Tangeretin Enhances Muscle Endurance and Aerobic Metabolism in Mice via Targeting AdipoR1 to Increase Oxidative Myofibers.

Slow oxidative myofibers play an important role in improving muscle endurance performance and maintaining body energy homeostasis. However, the targets and means to regulate slow oxidative myofibers proportion remain unknown. Here, we show that tangeretin (TG), a natural polymethoxylated flavone, significantly activates slow oxidative myofibers-related gene expression and increases type I myofibers proportion, resulting in improved endurance performance and aerobic metabolism in mice. Proteomics, molecular dynamics, cellular thermal shift assay (CETSA) and drug affinity responsive target stability (DARTS) investigations revealed that TG can directly bind to adiponectin receptor 1 (AdipoR1). Using AdipoR1-knockdown C2C12 cells and muscle-specific AdipoR1-knockout mice, we found that the positive effect of TG on regulating slow oxidative myofiber related markers expression is mediated by AdipoR1 and its downstream AMPK/PGC-1α pathway. Together, our data uncover TG as a natural compound that regulates the identity of slow oxidative myofibers via targeting the AdipoR1 signaling pathway. These findings further unveil the new function of TG in increasing the proportion of slow oxidative myofibers and enhancing skeletal muscle performance.

Systemic Deletion of ARRDC4 Improves Cardiac Reserve and Exercise Capacity in Diabetes.

BACKGROUND: Exercise intolerance is an independent predictor of poor prognosis in diabetes. The underlying mechanism of the association between hyperglycemia and exercise intolerance remains undefined. We recently demonstrated that the interaction between ARRDC4 (arrestin domain-containing protein 4) and GLUT1 (glucose transporter 1) regulates cardiac metabolism. METHODS: To determine whether this mechanism broadly impacts diabetic complications, we investigated the role of ARRDC4 in the pathogenesis of diabetic cardiac/skeletal myopathy using cellular and animal models. RESULTS: High glucose promoted translocation of MondoA into the nucleus, which upregulated Arrdc4 transcriptional expression, increased lysosomal GLUT1 trafficking, and blocked glucose transport in cardiomyocytes, forming a feedback mechanism. This role of ARRDC4 was confirmed in human muscular cells from type 2 diabetic patients. Prolonged hyperglycemia upregulated myocardial Arrdc4 expression in multiple types of mouse models of diabetes. We analyzed hyperglycemia-induced cardiac and skeletal muscle abnormalities in insulin-deficient mice. Hyperglycemia increased advanced glycation end-products and elicited oxidative and endoplasmic reticulum stress leading to apoptosis in the heart and peripheral muscle. Deletion of Arrdc4 augmented tissue glucose transport and mitochondrial respiration, protecting the heart and muscle from tissue damage. Stress hemodynamic analysis and treadmill exhaustion test uncovered that Arrdc4-knockout mice had greater cardiac inotropic/chronotropic reserve with higher exercise endurance than wild-type animals under diabetes. While multiple organs were involved in the mechanism, cardiac-specific overexpression using an adenoassociated virus suggests that high levels of myocardial ARRDC4 have the potential to contribute to exercise intolerance by interfering with cardiac metabolism through its interaction with GLUT1 in diabetes. Importantly, the ARRDC4 mutation mouse line exhibited greater exercise tolerance, showing the potential therapeutic impact on diabetic cardiomyopathy by disrupting the interaction between ARRDC4 and GLUT1. CONCLUSIONS: ARRDC4 regulates hyperglycemia-induced toxicities toward cardiac and skeletal muscle, revealing a new molecular framework that connects hyperglycemia to cardiac/skeletal myopathy to exercise intolerance.

Comparative effectiveness of eHealth interventions on the exercise endurance and quality of life of patients with COPD: A systematic review and network meta-analysis.

AIMS: To compare the effectiveness of different types of eHealth interventions in improving exercise endurance and quality of life in chronic obstructive pulmonary disease (COPD) patients. BACKGROUND: COPD is a chronic airway disease characterized by persistent respiratory symptoms and airflow limitation. eHealth interventions have been accepted and recognized by healthcare professionals and COPD patients as an effective alternative to pulmonary rehabilitation. However, it is not clear which eHealth interventions are effective and preferred for exercise endurance and quality of life in COPD patients. DESIGN: A systematic review and network meta-analysis based on PRISMA-NMA. METHODS: We searched nine electronic databases to identify randomized controlled trials addressing the effect of eHealth interventions on the exercise endurance and quality of life of COPD patients from their inception to 30 October 2022. First, a random-effects model was chosen to conduct a traditional meta-analysis to directly investigate the efficacy of different eHealth interventions. Next, a network meta-analysis was performed to evaluate the relative efficacy of the eHealth interventions for COPD. The quality of the data was assessed using the Cochrane Risk of Bias tool. RESULTS: Fifty-one studies containing six eHealth interventions (telemonitoring, application [APP], web-based interventions, phone calls, virtual reality and combined interventions [≥two types]) were included in the final analysis. Network meta-analysis showed that telemonitoring, APP, web-based interventions and combined interventions improved exercise endurance in COPD patients, with telemonitoring being the most effective. Web-based interventions and apps are effective in improving the quality of life, and web-based interventions are the most effective. CONCLUSIONS: This study confirms that eHealth interventions can improve exercise endurance and quality of life in COPD patients. In the future, healthcare professionals can promote the use of telemedicine in COPD patients to enhance their exercise endurance and quality of life according to their individual needs. RELEVANCE TO CLINICAL PRACTICE: This evidence suggests that eHealth interventions can improve exercise endurance and quality of life in COPD patients. Therefore, in the future, eHealth interventions could be used to maximize their effectiveness in improving exercise endurance and quality of life in COPD patients.

Effects of running with surgical masks on cardiopulmonary function in healthy male university students.

[Purpose] In Japan, one measure against the novel coronavirus disease-2019 infection involves the public use of surgical masks. Research indicates that exercising while wearing a mask increases the physical burden, particularly affecting young people during high-intensity exercise. This study examined the effects of wearing masks while running in male university students. [Participants and Methods] The participants were 20 healthy male university students (21.6 ± 1.6 years). The participants underwent cardiopulmonary exercise tests with the masks on and off on different days until exhaustion. The following parameters were measured: exercise duration, Borg Scale rating (respiratory or lower extremities), surface temperature around the mouth, time to sweat onset, metabolic reaction, pulmonary ventilation, and cardiovascular reaction parameters. [Results] The results showed that VO2 max remained consistent between the mask-on and mask-off conditions. However, minute ventilation, respiratory rate, and heart rate decreased in the mask-on condition, which correlated with a reduction in exercise duration. Furthermore, running with the mask significantly decreased the VE/VO2, VE/ VO2, Borg Scale rating of the lower extremities, and the time to sweat onset. [Conclusion] Running with a surgical mask affected respiratory function and decreased exercise duration in healthy male university students. However, it did not induce any changes in VO2 max.

Validity and reliability of the 2-min step test in individuals with stroke and lower-limb musculoskeletal disorders.

Introduction: We investigated the reliability and validity of the 2-min step test (2MST) for assessing the exercise endurance of individuals with stroke and lower-limb musculoskeletal disorders. Participants and methods: The participants were 39 individuals with stroke and 42 with lower-limb musculoskeletal disorders (mainly hip fractures) from the convalescent rehabilitation wards of four hospitals. The concurrent validity and congruence between the 2MST and the 6-min walk test (6MWT) and construct validity by hypotheses testing, including mobility and lower limb muscle strength, were also confirmed. A subset of participants (stroke-group, n = 15; musculoskeletal-group, n = 19) underwent a retest 2MST for our evaluation of relative and absolute reliability using the intraclass correlation coefficient (ICC1,1) and Bland-Altman plot. Results: Both groups showed a moderate correlation between the 2MST and 6MWT (ρ = 0.55-0.60), but the congruence was not sufficient. The 6MWT was correlated with mobility in both groups and with muscle strength in the stroke group, whereas the 2MST did not show a significant correlation with mobility. The relative reliability was excellent in both groups (ICC1,1 > 0.9). In terms of absolute reliability, the width of the limit of agreement was 18.8% for the stroke group and 15.4% for the musculoskeletal group, relative to their respective sample means of 2MST. A fixed bias was identified in the stroke group, in which step counts increased by 6.5 steps upon retesting. Discussion: Our analyses revealed that the 2MST is a valid and reliable tool for assessing the exercise endurance of individuals with stroke or lower-limb musculoskeletal disorders. However, it is necessary to validate the absolute reliability observed herein by using a larger sample size. In addition, when assessing the exercise endurance of individuals with stroke, it may be necessary to consider the potential bias of an increased step count during retesting.

Neuronal E93 is required for adaptation to adult metabolism and behavior.

OBJECTIVE: Metamorphosis is a transition from growth to reproduction, through which an animal adopts adult behavior and metabolism. Yet the neural mechanisms underlying the switch are unclear. Here we report that neuronal E93, a transcription factor essential for metamorphosis, regulates the adult metabolism, physiology, and behavior in Drosophila melanogaster. METHODS: To find new neuronal regulators of metabolism, we performed a targeted RNAi-based screen of 70 Drosophila orthologs of the mammalian genes enriched in ventromedial hypothalamus (VMH). Once E93 was identified from the screen, we characterized changes in physiology and behavior when neuronal expression of E93 is knocked down. To identify the neurons where E93 acts, we performed an additional screen targeting subsets of neurons or endocrine cells. RESULTS: E93 is required to control appetite, metabolism, exercise endurance, and circadian rhythms. The diverse phenotypes caused by pan-neuronal knockdown of E93, including obesity, exercise intolerance and circadian disruption, can all be phenocopied by knockdown of E93 specifically in either GABA or MIP neurons, suggesting these neurons are key sites of E93 action. Knockdown of the Ecdysone Receptor specifically in MIP neurons partially phenocopies the MIP neuron-specific knockdown of E93, suggesting the steroid signal coordinates adult metabolism via E93 and a neuropeptidergic signal. Finally, E93 expression in GABA and MIP neurons also serves as a key switch for the adaptation to adult behavior, as animals with reduced expression of E93 in the two subsets of neurons exhibit reduced reproductive activity. CONCLUSIONS: Our study reveals that E93 is a new monogenic factor essential for metabolic, physiological, and behavioral adaptation from larval behavior to adult behavior.

Effect of a Ventilatory Assist Device in Addition to Supplemental Oxygen on Exercise Endurance in Subjects With COPD.

BACKGROUND: This study assessed the clinical effects of a ventilatory assist (VA) device in addition to supplemental O2 (VA+O2) on exercise endurance in subjects with severe to very severe COPD managed with long-term oxygen therapy (LTOT). METHODS: This was a crossover clinical feasibility study of the effects of VA+O2 in subjects with severe to very severe COPD managed with LTOT (N = 15). At visit 1, physiologic measures were obtained, and subjects were tested on the cycle ergometer with VA. Peak work rate and flow for continuous supplemental O2/VA+O2 were established. At visit 2, subjects exercised at a constant work rate of 80% peak work rate to maximum endurance after allocation to VA+O2 or O2. Cardiorespiratory variables, work rate, and dyspnea were included to define potential clinical benefits of VA+O2. Data were analyzed using a linear mixed model. RESULTS: Fifteen subjects with COPD (mean ± SD, age 67.9 ± 9.0 y, FEV1 0.89 ± 0.35 observed) completed the study. Exercise duration in minutes was significantly longer with VA+O2 versus O2 (least squares mean [standard error], 12.0 [2.0] vs 6.2 [2.0], P = .01). VA+O2 versus O2 was also associated with significantly greater isotime improvements in Borg dyspnea scores (3.6 [0.5] vs 5.7 [0.5], P < .001), SpO2 (96.9 [0.9] vs 91.4 [0.9], P < .001), leg fatigue scores (3.8 [0.6] vs 5.2 [0.6], P = .008), and breathing frequency (22.8 [0.9] vs 25.8 [0.9] breaths/min, P = .01). There were no differences in heart rate. CONCLUSIONS: In symptomatic subjects with severe to very severe COPD, VA+O2 significantly increased exercise time and improved dyspnea, SpO2 , breathing frequency, and leg fatigue versus O2 alone.

Application evaluation of cardiopulmonary exercise test to guide comprehensive pulmonary rehabilitation in patients with pneumoconiosis / 环境与职业医学

Background At present, the practice of pulmonary rehabilitation for pneumoconiosis in China is in a primary stage. The basis for formulating an individualized comprehensive pulmonary rehabilitation plan is still insufficient, which is one of the factors limiting the development of community-level rehabilitation work. Objective To formulate an exercise prescription based on maximum heart rate measured by cardiopulmonary exercise test (CPET), conduct an individualized comprehensive pulmonary rehabilitation program with the exercise prescription for patients with stable pneumoconiosis, and evaluate its role in improving exercise endurance and quality of life, thus provide a basis for the application and promotion of pulmonary rehabilitation. Methods A total of 68 patients were recruited from the Occupational Disease Prevention Hospital of Jinneng Holding Coal Industry Group Co., Ltd. from April to August 2022 , and were divided into an intervention group and a control group by random number table method, with 34 cases in each group. All the pneumoconiosis patients participated in a baseline test. The control group was given routine drug treatment, while the intervention group received multidisciplinary comprehensive pulmonary rehabilitation treatment on the basis of routine drug treatment, including health education, breathing training, exercise training, nutrition guidance, psychological intervention, and sleep management, whose exercise intensity was determined according to the maximum heart rate provided by CPET. The rehabilitation training lasted for 24 weeks. Patients were evaluated at registration and the end of study respectively. CPET was used to measure peak oxygen uptake per kilogram (pVO2/kg), anaerobic threshold (AT), carbon dioxide equivalent of ventilation (EqCO2), maximum metabolic equivalent (METs), and maximum work (Wmax). The modified British Medical Research Council Dyspnea Questionnaire (mMRC), Self-rating Anxiety Scale (SAS), Self-rating Depression Scale (SDS), Pittsburgh Sleep Quality Index (PSQI), Chronic Obstructive Pulmonary Disease Assessment Test (CAT), and Short Form of Health Survey (SF-36) were used to evaluate the potential effect of the comprehensive pulmonary rehabilitation program. Results Among the included 68 patients, 63 patients were having complete data, then 31 cases were assigned in the control group and 32 cases in the interventional group. Before the intervention, there was no significant difference in pVO2/kg, AT, EqCO2, METs, or Wmax between the two groups (P>0.05). At the end of the trail, the indicators like pVO2/kg [(19.81±2.38) mL·(min·kg)−1], AT [(14.48±2.33) mL·(min·kg)−1], METs (5.64±0.69), and Wmax [(85.25±14) W] of patients in the intervention group were all higher than those [(13.90±2.37) mL·(min·kg)−1, (11.70±1.94) mL·(min kg)−1, (3.97±0.70), and (61.77±14.72) W, respectively] in the control group (P<0.001); there was no significant difference in EqCO2 between the two groups (P=0.083). Before the trial, there was no significant difference in mMRC, SAS, SDS, PSQI, or CAT scores between the two groups (P>0.05). At the end of the trail, the mMRC score (1.16±0.57), SAS score (27.93±2.12), SDS score (26.48±1.44), PSQI score (1.08±0.88), and CAT score (4.34±3.28) of patients in the intervention group were lower than those [(2.03±0.83), (35.87±6.91), (34.23±6.65), (5.37±3.03), and (13.87±7.53), respectively] in the control group (P<0.001). The SF-36 scores of bodily pain (94.13±10.72), general health (87.50±5.68), vitality (95.31±5.53), mental health (99.88±0.71), and health changes (74.22±4.42) in the intervention group were higher than those [(71.87±32.72), (65.81±15.55), (74.52±16.45), (86.97±16.56), and (29.84±13.50), respectively] in the control group (P<0.001), and no significant difference was found in social functioning and role emotional scores (P>0.05). Conclusion Comprehensive pulmonary rehabilitation can increase the oxygen intake and exercise endurance of pneumoconiosis patients, ameliorate dyspnea symptoms, elevate psychological state and sleep quality, and improve the quality of life.

Validation of Constant Work Rate Cycling Endurance Time for Use in Chronic Obstructive Pulmonary Disease Clinical Trials.

Rationale: A COPD Foundation working group sought to identify measures of exercise endurance, a meaningful aspect of physical functioning in everyday life among patients with chronic obstructive pulmonary disease (COPD) that is not fully accepted in regulatory decision making, hampering drug development. Objectives: To demonstrate, as we previously asserted (Casaburi COPD 2022;9:252), that constant work rate cycling endurance time is an appropriate exercise endurance measure in patients with COPD. Methods: To validate this assertion, we assembled an integrated database of endurance time responses, including 8 bronchodilator (2,166 subjects) and 15 exercise training (3,488 subjects) studies (Casaburi COPD 2022;9:520). Results: Construct validity was demonstrated: 1) peak physiologic and perceptual responses were similar for constant work rate and incremental cycling; 2) after bronchodilator therapy, there were greater increases in endurance time in patients with more severe airflow limitation; 3) after exercise training, endurance time increases were similar across airflow limitation severities; and 4) there were correlations between changes in endurance time and changes in mechanistically related physiologic and perceptual variables. Test-retest reliability was demonstrated, with consistency of changes in endurance time at two time points after the intervention. Responsiveness was confirmed, with significant increases in endurance time after active (but not placebo) bronchodilator therapy, with greater increases seen with more severe airflow limitation and after exercise training. On the basis of regression analysis using multiple anchor variables, the minimum important difference for endurance time increase is estimated to be approximately 1 minute. Conclusions: Constant work rate cycling endurance time is a valid exercise endurance measure in COPD, suitable for contributing to the evaluation of treatment benefit supporting regulatory decision making and evidence-based therapeutic recommendations.

The Synergistic Effect of Quince Fruit and Probiotics (Lactobacillus and Bifidobacterium) on Reducing Oxidative Stress and Inflammation at the Intestinal Level and Improving Athletic Performance during Endurance Exercise.

Endurance exercise promotes damage at the intestinal level and generates a variety of symptoms related to oxidative stress processes, inflammatory processes, microbiota dysbiosis, and intestinal barrier damage. This study evaluated the effects of quince (Cydonia oblonga Mill.) and probiotics of the genera Lactobacillus and Bifidobacterium on intestinal protection and exercise endurance in an animal swimming model. Phytochemical characterization of the quince fruit demonstrated a total dietary fiber concentration of 0.820 ± 0.70 g/100 g and a fiber-bound phenolic content of 30,218 ± 104 µg/g in the freeze-dried fruit. UPLC-PDA-ESI-QqQ analyses identified a high content of polyphenol, mainly flavanols, hydroxycinnamic acids, hydroxybenzoic acids, flavonols, and, to a lesser extent, dihydrochalcones. The animal model of swimming was performed using C57BL/6 mice. The histological results determined that the consumption of the synbiotic generated intestinal protection and increased antioxidant (catalase and glutathione peroxidase enzymes) and anti-inflammatory (TNF-α and IL-6 and increasing IL-10) activities. An immunohistochemical analysis indicated mitochondrial biogenesis (Tom2) at the muscular level related to the increased swimming performance. These effects correlated mainly with the polyphenol content of the fruit and the effect of the probiotics. Therefore, this combination of quince and probiotics could be an alternative for the generation of a synbiotic product that improves exercise endurance and reduces the effects generated by the practice of high performance sports.

Effectiveness and safety of opioids on breathlessness and exercise endurance in patients with chronic obstructive pulmonary disease: A systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: Opioids are recommended to treat advanced refractory dyspnoea despite optimal therapy by the American Thoracic Society clinical practice guidelines, while newly published randomised controlled trials of opioids in chronic obstructive pulmonary disease yield conflicting results. AIM: This study aimed to evaluate the effectiveness and safety of opioids for patients with chronic obstructive pulmonary disease. DESIGN: Systematic review and meta-analysis (PROSPERO CRD42021272556). DATA SOURCES: Databases of PubMed, EMBASE and CENTRAL were searched from inception to 2022 for eligible randomised controlled trials. RESULTS: Twenty-four studies including 975 patients, were included. In cross-over studies, opioids improved breathlessness (standardised mean difference, -0.43; 95% CI, -0.55 to -0.30; I2 = 18%) and exercise endurance (standardised mean difference, 0.22; 95% CI, 0.02-0.41; I2 = 70%). However, opioids failed to improve dyspnoea (standardised mean difference, -0.02; 95% CI, -0.22 to 0.19; I2 = 39%) and exercise endurance (standardised mean difference, 0.00; 95% CI, -0.27 to 0.27; I2 = 0%) in parallel control studies that administered sustained-release opioids for more than 1 week. The opioids used in most crossover studies were short-acting and rarely associated with serious adverse effects. Only minor side effects such as dizziness, nausea, constipation and vomiting were identified for short-acting opioids. CONCLUSIONS: Sustained-release opioids did not improve dyspnoea and exercise endurance. Short-acting opioids appeared to be safe, have potential to lessen dyspnoea and improve exercise endurance, supporting benefit in managing episodes of breathlessness and providing prophylactic treatment for exertional dyspnoea.

The effects of inorganic nitrate supplementation on exercise economy and endurance capacity across the menstrual cycle.

Oral inorganic nitrate (NO3-) supplementation has been shown to increase bioavailable NO and provide potential ergogenic benefits in males; however, data in females is scarce. Estrogen is known to increase endogenous NO bioavailability and to fluctuate throughout the menstrual cycle (MC), being lowest in the early follicular (EF) phase and highest during the late follicular (LF) phase. This study examined the effects of oral NO3- supplementation on exercise economy, endurance capacity, and vascular health in young females across the MC. Ten normally menstruating females' MCs were tested in a double-blinded, randomized design during both the EF and LF phases of the MC. Participants consumed ∼13 mmol NO3-, in the form of 140 mL beetroot juice (BRJ) or an identical NO3--depleted placebo (PL) for ∼3 days before lab visits and 2 h before testing on lab visits. Plasma nitrate, nitrite, and estradiol were assessed, as was blood pressure and pulse wave velocity. Moderate-intensity exercise economy and severe intensity time to exhaustion (TTE) were tested on a cycle ergometer. As expected, plasma estradiol was elevated in the LF phase, and plasma nitrite and nitrate were elevated in the BRJ condition. Exercise economy was unaltered by BRJ or the MC, however TTE was significantly worsened by 48 s (∼10%) after BRJ supplementation (P = 0.04), but was not different across the MC with no interaction effects. In conclusion, NO3- supplementation did not affect exercise economy or vascular health and worsened aerobic endurance capacity (TTE), suggesting healthy females should proceed with caution when considering supplementation with BRJ.NEW & NOTEWORTHY Although inorganic nitrate (NO3-) supplementation has increased in popularity as a means of improving exercise performance, data in females at different phases of the menstrual cycle are lacking despite known interactions of estrogen with NO. This study revealed neither NO3- supplementation nor the menstrual cycle influenced exercise economy or vascular health in healthy young naturally menstruating females, while NO3- supplementation significantly worsened endurance capacity (10%) independent of the menstrual cycle phase.

Energy constraint and compensation: Insights from endurance athletes.

The Constrained Model of Total Energy Expenditure predicts that increased physical activity may not influence total energy expenditure, but instead, induces compensatory energetic savings in other processes. Much remains unknown, however, about concepts of energy expenditure, constraint and compensation in different populations, and it is unclear whether this model applies to endurance athletes, who expend very large amounts of energy during training and competition. Furthermore, it is well-established that some endurance athletes consciously or unconsciously fail to meet their energy requirements via adequate food intake, thus exacerbating the extent of energetic stress that they experience. Within this review we A) Describe unique characteristics of endurance athletes that render them a useful model to investigate energy constraints and compensations, B) Consider the factors that may combine to constrain activity and total energy expenditure, and C) Describe compensations that occur when activity energy expenditure is high and unmet by adequate energy intake. Our main conclusions are as follows: A) Higher activity levels, as observed in endurance athletes, may indeed increase total energy expenditure, albeit to a lesser degree than may be predicted by an additive model, given that some compensation is likely to occur; B) That while a range of factors may combine to constrain sustained high activity levels, the ability to ingest, digest, absorb and deliver sufficient calories from food to the working muscle is likely the primary determinant in most situations and C) That energetic compensation that occurs in the face of high activity expenditure may be primarily driven by low energy availability i.e., the amount of energy available for all biological processes after the demands of exercise have been met, and not by activity expenditure per se.

Intermittent Fasting Sustainably Improves Glucose Tolerance in Normal Weight Male Mice Through Histone Hyperacetylation.

To explore the mechanism by which intermittent fasting (IF) exerts prolonged effects after discontinuation, we examined mice that had been subjected to 4 cycles of fasting for 72 hours and ad libitum feeding for 96 hours per week (72hIF), followed by 4 weeks of ad libitum feeding, focusing on expression of genes for lipid metabolism in the skeletal muscle and histone acetylation in the promoter region. The 72hIF regimen resulted in metabolic remodeling, characterized by enhanced lipid utilization and mitochondrial activation in the muscle. This long-term IF (72hIF) caused stronger metabolic effects than alternate day fasting (24hIF) wherein fasting and refeeding are repeated every 24 hours. Upregulation of lipid oxidation genes and an increase in oxygen utilization were sustained even at 4 weeks after discontinuation of 72hIF, associated with histone hyperacetylation of the promoter region of uncoupling protein 3 (Ucp3) and carnitine palmitoyl transferase 1b (Cpt1b) genes. An increase in leucine owing to fasting-induced muscle degradation was suggested to lead to the histone acetylation. These findings support the previously unappreciated notion that sustainable promotion of histone acetylation in lipid oxidation genes of the muscle and adipose tissues during and after IF may contribute to sustained metabolic effects of IF.

Effects of Probiotic Supplementation on Exercise and the Underlying Mechanisms.

Long-term, high-intensity exercise can trigger stress response pathways in multiple organs, including the heart and lungs, gastrointestinal tract, skeletal muscle, and neuroendocrine system, thus affecting their material and energy metabolism, immunity, oxidative stress, and endocrine function, and reducing exercise function. As a natural, safe, and convenient nutritional supplement, probiotics have been a hot research topic in the field of biomedical health in recent years. Numerous studies have shown that probiotic supplementation improves the health of the body through the gut-brain axis and the gut-muscle axis, and probiotic supplementation may also improve the stress response and motor function of the body. This paper reviews the progress of research on the role of probiotic supplementation in material and energy metabolism, intestinal barrier function, immunity, oxidative stress, neuroendocrine function, and the health status of the body, as well as the underlying mechanisms.

Inspiratory muscle training improves cardiopulmonary function in patients after transcatheter aortic valve replacement: a randomized clinical trial.

AIMS: Inspiratory muscle training (IMT) can increase the strength or endurance of the diaphragm and accessory muscles of inspiration, yet there is no evidence that endorses the role of IMT in patients of transcatheter aortic valve replacement (TAVR). This study for the first time tested the effects of IMT plus usual cardiac rehabilitation (CR) function in patients after TAVR. METHODS AND RESULTS: A double-blinded, randomized controlled, single-centre clinical trial was undertaken. Participants who had a confirmed diagnosis of valve heart disease and were clinically stable after TAVR were recruited and received a CR programme during the hospital stay. A total of 96 patients were recruited and randomly assigned to the IMT + CR group (n = 48) or the CR group (n = 48) in a 1:1 ratio. The group difference in the primary outcome, the 6-min walk distance at the discharge of the hospital, significantly favoured the IMT + CR group (mean difference -33.52, 95% CI: -64.42 to -2.62, P = 0.034). The significant difference was maintained at the 1-month and 3-month follow-ups (mean difference: 41.51, 95% CI: 1.82-81.21, P = 0.041). In addition, the mean hospital stays of subjects in the IMT + CR group was 11 days, which was significantly shorter than the 12.5 days in the CR group (P = 0.016). Sensitivity analysis using per-protocol analysis supported these findings. No adverse treatment-related events were reported. CONCLUSION: Compared with usual CR, IMT plus CR can effectively improve exercise endurance, pulmonary ventilation function, and inspiratory muscle strength in patients after TAVR and shorten the length of hospital stay.

Hydrogen improves exercise endurance in rats by promoting mitochondrial biogenesis.

BACKGROUND: Previous studies have shown that hydrogen water has antioxidant and anti-inflammatory effects on exercise-induced fatigue; however, its molecular mechanism remains unclear. METHODS: Adult male Sprague-Dawley rats were randomly divided into a pure water drinking group (NC) and a hydrogen water drinking group (HW) (n = 7), and 2-week treadmill training was used to establish a sports model. Gut bacterial community profiling was performed using 16S rRNA gene sequencing analysis. The expression levels of mitochondrial energy metabolism-related genes and the levels of sugar metabolites and enzymes were measured. RESULTS: The exercise tolerance of rats in the HW group significantly improved, and the distribution and diversity of intestinal microbes were altered. Hydrogen significantly upregulated genes related to mitochondrial biogenesis, possibly via the Pparγ/Pgc-1α/Tfam pathway. In addition, hydrogen effectively mediated the reprogramming of skeletal muscle glucose metabolism. CONCLUSION: Our findings establish a critical role for hydrogen in improving endurance exercise performance by promoting mitochondrial biogenesis via the Pparγ/Pgc-1α/Tfam pathway.

Supplementation with Vitis vinifera Jingzaojing Leaf and Shoot Extract Improves Exercise Endurance in Mice.

Switching myofibers from the fast-glycolytic type to the slow-oxidative type is associated with an alleviation of the symptoms associated with various cardiometabolic diseases. This study investigates the effect of Vitis vinifera Jingzaojing leaf and shoot extract (JLSE), which is rich in phenolic compounds, on the regulation of skeletal muscle fiber-type switching, as well as the associated underlying mechanism. Male C57BL/6N mice were supplemented orally with vehicle or JLSE (300 mg/kg) and subjected to treadmill exercise training. After four weeks, mice in the JLSE-supplemented group showed significantly improved exercise endurance and mitochondrial oxidative capacity. JLSE supplementation increased the expression of sirtuin 6 and decreased Sox6 expression, thereby elevating the number of mitochondria and encouraging fast-to-slow myofiber switching. The results of our experiments suggest that JLSE supplementation reprograms myofiber composition to favor the slow oxidative type, ultimately enhancing exercise endurance.

Endurance Time During Constant Work Rate Cycle Ergometry in COPD: Development of an Integrated Database From Interventional Studies.

Introduction: The COPD Biomarkers Qualification Consortium (CBQC) was formed under COPD Foundation management, with the goal of qualifying biomarkers and clinical outcome assessments through established regulatory processes for chronic obstructive pulmonary disease (COPD). Within CBQC, a working group evaluated opportunities for qualification of an exercise endurance measure. In a recent publication (Chronic Obstr Pulm Dis. 2022; 9[2]:252-265), we described a conceptual framework establishing exercise endurance's direct relationship to an individual with COPD's experience of physical functioning in daily life, and that increase in exercise endurance is a patient-centered, meaningful treatment benefit. We further proposed endurance time during constant work rate cycle ergometery (CWRCE) as a useful efficacy endpoint in clinical therapeutic intervention trials. In this current publication, we describe the process of assembling an integrated database of endurance time responses to interventions in COPD. Methods: We sought participant-level data from published studies incorporating CWRCE as an outcome measure. A literature search screened 2993 publications and identified 553 studies for assessment. Two interventions had sufficient data across studies to warrant data extraction: bronchodilators and rehabilitative exercise training. Investigators were contacted and requested to provide participant-by-participant data from their published studies. Results: The final dataset included data from 8 bronchodilator studies (2166) participants and 15 exercise training studies (3488 participants). The database includes 71 variables per participant, comprising demographic, pulmonary function, and detailed physiologic response data. This paper provides a detailed description of the analysis population, while analysis supporting the validation/qualification process and addressing other scientific questions will be described in subsequent publications.

Ginsenoside Rf Enhances Exercise Endurance by Stimulating Myoblast Differentiation and Mitochondrial Biogenesis in C2C12 Myotubes and ICR Mice.

Ginsenoside Rf (G-Rf) is a saponin of the protopanaxatriol family and a bioactive component of Korean ginseng. Several ginsenosides are known to have a positive effect on exercise endurance, but there is not yet a report on that of G-Rf. Forced swimming tests were performed on G-Rf-treated mice to evaluate the effect of G-Rf on exercise endurance. Subsequently, the expression of markers related to myoblast differentiation and mitochondrial biogenesis in murine skeletal C2C12 myotubes and tibialis anterior muscle tissue was determined using Western blotting, quantitative real-time polymerase chain reaction, and immunofluorescence staining to elucidate the mechanism of action of G-Rf. The swimming duration of the experimental animal was increased by oral gavage administration of G-Rf. Moreover, G-Rf significantly upregulated the myoblast differentiation markers, mitochondrial biogenesis markers, and its upstream regulators. In particular, the mitochondrial biogenesis marker increased by G-Rf was decreased by each inhibitor of the upstream regulators. G-Rf enhances exercise endurance in mice, which may be mediated by myoblast differentiation and enhanced mitochondrial biogenesis through AMPK and p38 MAPK signaling pathways, suggesting that it increases energy production to satisfy additional needs of exercising muscle cells. Therefore, G-Rf is an active ingredient in Korean ginseng responsible for improving exercise performance.