NMR metabolomics study of chronic low-dose exposure to a cocktail of persistent organic pollutants.

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.

Alteration of performance in a mouse model of Emery-Dreifuss muscular dystrophy caused by A-type lamins gene mutation.

Autosomal Emery-Dreifuss muscular dystrophy (EDMD) is caused by mutations in the lamin A/C gene (LMNA) encoding A-type nuclear lamins, intermediate filament proteins of the nuclear envelope. Classically, the disease manifests as scapulo-humero-peroneal muscle wasting and weakness, early joint contractures and dilated cardiomyopathy with conduction blocks; however, variable skeletal muscle involvement can be present. Previously, we and other demonstrated altered activity of signaling pathways in hearts and striated muscles of LmnaH222P/H222P mice, a model of autosomal EDMD. We showed that blocking their activation improved cardiac function. However, the evaluation of the benefit of these treatments on the whole organism is suffering from a better knowledge of the performance in mouse models. We show in the present study that LmnaH222P/H222P mice display a significant loss of lean mass, consistent with the dystrophic process. This is associated with altered VO2 peak and respiratory exchange ratio. These results showed for the first time that LmnaH222P/H222P mice have decreased performance and provided a new useful means for future therapeutic interventions on this model of EDMD.

Relationship between protein intake and bone architecture or bone mineral density among dynapenic-obese older adults.

OBJECTIVE: The current study aimed to assess the relationship between protein intake and bone parameters among dynapenic-obese older adults. DESIGN: The current study is a secondary analysis with an a posteriori and exploratory design. SETTING: Subjects were recruited from the community via social communication (flyers and meetings in community centres) in the Great Montreal area. PARTICIPANTS: Twenty-six subjects were divided a posteriori into two groups according to their usual protein intake: PROT-: < 1 g/kg per d (n 13; women: 53·8 %; 66·5 (sd 3·3) years) and PROT+: > 1·2 g/kg per d (n 13; women: 61·5 %; 67·2 (sd 2·7) years). RESULTS: Both groups were comparable for age (PROT-: 66·5 (sd 3·3) v. PROT+: 67·2 (sd 2·7) years, P = 0·61) and gender (women: PROT-: n 7; 53·8 % v. PROT+: n 8; 61·5 %, P = 0·69). The PROT- group had a higher marrow area (P = 0·049), a greater bone compressive strength (P = 0·048) and a larger total bone area (P = 0·045) than the PROT+ group. However, no significant difference between the two groups was observed regarding body composition (fat and lean masses) or muscle composition. CONCLUSIONS: A lower protein intake seems to be associated with bone sizes, which influence bone strength, but do not influence bone density among dynapenic-obese older people.

Endurance training reduces exercise-induced acidosis and improves muscle function in a mouse model of sickle cell disease.

Sickle cell disease (SCD) mice (Townes model of SCD) presented exacerbated exercise-induced acidosis and fatigability as compared to control animals. We hypothesize that endurance training could represent a valuable approach to reverse these muscle defects. Endurance-trained HbAA (HbAA-END, n=10), HbAS (HbAS-END, n=11) and HbSS (HbSS-END, n=8) mice were compared to their sedentary counterparts (10 HbAA-SED, 10 HbAS-SED and 9 HbSS-SED mice) during two rest - exercise - recovery protocols during which muscle energetics and function were measured. In vitro analyses of some proteins involved in muscle energetics, pH regulation and oxidative stress were also performed. Exercise-induced acidosis was lower in HbSS-END mice as compared to their sedentary counterparts during both moderate (p<0.001) and intense (p<0.1) protocols. The total force production measured during both protocols was higher in trained mice compared to sedentary animals. In vitro analyses revealed that enolase/citrate synthase ratio was reduced in HbSS-END (p<0.001) and HbAS-END (p<0.01) mice compared to their sedentary counterparts. In addition, malondialdehyde concentration was reduced in trained mice (p<0.05). In conclusion, endurance training would reverse the more pronounced exercise-induced acidosis, reduce oxidative stress and ameliorate some of the muscle function parameters in SCD mice.

Gonad-related factors promote muscle performance gain during postnatal development in male and female mice.

To better define the role of male and female gonad-related factors (MGRF, presumably testosterone, and FGRF, presumably estradiol, respectively) on mouse hindlimb skeletal muscle contractile performance/function gain during postnatal development, we analyzed the effect of castration initiated before puberty in male and female mice. We found that muscle absolute and specific (normalized to muscle weight) maximal forces were decreased in 6-mo-old male and female castrated mice compared with age- and sex-matched intact mice, without alteration in neuromuscular transmission. Moreover, castration decreased absolute and specific maximal powers, another important aspect of muscle performance, in 6-mo-old males, but not in females. Absolute maximal force was similarly reduced by castration in 3-mo-old muscle fiber androgen receptor (AR)-deficient and wild-type male mice, indicating that the effect of MGRF was muscle fiber AR independent. Castration reduced the muscle weight gain in 3-mo mice of both sexes and in 6-mo females but not in males. We also found that bone morphogenetic protein signaling through Smad1/5/9 was not altered by castration in atrophic muscle of 3-mo-old mice of both sexes. Moreover, castration decreased the sexual dimorphism regarding muscle performance. Together, these results demonstrated that in the long term, MGRF and FGRF promote muscle performance gain in mice during postnatal development, independently of muscle growth in males, largely via improving muscle contractile quality (force and power normalized), and that MGFR and FGRF also contribute to sexual dimorphism. However, the mechanisms underlying MGFR and FGRF actions remain to be determined.

Synergistic effects of citrulline supplementation and exercise on performance in male rats: evidence for implication of protein and energy metabolisms.

Background: Exercise and citrulline (CIT) are both regulators of muscle protein metabolism. However, the combination of both has been under-studied yet may have synergistic effects on muscle metabolism and performance. Methods: Three-month-old healthy male rats were randomly assigned to be fed ad libitum for 4 weeks with either a citrulline-enriched diet (1 g·kg-1·day-1) (CIT) or an isonitrogenous standard diet (by addition of nonessential amino acid) (Ctrl) and trained (running on treadmill 5 days·week-1) (ex) or not. Maximal endurance activity and body composition were assessed, and muscle protein metabolism (protein synthesis, proteomic approach) and energy metabolism [energy expenditure, mitochondrial metabolism] were explored. Results: Body composition was affected by exercise but not by CIT supplementation. Endurance training was associated with a higher maximal endurance capacity than sedentary groups (P<0.001), and running time was 14% higher in the CITex group than the Ctrlex group (139±4 min versus 122±6 min, P<0.05). Both endurance training and CIT supplementation alone increased muscle protein synthesis (by +27% and +33%, respectively, versus Ctrl, P<0.05) with an additive effect (+48% versus Ctrl, P<0.05). Mitochondrial metabolism was modulated by exercise but not directly by CIT supplementation. However, the proteomic approach demonstrated that CIT supplementation was able to affect energy metabolism, probably due to activation of pathways generating acetyl-CoA. Conclusion: CIT supplementation and endurance training in healthy male rats modulates both muscle protein and energy metabolisms, with synergic effects on an array of parameters, including performance and protein synthesis.

Citrulline Supplementation Induces Changes in Body Composition and Limits Age-Related Metabolic Changes in Healthy Male Rats.

BACKGROUND: Aging is associated with profound metabolic disturbances, and citrulline may be of use to limit them. OBJECTIVE: The aim of this work was to evaluate the long-term effect of citrulline supplementation on metabolism in healthy aged rats. METHODS: Twenty-month-old male rats were randomly assigned to be fed (ad libitum) for 12 wk with either a citrulline-enriched diet (1 g ⋅ kg(-1) ⋅ d(-1)) or a standard diet [rendered isonitrogenous by addition of nonessential amino acids (NEAAs)]. Motor activity and muscle strength were measured, body composition was assessed, and muscle metabolism (protein structure, mitochondrial exploration, and transductional factors) and lipid metabolism (lipoprotein composition and sensitivity to oxidative stress) were explored. RESULTS: Compared with the NEAA-treated group, citrulline supplementation was associated with lower mortality (0% vs. 20%; P = 0.05), 9% higher lean body mass (P < 0.05), and 13% lower fat mass (P < 0.05). Compared with the NEAA-treated group, citrulline-treated rats had greater muscle mass (+14-48% depending on type of muscle; P < 0.05 for tibialis, gastrocnemius, and plantaris). Susceptibility to oxidation of lipoproteins, as measured by the maximal concentration of 7-ketocholesterol after copper-induced VLDL and LDL oxidation, was lower in citrulline-treated rats than in NEAA-treated rats (187 ± 8 µmol/L vs. 243 ± 7 µmol/L; P = 0.0005). CONCLUSIONS: Citrulline treatment in male aged rats favorably modulates body composition and protects against lipid oxidation and, thus, emerges as an interesting candidate to help prevent the aging process.

Prediction of one-repetition maximum from submaximal ratings of perceived exertion in older adults pre- and post-training.

BACKGROUND: Individual's one-repetition maximum (1-RM) is required to calculate and prescribe intensity for resistance training, while testing protocols enhance the risk of injuries and are time-consuming. AIMS: The aim of the present study was to assess the accuracy of 1-RM prediction from ratings of perceived exertion (RPE) of resistance exercises performed at submaximal sets (intensity and volume) in older adult males before and after a 12-week rehabilitation program. METHODS: 18 untrained subjects (70.4 ± 4.5 years) first completed a 1-RM direct assessment with a horizontal leg press pre- and post-training. Thereafter, participants performed, in a random order, 2-repetition sets with loads unknown to them (corresponding to 20, 45 and 70 % of 1-RM). The RPE was recorded immediately after the sets. That RPE associated to its corresponding load was subjected to a linear regression analysis to extrapolate the maximal RPE score and its corresponding 1-RM. RESULTS: RPE and relative intensities of sets appeared related pre- [r (2) = 0.59, standard error of estimate (SEE) = 13.3 %] and post-training (r (2) = 0.83, SEE = 8.1 %). Differences between measured and predicted 1-RM were reduced from the beginning to the end of training but standard deviations remained high (17.4 ± 11.8 vs. 4.2 ± 11.1 kg). Pre-training, 1-RM expressed relatively to body weight was negatively related with the errors of 1-RM predictions (r (2) = 0.39, p = 0.03). CONCLUSIONS: In older subjects, RPE may be used to predict 1-RM; however, the predicted value deviates considerably from the measured one, necessitating cautious application. Importantly, this method allows to capture training-induced change in 1-RM, thus making possible assessing training's effectiveness and allowing its modification if necessary.

Increased risk of acute kidney injury in the first part of an ultra-trail-Implications for abandonment.

Acute 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.

Glycaemic Effects of a 156-km Ultra-trail Race in Athletes: An Observational Field Study.

BACKGROUND: Ultra-trail running races pose appreciable physiological challenges, particularly for glucose metabolism. Previous studies that yielded divergent results only measured glycaemia at isolated times. OBJECTIVES: 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. METHODS: Fifty-five athletes (78% men, 43.7 ± 9.6 years) ran a 156-km ultra-trail race (six 26-km laps, total elevation 6000 m). Participants wore a masked continuous glucose monitoring sensor from the day before the race until 10 days post-race. Blood was taken at rest, during refuelling stops after each lap, and after 24-h recovery. Running intensity (% heart rate reserve), performance (lap times), psychological stress, and behavioural alertness were explored. Linear mixed models and logistic regressions were carried out. RESULTS: No higher risk of hypo- or hyperglycaemia was observed during the exercise phases of the race (i.e. excluding stops for scientific measurements and refuelling) compared with resting values. Laps comprising a greater proportion of time spent at maximal aerobic intensity were nevertheless associated with more time > 180 mg/dL (P = 0.021). A major risk of hyperglycaemia appeared during the 48-h post-race period compared with pre-race (P < 0.05), with 31.9% of the participants spending time with values > 180 mg/dL during recovery versus 5.5% during resting. Changes in circulating insulin, cortisol, and free fatty acids followed profiles comparable with those usually observed during traditional aerobic exercise. However, creatine phosphokinase, and to a lesser extent lactate dehydrogenase, increased exponentially during the race (P < 0.001) and remained high at 24-h post-race (P < 0.001; respectively 43.6 and 1.8 times higher vs. resting). Glycaemic metrics did not influence physical performance or behavioural alertness. CONCLUSION: Ultra-endurance athletes were exposed to hyperglycaemia during the 48-h post-race period, possibly linked to muscle damage and inflammation. Strategies to mitigate muscle damage or subsequent inflammation before or after ultra-trail races could limit recovery hyperglycaemia and hence its related adverse health consequences. TRIAL REGISTRATION NUMBER: NCT05538442 2022-09-21 retrospectively registered.

Citrulline enhances myofibrillar constituents expression of skeletal muscle and induces a switch in muscle energy metabolism in malnourished aged rats.

Citrulline (Cit) actions on muscle metabolism remain unclear. Those latter were investigated using a proteomic approach on Tibialis muscles from male Sprague-Dawley rats. At 23 months of age, rats were either fed ad libitum (AL group) or subjected to dietary restriction for 12 weeks. At the end of the restriction period, one group of rats was euthanized (R group) and two groups were refed for one week with a standard diet supplemented with nonessential amino acids group or Cit (CIT group). Results of the proteomic approach were validated using targeted Western blot analysis and assessment of gene expression of the related genes. Maximal activities of the key enzymes involved in mitochondrial functioning were also determined. Cit supplementation results in a significant increase in the protein expression of the main myofibrillar constituents and of a few enzymes involved in glycogenolysis and glycolysis (CIT vs. AL and R, p < 0.05). Conversely, the expression of oxidative enzymes from Krebs cycle and mitochondrial respiratory chain was significantly decreased (CIT vs. AL, p < 0.05). However, maximal activities of key enzymes of mitochondrial metabolism were not significantly affected, except for complex 1 which presented an increased activity (CIT vs. AL and R, p < 0.05). In conclusion, Cit supplementation increases expression of the main myofibrillar proteins and seems to induce a switch in muscle energy metabolism, from aerobia toward anaerobia.

Training load and intensity distribution for sprinting among world-class track cyclists.

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.

Serum Metabolome Adaptations Following 12 Weeks of High-Intensity Interval Training or Moderate-Intensity Continuous Training in Obese Older Adults.

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.

Serum metabolomic adaptations following a 12-week high-intensity interval training combined to citrulline supplementation in obese older adults.

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.

Effect of Aerobic Exercise at Different Intensities on Intraocular Pressure in Young Males.

PRCIS: High intensity aerobic exercise significantly reduced intraocular pressure in healthy young male adults. OBJECTIVE: This study sought to determine how aerobic exercise at various intensities affects intraocular pressure (IOP) in young adults. DESIGN: A repeated measures design was adopted. PARTICIPANTS: A group of 20 volunteers (mean age: 21.24±1.73 y) took part in this study. METHODS: IOP was measured with a tonometer (iCare TA01i, Icare Finland, Finland). Subjects completed 4 cycle ergometer sessions. During the first session, power was increased by 60 W every 3 minutes until exhaustion, corresponding to peak power. For the 3 following tests, each lasting 25 minutes, subjects exercised at intensities of 50%, 70%, and 85% of peak power, respectively, and measurements were taken every 5 minutes. MAIN OUTCOME MEASURES: IOP, as determined using a tonometer, was the primary measure. RESULTS: There was a significant reduction ( P <0.05) in IOP of both eyes during the 25 minutes high-intensity (85%) exercise test. There were also significant interactions between exercise durations and intensities. During high-intensity exercise, IOP, blood pressure, blood lactate, and the rating of perceived exertion were significantly related ( P <0.01). CONCLUSIONS: These data show a significant reduction in IOP at high-intensity aerobic exercise, which may have implications for the management of ocular health.

COVID-19 and aerobic exercise: possible role of angiotensin converting enzyme 2.

The emergence and circulation of a novel coronavirus (2019-nCoV)-Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-set off a global health crisis. SARS-CoV-2 spreads faster than its two ancestors, SARS-CoV and MERS-CoV. Several modes of transmission have been identified: via respiratory droplets, contact with infected people or contaminated surfaces, and potentially, bioaerosols. Various countries have taken preventive measures that may include partial or total lockdowns lasting weeks. The physical inactivity associated with lockdowns may promote cardiometabolic or other diseases, while physical activity may play a critical role in preventing them. Here we develop the hypothesis of the involvement of aerosols in the contamination process, the role of angiotensin converting enzyme 2 (ACE2), the potential benefits and harm of physical activity during lockdowns, and we suggest directions for future research.

Clinical and Biological Adaptations in Obese Older Adults Following 12-Weeks of High-Intensity Interval Training or Moderate-Intensity Continuous Training.

Sarcopenia and obesity are considered a double health burden. Therefore, the implementation of effective strategies is needed to improve the quality of life of older obese individuals. The aim of this study was to compare the impact of high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) on functional capacities, muscle function, body composition and blood biomarkers in obese older adults. Adipose tissue gene expression and markers of muscle mitochondrial content and quality control involved in exercise adaptations were also investigated. Sixty-eight participants performed either HIIT (n = 34) on an elliptical trainer or MICT (n = 34) on a treadmill, three times per week for 12 weeks. HIIT produced significantly higher benefits on some physical parameters (six-minute walking test (HIIT: +12.4% vs. MICT: +5.2%); step test (HIIT: +17.02% vs. MICT: +5.9%); ten-repetition chair test (HIIT: -17.04% vs. MICT: -4.7%)). Although both HIIT and MICT led to an improvement in lower limb power (HIIT: +25.2% vs. MICT: +20.4%), only MICT led to higher improvement in lower limb muscle strength (HIIT: +4.3% vs. MICT: +23.2%). HIIT was more beneficial for increasing total lean body mass (HIIT: +1.58% vs. MICT: -0.81%), while MICT was more effective for decreasing relative gynoid fat mass (HIIT: -1.09% vs. MICT: -4.20%). Regarding adipose tissue gene expression, a significant change was observed for cell death-inducing DFFA (DNA fragmentation factor-alpha)-like effector A (CIDEA) in the HIIT group (A.U; HIIT at T0: 32.10 ± 39.37 vs. HIIT at T12: 48.2 ± 59.2). Mitochondrial transcription factor A (TFAM) content, a marker of mitochondrial biogenesis, increased significantly following HIIT (+36.2%) and MICT (+57.2%). A significant increase was observed in the HIIT group for Translocase of Outer Membrane 20 (TOM20; +54.1%; marker of mitochondrial content), Mitofusin-2 (MFN2; +71.6%; marker of mitochondrial fusion) and Parkin RBR E3 Ubiquitin Protein Ligase (PARKIN; +42.3%; marker of mitophagy). Overall, our results indicate that even though MICT (walking on treadmill) and HIIT (on an elliptical) are effective intervention strategies in obese older adults, HIIT appears to have slightly more beneficial effects. More specifically, HIIT led to higher improvements than MICT on functional capacities, lean mass and skeletal muscle markers of mitochondrial content, fusion, and mitophagy. Thus, MICT but also HIIT (time-efficient training) could be recommended as exercise modalities for obese older adults to maintain or improve mobility, health and quality of life.

Oxidative and glycolytic skeletal muscles deploy protective mechanisms to avoid atrophy under pathophysiological iron overload.

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.

Impact of high-intensity interval training with or without l-citrulline on physical performance, skeletal muscle, and adipose tissue in obese older adults.

BACKGROUND: Aging is associated with a progressive decline in skeletal muscle mass and strength as well as an increase in adiposity. These changes may have devastating impact on the quality of life of older adults. Mitochondrial dysfunctions have been implicated in aging-related and obesity-related deterioration of muscle function. Impairments in mitochondrial quality control processes (biogenesis, fusion, fission, and mitophagy) may underlie this accumulation of mitochondrial dysfunction. High-intensity interval training (HIIT) was shown to improve muscle and mitochondrial function in healthy young and old adults and to improve body composition in obese older adults. Recent studies also positioned citrulline (CIT) supplementation as a promising intervention to counter obesity-related and aging-related muscle dysfunction. In the present study, our objectives were to assess whether HIIT, alone or with CIT, improves muscle function, functional capacities, adipose tissue gene expression, and mitochondrial quality control processes in obese older adults. METHODS: Eighty-one-old and obese participants underwent a 12 week HIIT with or without CIT on an elliptical trainer [HIIT-CIT: 20 men/25 women, 67.2 ± 5.0 years; HIIT-placebo (PLA): 18 men/18 women, 68.1 ± 4.1 years]. Handgrip and quadriceps strength, lower limb muscle power, body composition, waist circumference, and functional capacities were assessed pre and post intervention. Vastus lateralis muscle biopsies were performed in a subset of participants to quantify markers of mitochondrial content (TOM20 and OXPHOS subunits), biogenesis (TFAM), fusion (MFN1&2, OPA1), fission (DRP1), and mitophagy (Parkin). Subcutaneous abdominal adipose tissue biopsies were also performed to assess the expression of genes involved in lipid metabolism. RESULTS: HIIT-PLA and HIIT-CIT displayed improvements in functional capacities (P < 0.05), total (mean ± SD: HIIT-PLA: +1.27 ± 3.19%, HIIT-CIT: +1.05 ± 2.91%, P < 0.05) and leg lean mass (HIIT-PLA: +1.62 ± 3.85%, HIIT-CIT: +1.28 ± 4.82%, P < 0.05), waist circumference (HIIT-PLA: -2.2 ± 2.9 cm, HIIT-CIT: -2.6 ± 2.5 cm, P < 0.05), and muscle power (HIIT-PLA: +15.81 ± 18.02%, HIIT-CIT: +14.62 ± 20.02%, P < 0.05). Only HIIT-CIT decreased fat mass (-1.04 ± 2.42%, P < 0.05) and increased handgrip and quadriceps strength (+4.28 ± 9.36% and +10.32 ± 14.38%, respectively, P < 0.05). Both groups increased markers of muscle mitochondrial content, mitochondrial fusion, and mitophagy (P < 0.05). Only HIIT-CIT decreased the expression of the lipid droplet-associated protein CIDEA (P < 0.001). CONCLUSIONS: High-intensity interval training is effective in improving functional capacities, lean mass, muscle power, and waist circumference in obese older adults. HIIT also increases markers of mitochondrial biogenesis, mitochondrial fusion, and mitophagy. Importantly, adding CIT to HIIT results in a greater increase in muscle strength and a significant decrease in fat mass. The present study therefore positions HIIT combined with CIT as an effective intervention to improve the health status of obese older adults.

Study of the Kinetics of the Determinants of Performance During a Mountain Ultramarathon: Multidisciplinary Protocol of the First Trail Scientifique de Clécy 2021.

BACKGROUND: The growing interest of the scientific community in trail running has highlighted the acute effects of practice at the time of these races on isolated aspects of physiological and structural systems; biological, physiological, cognitive, and muscular functions; and the psychological state of athletes. However, no integrative study has been conducted under these conditions with so many participants and monitoring of pre-, per-, and postrace variables for up to 10 days over a distance close to 100 miles. OBJECTIVE: The aim of this study was to evaluate the kinetics of the performance parameters during a 156 km trail run and 6000 m of elevation gain in pre-, per-, and postrace conditions. The general hypothesis is based on significant alterations in the psychological, physiological, mechanical, biological, and cognitive parameters. METHODS: The Trail Scientifique de Clécy took place on November 11, 2021. This prospective experimental study provides a comprehensive exploration of the constraints and adaptations of psychophysiological and sociological variables assessed in real race conditions during a trail running of 156 km on hilly ground and 6000 m of elevation gain (D+). The study protocol allowed for repeatability of study measurements under the same experimental conditions during the race, with the race being divided into 6 identical loops of 26 km and 1000 m D+. Measurements were conducted the day before and the morning of the race, at the end of each lap, after a pit stop, and up to 10 days after the race. A total of 55 participants were included, 43 (78%) men and 12 (22%) women, who were experienced in ultra-trail-running events and with no contraindications to the practice of this sport. RESULTS: The launch of the study was authorized on October 26, 2021, under the trial number 21-0166 after a favorable opinion from the Comité de Protection des Personnes Ouest III (21.09.61/SIRIPH 2G 21.01586.000009). Of the 55 runners enrolled, 41 (75%) completed the race and 14 (25%) dropped out for various reasons, including gastric problems, hypothermia, fatigue, and musculoskeletal injuries. All the measurements for each team were completed in full. The race times (ie, excluding the measurements) ranged from 17.8206 hours for the first runner to 35.9225 hours for the last runner. The average time to complete all measurements for each lap was 64 (SD 3) minutes. CONCLUSIONS: The Trail Scientifique de Clécy, by its protocol, allowed for a multidisciplinary approach to the discipline. This approach will allow for the explanation of the studied parameters in relation to each other and observation of the systems of dependence and independence. The initial results are expected in June 2022. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR1-10.2196/38027.