suggéré que le HIIT combiné à une supplémentation en citrulline (CIT) était une intervention efficace pour améliorer l'état de santé des personnes âgées obèses (Marcangelli PMID : 35257499). En effet, l'ajout de CIT au HIIT entraîne une augmentation plus importante de la force musculaire et une diminution significative de la masse adipeuse. Notre objectif est maintenant de déterminer s'il existe des différences entre les femmes et les hommes dans ces adaptations. Des participants âgés obèses ont suivi, durant 12 semaines, un programme HIIT sur elliptique avec ou sans CIT [HIIT-CIT : 20 hommes/25 femmes, 67,2 ± 5,0 ans ; HIIT-placebo (PLA) : 18 hommes/18 femmes, 68,1 ± 4,1 ans]. Avant (T0) et après (T12) l'intervention, (1) la force de préhension et des quadriceps, la puissance musculaire des membres inférieurs, la composition corporelle (absorptiométrie biphotonique à rayons X) et les capacités fonctionnelles ont été évalués, et (2) des prélèvements sanguins ont été réalisés. Le profil classique en cholestérol (cholestérol total, LDL, « Low Density lipoprotein » et HDL, « High Density lipoprotein ») a été déterminé au McGill University Health Center. Les profils métabolomique et lipoprotéique ont été déterminés par résonance magnétique nucléaire sur le plateau Metabo-Paris-Santé. En utilisant une approche générale linéaire mixte (Anova à 3 facteurs et mesures répétées), seulement chez les femmes, la masse adipeuse totale diminue (T0 : 39,8 ± 6,4 vs T12 : 38,6 ± 6,2, p < 0,01, en %) ainsi que la masse adipeuse des jambes (T0 : 11,7 ± 3,1 vs T12 : 11,3 ± 3, p < 0,05, en kg). En revanche, seulement chez les hommes, la masse adipeuse gynoïde (T0 : 32,9 ± 5,6 vs T12 : 30,9 ± 5,7, p < 0,05, en %) et des membres supérieurs diminuent (T0 : 29,8 ± 5,3 vs 28 ± 5,6, p < 0,01, en %) ainsi que la masse maigre gynoïde (T0 : 8,2 ± 0,9 vs T12 : 8,5 ± 1, en kg). Concernant le cholestérol total et le cholestérol LDL, ils diminuent seulement chez les femmes (respectivement T0 : 5,7 ± 1 vs T12 : 5,4 ± 0,8, p < 0,05, et T0 : 4,1 ± 0,9 vs T12 : 3,8 ± 0,7, p < 0,05, en mmol.L-1). Ces résultats ont été confirmés et précisés par une analyse multivariée à partir d'analyses métabolomiques des échantillons sanguins. En effet, les profils métabolomiques et lipoprotéiques sont différents chez les femmes et les hommes. Nous observons de manière générale une augmentation des VLDL (« Very LDL ») et une diminution des LDL. Spécifiquement chez l'homme, on observe aussi une augmentation du HDL. L'augmentation des VLDL a un poids beaucoup plus élevé dans le modèle pour les femmes. L'ajout de CIT à un programme de HIIT entraîne globalement une diminution significative de la masse adipeuse et une amélioration du profil lipoprotéique. Ceci suggérerait une amélioration de la santé des sujets âgés obèses ayant suivi ce programme. Néanmoins, les adaptations induites semblent différentes entre les femmes et les hommes. Leur profil lipoprotéique semble s'adapter différemment. D'autres études seront nécessaires pour confirmer ces résultats et pour comprendre les mécanismes de ces adaptations.
La popularité croissante du concept de charge d'entraînement (CE) fait apparaître d'évidentes incohérences dans les définitions et les méthodes de quantification utilisées dans la littérature. Pour les limiter, les principes fondateurs du concept ont été utilisés pour proposer une définition opérationnelle de la CE permettant par la suite d'analyser la pertinence des méthodes de quantification actuelles. La CE peut être définie comme la valeur décrivant la dose d'effort induite par la combinaison des variables d'exercice. Les mesures de CE ne doivent pas être faussées par une pondération excessive du volume, de l'intensité ou de la densité de l'exercice. Les premières méthodes de quantification fondées sur le produit de l'intensité, du volume et de la densité ne tiennent pas compte de la nature non linéaire de leur relation et surévaluent l'influence du volume dans leurs calculs. Inversement, l'atteinte de la fatigue peut refléter avec précision les effets combinés de toutes les variables d'exercice en signalant le stress psychophysiologique maximal et, par conséquent, la CE maximale réalisable. Les méthodes de quantification fondées sur la fatigue exigent une meilleure compréhension et connaissance des maximums d'exercice. Les nouvelles technologies de suivi des athlètes pourraient aider à déterminer et enregistrer ces maximums. Cet article suggère que, pour comparer les effets des exercices et pour accumuler des exercices dans une CE totale, la dose devrait être exprimée par rapport aux maximums des exercices résultant en CE fondées sur la fatigue. As the concept of training load grows in popularity, inconsistencies in definitions and quantification methods used in literature are more and more apparent. To limit such disagreements, principles founding the concept were studied to propose an operational definition of training load that was subsequently used to analyze the accuracy of quantification methods. Training load might be defined as the value describing the dose of effort induced by the combination of the exercise variables. Training load metrics should not be skewed by excess weighting of exercise volume, intensity, or density. Early methods based on the product of intensity, volume, and density do not take into account the non-linear nature of increases in their components, and volume is overexpressed in their training load calculations. Conversely, fatigue achievement may accurately reflect the combined effects of all exercise variables by signaling the maximal psychophysiological stress and in consequence maximal attainable training load. Fatigue-based quantification methods require better understanding and knowledge of exercise maximums. Probably new technologies for athletes monitoring might help to identify and record such maximums. The present paper supported that for comparisons of exercises effects and to accumulate exercises of a program in total training load, the dose should be expressed relative to exercises maximums what drives to fatigue-based quantification methods.
Nowadays, exposure to endocrine-disrupting chemicals (EDCs), including persistent organic pollutants (POPs), is one of the most critical threats to public health. EDCs are chemicals that mimic, block, or interfere with hormones in the body's endocrine system and have been associated with a wide range of health issues. This innovative, untargeted metabolomics study investigates chronic low-dose internal exposure to a cocktail of POPs on multiple tissues that are known to accumulate these lipophilic compounds. Interestingly, the metabolic response differs among selected tissues/organs in mice. In the liver, we observed a dynamic effect according to the exposure time and the doses of POPs. In the brain tissue, the situation is the opposite, leading to the conclusion that the presence of POPs immediately gives a saturated effect that is independent of the dose and the duration of exposure studied. By contrast, for the adipose tissues, nearly no effect is observed. This metabolic profiling leads to a holistic and dynamic overview of the main metabolic pathways impacted in lipophilic tissues by a cocktail of POPs.
Physical activity and nutrition play important roles in preventing adverse health outcomes that accompany aging. It has been shown that high-intensity interval training (HIIT) combined with citrulline (CIT) supplementation can improve physical and functional capacities. The aim of this study was to evaluate serum metabolites following a 12-week HIIT combined or not with CIT in obese older adults, and to correlate the metabolic changes with clinico-biological parameters changes. Eighty-six obese older adults completed a 12-week HIIT program combined with a 10 g daily supplementation of either CIT or placebo (PLA) during a double-blinded randomized interventional trial. Only participants with blood samples at T0 (before the intervention) and/or T12 (after the intervention) were included in our sub-analysis (HIIT-PLA-T0: n = 44 and HIIT-PLA-T12: n = 28; HIIT-CIT-T0: n = 39 and HIIT-CIT-T12: n = 42). Serum samples were analyzed by different liquid or gas phase chromatography methods coupled to mass spectrometry. Among the identified metabolites, 44 changed significantly following the 12-week intervention (Time effect), and 10 of them were more affected when HIIT was combined with CIT (Time × Supp effect). Arginine increased significantly due to the 12-week intervention. Correlation analyses demonstrated that decreased triglyceride (TG) (16:1/18:1/16:0) and aspartic acid significantly correlated with a reduction of adiposity-related parameters (fat mass, leg lean mass, leptin, total triglycerides and low-density lipoprotein). Arginine, TG (16:1/18:1/16:0) and aspartic acid might constitute biomarkers of cardiometabolic health and adiposity. Further studies are needed to confirm these associations and understand the underlying mechanisms.Highlights A 12-week intervention involving high-intensity interval training (HIIT) with or without citrulline (CIT) supplementation induced adaptations in the serum metabolome of obese older adults through significant changes in 44 metabolites.Changes in 23 metabolites were observed when a CIT supplementation was administered along with a 12-week HIIT intervention.TG (16:1/18:1/16:0) correlated with several adiposity parameters including leptin, triglycerides, legs lean mass.Aspartic acid correlated with several adiposity parameters including leptin, LDL cholesterol as well as android, arms and trunk fat mass.
Abstract Background Iron excess has been proposed as an essential factor in skeletal muscle wasting. Studies have reported correlations between muscle iron accumulation and atrophy, either through ageing or by using experimental models of secondary iron overload. However, iron treatments performed in most of these studies induced an extra‐pathophysiological iron overload, more representative of intoxication or poisoning. The main objective of this study was to determine the impact of iron excess closer to pathophysiological conditions on structural and metabolic adaptations (i) in differentiated myotubes and (ii) in skeletal muscle exhibiting oxidative (i.e. the soleus) or glycolytic (i.e. the gastrocnemius) metabolic phenotypes. Methods The impact of iron excess was assessed in both in vitro and in vivo models. Murine differentiated myotubes were exposed to ferric ammonium citrate (FAC) (i.e. 10 and 50 μM) for the in vitro component. The in vivo model was achieved by a single iron dextran subcutaneous injection (1 g/kg) in mice. Four months after the injection, soleus and gastrocnemius muscles were harvested for analysis. Results In vitro, iron exposure caused dose‐dependent increases of iron storage protein ferritin (P < 0.01) and dose‐dependent decreases of mRNA TfR1 levels (P < 0.001), which support cellular adaptations to iron excess. Extra‐physiological iron treatment (50 μM FAC) promoted myotube atrophy (P = 0.018), whereas myotube size remained unchanged under pathophysiological treatment (10 μM FAC). FAC treatments, whatever the doses tested, did not affect the expression of proteolytic markers (i.e. NF‐κB, MurF1, and ubiquitinated proteins). In vivo, basal iron content and mRNA TfR1 levels were significantly higher in the soleus compared with the gastrocnemius (+130% and +127%; P < 0.001, respectively), supporting higher iron needs in oxidative skeletal muscle. Iron supplementation induced muscle iron accumulation in the soleus and gastrocnemius muscles (+79%, P < 0.001 and +34%, P = 0.002, respectively), but ferritin protein expression only increased in the gastrocnemius (+36%, P = 0.06). Despite iron accumulation, muscle weight, fibre diameter, and myosin heavy chain distribution remained unchanged in either skeletal muscle. Conclusions Together, these data support that under pathophysiological conditions, skeletal muscle can protect itself from the related deleterious effects of excess iron.