Endurance Exercise Training Research Articles

Ventricular arrhythmias in association with athletic cardiac remodelling.

Athletes are predisposed to atrial arrhythmias but the association between intense endurance exercise training, ventricular arrhythmias (VAs) and sudden cardiac death is less well established. Thus, it is unclear whether the 'athlete's heart' promotes specific arrhythmias or whether it represents a more general pro-arrhythmogenic phenotype. Whilst direct causality has not been established, it appears possible that repeated exposure to high-intensity endurance exercise in some athletes contributes to formation of pro-arrhythmic cardiac phenotypes that underlie VAs. Theories regarding potential mechanisms for exercise-induced VAs include repeated bouts of myocardial inflammation and stretch-induced cellular remodelling. Small animal models provide some insights, but larger animal and human data are sparse. The current clinical approach to VAs in athletes is to differentiate those with and without structural or electrical heart disease. However, if the athlete's heart involves a degree of pro-arrhythmogenic remodelling, then this may not be such a simple dichotomy. Questions are posed by athletes with VAs in combination with extreme remodelling. Some markers, such as scar on magnetic resonance imaging, may point toward a less benign phenotype but are also quite common in ostensibly healthy athletes. Other clinical and invasive electrophysiology features may be helpful in identifying the at-risk athlete. This review seeks to discuss the association between athletic training and VAs. We will discuss the potential mechanisms, clinical significance and approach to the management of athletes with VAs.

Exercise improves muscle mitochondrial dysfunction-associated lipid profile under circadian rhythm disturbance.

We investigated whether endurance exercise training (EXT) ameliorates circadian rhythm (CR)-induced risk factors by improving skeletal muscle (SKM) mitochondrial biogenesis, reducing oxidative stress, and modulating apoptotic protein expression. We distinguished between regular and shift workers using the National Health and Nutrition Examination Survey (NHANES) and investigated the health problems caused by shift work (CR disturbance) and the potential therapeutic effects of exercise. In our animal study, 36 rats underwent 12 weeks of CR disturbance, divided into regular and irregular CR groups. These groups were further split into EXT (n = 12) and sedentary (n = 12) for an additional 8 weeks. We analyzed SKM tissue to understand the molecular changes induced by CR and EXT. NHANES data were analyzed using SAS 9.4 and Prism 8 software, while experimental animal data were analyzed using Prism 8 software. The statistical procedures used in each experiment are indicated in the figure legends. Our studies showed that CR disturbance increases dyslipidemia, alters circadian clock proteins (BMAL1, PER2), raises apoptotic protein levels, and reduces mitochondrial biogenesis in SKM. EXT improved LDL-C and HDLC levels without affecting muscle BMAL1 expression. It also enhanced mitochondrial biogenesis (AMPK, PGC-1α, Tfam, NADH-UO, COX-I), antioxidant levels (Catalase, SOD1, SOD2), and apoptotic protein (p53, Bax/Bcl2) expression or activity in SKM. We demonstrated that shift work-induced CR disturbance leads to dyslipidemia, diminished mitochondrial biogenesis, and reduced antioxidant capacity in SKM. However, EXT can counteract dyslipidemia under CR disturbance, potentially lowering the risk of cardiovascular disorders.

Physical activity habits among members of the Athens Medical Society in Greece

Abstract Introduction Benefits of regular physical activity and exercise are well documented. Healthcare workers play a crucial role in counseling and appropriately referring their patients to adopt physical activity. However, doctors’ exercise habits range between different medical specialties and health service infrastructure. Purpose In this study, we assess physicians’ exercise performance according to the recommendations of 2020 ESC Guidelines. Methods The population of this cross-sectional study comprised 742 physicians of the Athens Medical Society (AMS), Greece. The study instrument was a self-administered questionnaire mailed in October 2023 to investigate physicians’ exercise habits, baseline characteristics of population, specialty, and health service infrastructure [Greek National Healthcare System (GNHS) or Private Practice (PP)]. European Society of Cardiology (ESC) Guidelines recommend at least 150 min/week of moderate-intensity exercise in all healthy adults. Subjects were divided in two groups according to their compliance to ESC Guidelines: 1. Moderate-intensity endurance exercise training per week ≥ 150 min (Group A); 2. Moderate-intensity endurance exercise training per week <150 min (Group B). Results The recommended exercise training per week goal is achieved by the majority of AMS members (53.4%) with an estimated mean exercise endurance training time of 240 ± 285 minutes. Between Group A and Group B there was no difference in age (50±12years vs. 50±13years, p=0.73), whereas there was significant difference in male sex prevalence (58% vs. 43%, p <0.001), in Body Mass Index (24.7 ± 3.8 kg/m2 vs. 26.2 ± 4.7 kg/m2, p <0.001), in Smoking habits (17.4% vs. 23.5%, p=0.04), in diabetes mellitus incidence (6.6% vs. 11.8%, p= 0.01) and in the use of activity monitoring wearables (45.2% vs. 29.8%, p<0.001). Interestingly, there was significant difference between GNHS and PP doctors representation in Group A and B with more doctors in the PP categorized in the Group A (p=0.008) (Figure 1). Importantly, logistic regression analysis revealed that even after adjustment for the aforementioned confounders there was significant under-representation of the GNHS in the Group A or otherwise doctors in the GNHS have 33% decrease odds of achieving the recommended exercise training per week (Odds Ratio: 0.676, 95%CI 0.484, 0.943, p=0.02) (Table 1). Conclusion A significant proportion of the AMS members follows the recommended ESC guidelines for minimum exercise training per week. Several factors affect their adherence to exercise time recommendation. Interestingly, AMS doctors working on the GNHS independently of other factors are less adherent to exercise recommendations. These findings emphasize the need to strengthen prevention strategies to AMS.

Association between wearable activity trackers usage and levels of physical activity among Athens Medical Society members

Abstract Introduction Wearable Activity Trackers (WAT) provide real-time feedback on activity levels and play a pivotal role in fostering an active lifestyle. Moreover, WAT can encourage doctors’ awareness to be more conscious of their daily physical activity whose exercise habits range between different medical specialties. Purpose The aim of this study is to evaluate the influence of WAT usage on physicians’ exercise habits according to the recommendations of ESC Guidelines. Methods This cross-sectional study comprised 742 physicians of the Athens Medical Society (AMS), Greece. The study instrument was a self-administered questionnaire mailed in October 2023 to evaluate physicians’ usage of WAT, baseline characteristics of population, specialty, and physical exercise habits. European Society of Cardiology (ESC) Guidelines recommend at least 150 min/week of moderate-intensity exercise in all healthy adults. Subjects were divided in two groups according to their usage of WAT or not in their everyday life: 1. Daily usage of WAT (Group A); 2. No regular or even on usage of WAT (Group B). Results A considerably high proportion of the total population use WAT daily (38%). Between Group A and Group B there was no difference in age (49±12 years vs. 51±13 years, p=0.07), male sex prevalence (55% vs. 49%, p=0.08) and BMI (25.7± 4.6 kg/m2 vs. 25.2± 4.1 kg/m2, p=0.11). Interestingly, there was statistically significant difference in mean exercise endurance training time between Group A and Group B (301±304 min. vs. 209±268 min., p<0.001) (Figure 1) and in the proportion of the doctors who follow the ESC Recommendations (63.5% vs. 47.2%, p<0.001). Furthermore, most of the physicians who use WAT have awareness for ESC Guidelines (59% vs. 47%, p<0.001), and most of them apply diet to lose weight (36% vs. 29%, p=0.04). Finally, WAT were mostly used by 4 main specialties: Cardiology (47%), Endocrinology (44%), Surgery (35%) and Internal Medicine (25%), with cardiologists reporting the higher use (p=0.045). Conclusion This study underscores the widespread adoption of WAT among physicians, highlighting their potential to positively influence exercise habits and adherence to ESC Guidelines. Physicians using WAT demonstrated increased exercise endurance training time, greater awareness of ESC Guidelines, and a higher propensity to implement weight loss diets compared to non-users. Additionally, variations in WAT usage and awareness of ESC Guidelines across medical specialties emphasize the need for targeted interventions to promote physical activity and enhance overall health among healthcare professionals.

Effect of Endurance Exercise Training on Gut Microbiota and ER Stress

Regular exercise as part of one’s lifestyle is well-recognized for its beneficial effect on several diseases such as cardiovascular disease and obesity; however, many questions remain unanswered regarding the effects of exercise on the gut environment. This study aimed to investigate the impact of long-term endurance exercise on modulating inflammation and endoplasmic reticulum (ER) stress. Fifteen-week-old male Sprague-Dawley (SD) rats were subjected to six months of endurance treadmill training, while age-matched controls remained sedentary. Results showed that IL-6 mRNA levels in colon tissues were significantly higher in the exercise group compared to the sedentary group. Exercise activated a significant ER stress-induced survival pathway by increasing BiP and phosphorylation of eIF2α (p-eIF2α) expressions in the liver and colon, while decreasing CHOP in the liver. Gene expressions of MUC2, Occludin, and Claudin-2 were increased in the colon of the exercise group, indicating enhanced intestinal integrity. Furthermore, the data showed a positive correlation between microbiota α-diversity and BiP (r = 0.464~0.677, p < 0.05). Populations of Desulfovibrio C21 c20 were significantly greater in the exercise group than the sedentary group. Additionally, predicted functions of the gut microbial community in terms of enzymes and pathways supported the enhancement of fatty-acid-related processes by exercise. These findings suggest that prolonged endurance exercise can affect the colon environment, which is likely related to changes in inflammation, ER stress, mucin layers and tight junctions, associated with modifications in the gut microbiome.

12509 Identification Of Novel Exercise Training-induced Circulating Proteins: Hemostatic, Apoptotic, And Key Neuronal Factors

Abstract Disclosure: A. Shalit: None. M. Vamvini: None. P. Nigro: None. L.K. Simpson: None. H. Pan: None. J.M. Dreyfuss: None. L.J. Goodyear: Grant Recipient; Self; Daiichi Sankyo. R.J. Middelbeek: None. Exercise training induces a plethora of health benefits including improved glucose homeostasis, decreased cardiovascular disease, and improved cognitive function. An emerging concept is that many of these beneficial effects of exercise are mediated through the secretion of humoral factors into the blood. Identification of these exercise-regulated factors hold promise for novel treatments for disease. Here, we performed proteomic analysis to discover novel circulating factors in response to endurance exercise training in human participants. Given that nutritional status can affect the circulating proteome, another aim was to determine if proteomic adaptations to exercise training have similar effects under both fasted and random-fed conditions. Sedentary normoglycemic participants (3M/5F, age 22-41y) performed a supervised 10-week exercise training program, which by week 4 was 4x60 min exercise at 65-70% V̇O2peak. Fasted and random-sampling morning blood draws were collected pre-training and between 24-72 hours following the final training session. Proteomic detection was by SOMAscan. Exercise training significantly improved V̇O2peak by 17% (p=0.003). Out of 1,310 detected proteins, exercise training significantly changed 293 proteins in the fasted state and 360 proteins in the random-sampling state (p<0.05). Integration showed that 172 proteins were changed under both nutritional conditions (123 upregulated and 49 downregulated). Gene Set Enrichment Analysis (GSEA) of the commonly upregulated proteins showed that training resulted in enrichment in neuronal, hemostatic, and apoptotic pathways, whereas the downregulated proteins were enriched in neuronal and extracellular matrix processes. Since neuronal pathways were identified in both up and downregulated proteins, we focused our analysis there, identifying 31 upregulated and 4 downregulated neuronally-associated proteins. Importantly, exercise training reduced levels of CDK5, a protein that is hyperactivated in neurodegeneration and Alzheimer's disease. Moreover, GSTP1, a direct inhibitor of CDK5, along with downstream proteins inhibited by CDK5 (RAC1, STUB1, 14-3-3ε/YWHAE, HSP90AA1, CFL1), were significantly increased following exercise training.In conclusion, exercise training regulates circulating factors involved in neuronal, hemostatic, apoptotic, and extracellular matrix pathways, with these effects being independent of nutritional status. Our finding of exercise training-induced decreases in multiple proteins of the CDK5 pathway, a pathway whose downregulation is associated with neuroprotection, identify CDK5 as a novel and potentially important mediator of the beneficial effects of exercise training on cognitive function. Presentation: 6/1/2024

A partial loss-of-function variant (Ile191Val) of the TAS1R2 glucose receptor is associated with enhanced responses to exercise training in older adults with obesity: A translational study

BackgroundThe TAS1R2 receptor, known for its role in taste perception, has also emerged as a key regulator of muscle physiology. Previous studies have shown that genetic ablation of TAS1R2 in mice enhances muscle fitness mimicking responses to endurance exercise training. However, the translational relevance of these findings to humans remains uncertain. MethodsWe explored responses to endurance exercise training in mice and humans with genetic deficiency of TAS1R2. First, we assessed the effects of muscle-specific deletion of TAS1R2 in mice (mKO) or wild type controls (mWT) following 4 weeks of voluntary wheel running (VWR). Next, we investigated the effects of the TAS1R2-Ile191Val (rs35874116) partial loss-of-function variant on responses to a 6-month diet-induced weight loss with exercise training (WLEX), weight loss alone (WL), or education control (CON) interventions in older individuals with obesity. Participants were retrospectively genotyped for the TAS1R2-Ile191Val polymorphism and classified as conventional function (Ile/Ile) or partial loss-of-function (Val carriers: Ile/Val and Val/Val). Body composition, cardiorespiratory fitness, and skeletal muscle mitochondrial function were assessed before and after the intervention. ResultsIn response to VWR, mKO mice demonstrated enhanced running endurance and mitochondrial protein content. Similarly, TAS1R2 Val carriers exhibited distinctive improvements in body composition, including increased muscle mass, along with enhanced cardiorespiratory fitness and mitochondrial function in skeletal muscle following the WLEX intervention compared to Ile/Ile counterparts. Notably, every Val carrier demonstrated substantial responses to exercise training and weight loss, surpassing all Ile/Ile participants in overall performance metrics. ConclusionsOur findings suggest that TAS1R2 partial loss-of-function confers beneficial effects on muscle function and metabolism in humans in response to exercise training, akin to observations in TAS1R2 muscle-deficient mice. Targeting TAS1R2 may help enhancing exercise training adaptations in individuals with compromised exercise tolerance or metabolic disorders, presenting a potential avenue for personalized exercise interventions.

Exercise activates AMPK in mouse and human pancreatic islets to decrease senescence.

Beta (β)-cell senescence contributes to type 2 diabetes mellitus (T2DM). While exercise is vital for T2DM management and significantly affects cellular ageing markers, its effect on β-cell senescence remains unexplored. Here, we show that short-term endurance exercise training (treadmill running, 1 h per day for 10 days) in two male and female mouse models of insulin resistance decreases β-cell senescence. In vivo and in vitro experiments revealed that this effect is mediated, at least in part, by training-induced increases in serum glucagon, leading to activation of 5'-AMP-activated protein kinase (AMPK) signalling in β-cells. AMPK activation resulted in the nuclear translocation of NRF2 and decreased expression of senescence markers and effectors. Remarkably, human islets from male and female donors with T2DM treated with serum collected after a 10-week endurance exercise training programme showed a significant decrease in the levels of senescence markers. These findings indicate that exercise training decreases senescence in pancreatic islets, offering promising therapeutic implications for T2DM.

A Pilot Study on the Effects of Exercise Training on Cardiorespiratory Performance, Quality of Life, and Immunologic Variables in Long COVID.

Objectives: Fatigue is a prominent feature of long COVID (LC) and may be related to several pathophysiologic mechanisms, including immune hyperstimulation. Aerobic endurance exercise training may be a useful therapy, with appropriate attention to preventing post-exertional malaise. Methods: Fourteen participants completed a pilot study of aerobic exercise training (twenty 1.5 h sessions of over 10 weeks). Cardiorespiratory fitness, 6 min walk distance, quality of life, symptoms, 7-day physical activity, immunophenotype, and inflammatory biomarkers were measured before and after exercise training. Results: The participant characteristics at baseline were as follows: 53.5 ± 11.6 yrs, 53% f, BMI 32.5 ± 8.4, 42% ex-smokers, 15.1 ± 8.8 months since initial COVID-19 infection, low normal pulmonary function testing, V.O2peak 19.3 ± 5.1 mL/kg/min, 87 ± 17% predicted. After exercise training, participants significantly increased their peak work rate (+16 ± 20 W, p = 0.010) and V.O2peak (+1.55 ± 2.4 mL/kg/min, p = 0.030). Patients reported improvements in fatigue severity (-11%), depression (-42%), anxiety (-29%), and dyspnea level (-46%). There were no changes in 6MW distance or physical activity. The circulating number of CD3+, CD4+, CD19+, CD14++CD16, and CD16++CD14+ monocytes and CD56+ cells (assessed with flow cytometry) increased with acute exercise (rest to peak) and was not diminished or augmented by exercise training. Plasma concentrations of TNF-α, IL-6, IL-8, IL-10, INF-γ, and INF-λ were normal at study entry and not affected by training. Conclusions: Aerobic endurance exercise training in individuals with LC delivered beneficial effects on cardiorespiratory fitness, quality of life, anxiety, depression, and fatigue without detrimental effects on immunologic function.

Years of endurance exercise training remodel abdominal subcutaneous adipose tissue in adults with overweight or obesity.

Abnormalities in the structure and metabolic function of abdominal subcutaneous adipose tissue (aSAT) underlie many obesity-related health complications. Endurance exercise improves cardiometabolic health in adults with overweight or obesity, but the effects of endurance training on aSAT are unclear. We included male and female participants who were regular exercisers with overweight or obesity who exercised for >2 years, and cross-sectionally compared them with well-matched non-exercisers with overweight or obesity. Here we show aSAT from exercisers has a higher capillary density, lower Col6a abundance and fewer macrophages compared with non-exercisers. This is accompanied by a greater abundance of angiogenic, ribosomal, mitochondrial and lipogenic proteins. The abundance of phosphoproteins involved in protein translation, lipogenesis and direct regulation of transcripts is also greater in aSAT collected from exercisers. Exploratory ex vivo experiments demonstrate greater angiogenic capacity and higher lipid-storage capacity in samples cultured from aSAT collected from exercisers versus non-exercisers. Regular exercise may play a role in remodelling aSAT structure and proteomic profile in ways that may contribute to preserved cardiometabolic health.

Molecular Transducers of Physical Activity Consortium (MoTrPAC): human studies design and protocol.

Physical activity, including structured exercise, is associated with favorable health-related chronic disease outcomes. Although there is evidence of various molecular pathways that affect these responses, a comprehensive molecular map of these molecular responses to exercise has not been developed. The Molecular Transducers of Physical Activity Consortium (MoTrPAC) is a multicenter study designed to isolate the effects of structured exercise training on the molecular mechanisms underlying the health benefits of exercise and physical activity. MoTrPAC contains both a preclinical and human component. The details of the human studies component of MoTrPAC that include the design and methods are presented here. The human studies contain both an adult and pediatric component. In the adult component, sedentary participants are randomized to 12 wk of Control, Endurance Exercise Training, or Resistance Exercise Training with outcomes measures completed before and following the 12 wk. The adult component also includes recruitment of highly active endurance-trained or resistance-trained participants who only complete measures once. A similar design is used for the pediatric component; however, only endurance exercise is examined. Phenotyping measures include weight, body composition, vital signs, cardiorespiratory fitness, muscular strength, physical activity and diet, and other questionnaires. Participants also complete an acute rest period (adults only) or exercise session (adults, pediatrics) with collection of biospecimens (blood only for pediatrics) to allow for examination of the molecular responses. The design and methods of MoTrPAC may inform other studies. Moreover, MoTrPAC will provide a repository of data that can be used broadly across the scientific community.NEW & NOTEWORTHY The Molecular Transducers of Physical Activity Consortium (MoTrPAC) will be the first large trial to isolate the effects of structured exercise training on the molecular mechanisms underlying the health benefits of exercise and physical activity. By generating a compendium of the molecular responses to exercise, MoTrPAC will lay the foundation for a new era of biomedical research on Precision Exercise Medicine. Presented here is the design, protocols, and procedures for the MoTrPAC human studies.

10 - Eight-weeks of endurance exercise training prevents the progression of sarcopenic-obesity in aged mice

10 - Eight-weeks of endurance exercise training prevents the progression of sarcopenic-obesity in aged mice

Plasticity of the heart in response to changes in physical activity.

The human heart is very adaptable, with chamber size, wall thickness and ventricular stiffness all modified by periods of inactivity or exercise training. Herein, we summarize the cardiac adaptations induced by changes in physical activity, ranging from bed rest and spaceflight to endurance exercise training, while also highlighting how the ageing process (a long-term model of inactivity) affects cardiac plasticity. Severe inactivity during bed rest or spaceflight leads to cardiac atrophy and ventriculo-vascular stiffening. Conversely, endurance training induces eccentric hypertrophy and enhances ventricular compliance, and can be used as an effective countermeasure to prevent adverse cardiac changes during prolonged periods of bed rest or spaceflight. With sedentary ageing, the heart undergoes concentric remodelling and irreversibly stiffens at advanced age. Specifically, older adults who initiate endurance training later in life are unable to improve ventricular compliance and diastolic function, suggesting reduced cardiac plasticity with advanced age; however, lifelong exercise training prevents age-associated cardiac remodelling and maintains cardiac compliance of older adults at a level similar to those of younger healthy individuals. Nevertheless, there are still many knowledge gaps related to cardiac remodelling and changes in cardiac function induced by bed rest, exercise training and spaceflight, as well as how these different stimuli may interact with advancing age. Future studies should focus on understanding what factors (sex, age, heritability, etc.) may influence the heart's responsiveness to training or deconditioning, as well as understanding the long-term cardiac consequences of spaceflight beyond low-Earth orbit with the added stimulus of galactic cosmic radiation.

Ulk1 phosphorylation at S555 is not required for endurance training-induced improvements in exercise and metabolic capacity in mice.

Endurance exercise training improves exercise capacity as well as skeletal muscle and whole body metabolism, which are hallmarks of high quality-of-life and healthy aging. However, its mechanisms are not yet fully understood. Exercise-induced mitophagy has emerged as an important step in mitochondrial remodeling. Unc-51-like autophagy-activating kinase 1, ULK1, specifically its activation by phosphorylation at serine 555, was discovered as an autophagy driver and to be important for energetic stress-induced mitophagy in skeletal muscle, making it a potential mediator of the beneficial effects of exercise on mitochondrial remodeling. Here, we used CRISPR/Cas9-mediated gene editing and generated knock-in mice with a serine-to-alanine mutation of Ulk1 on serine 555. We now report that these mice displayed normal endurance capacity and cardiac function at baseline with a mild impairment in energy metabolism as indicated by an accelerated increase of respiratory exchange ratio (RER) during acute exercise stress; however, this was completely corrected by 8 wk of voluntary running. Ulk1-S555A mice also retained the exercise-mediated improvements in exercise capacity and metabolic flux. We conclude that Ulk1 phosphorylation at S555 is not required for exercise-mediated improvements of exercise and metabolic capacity in healthy mice.NEW & NOTEWORTHY We have used CRISPR/Cas9-mediated gene editing to generate Ulk1-S555A knock-in mice to show that loss of phosphorylation of Ulk1 at S555 blunted exercise-induced mitophagy and mildly impairs energy metabolism during exercise in healthy mice. However, the knock-in mice retained exercise training-mediated improvements of endurance capacity and energy metabolism during exercise. These findings suggest that exercise-induced mitophagy through Ulk1 activation is not required for the metabolic adaptation and improved exercise capacity in young, healthy mice.

Exercise training induces mild skeletal muscle adaptations without altering disease progression in a TDP-43 mouse model.

Exercise training is considered a nonpharmacological therapeutic approach for many diseases. Mild-to-moderate endurance exercise training is suggested to improve the mental and physical state of people with amyotrophic lateral sclerosis (ALS). The aim of the present study was to determine the capacity of symptomatic rNLS8 mice, which develop ALS-reminiscent TAR DNA-binding protein 43 (TDP-43) pathology and motor dysfunction, to perform mild-to-moderate intensity treadmill exercise training and to evaluate the effects of this training on skeletal muscle health and disease progression. Symptomatic rNLS8 mice were able to complete 4 wk of mild-to-moderate treadmill running (30 min at 6-13 m/min, 3 days a week). Exercise training induced an increase in the percentage of type IIA fibers in the tibialis anterior muscle as well as minor adaptations in molecular markers of myogenic, mitochondrial, and neuromuscular junction health in some forelimb and hindlimb muscles. However, this exercise training protocol did not attenuate the loss in motor function or delay disease progression. Alternative exercise regimens need to be investigated to better understand the role exercise training may play in alleviating symptoms of ALS.NEW & NOTEWORTHY This is the first study to investigate the capacity of symptomatic rNLS8 mice, which develop ALS-reminiscent TDP-43 pathology and motor dysfunction, to perform exercise training. We demonstrate that despite the ALS-reminiscent aggressive disease progression characterizing the rNLS8 mouse model, rNLS8 mice are capable of performing mild-to-moderate endurance treadmill training for at least 3-4 wk. We demonstrate that exercise training induces several minor skeletal muscle adaptations without delaying disease progression in rNLS8 mice.

Sprint interval training in the postpartum period maintains the enhanced cardiac output of pregnancy: A case study.

During pregnancy an increased cardiac output ( ) and blood volume (BV) occur to support fetal growth. Increased and BV also occur during chronic endurance exercise training and benefit performance. We investigated if sprint interval training (SIT) undertaken early postpartum maintains the elevated and BV of pregnancy and benefits performance. The participant, a competitive field hockey player and former cyclist, visited our laboratory at 2weeks of gestation (baseline) and postpartum pre-, mid- and post-intervention (PPpre, PPmid and PPpost). Delivery was uncomplicated and she felt ready to start the SIT programme 5weeks postpartum. Inert gas rebreathing was used to measure peak exercise ( peak); was measured with a metabolic cart; and postpartum haematological values were measured with carbon monoxide rebreathing. The 18 SIT sessions progressed from four to eight sprints at 130% of peak power output. peak increased from baseline at all postpartum time points (baseline 16.2 vs. 17.5, 16.8 and 17.2L/min at PPpre, PPmid and PPpost, respectively). Relative remained below baseline values at all postpartum measurements (baseline 44.9 vs. 41.0, 42.3 and 42.5mL/kg/min at PPpre, PPmid and PPpost, respectively) whereas absolute rapidly reached baseline values postpartum (baseline 3.19 vs. 3.12, 3.23 and 3.18L/min at PPpre, PPmid and PPpost, respectively). Postpartum BV (5257, 4271 and 5214mL at PPpre, PPmid and PPpost, respectively) and Hbmass (654, 525 and 641g at PPpre, PPmid and PPpost, respectively) were similar between PPpre and PPpost but decreased alongside peak at PPmid. Peak power was returned to pre-pregnancy values by intervention end (302 vs. 303W, baseline vs. PPpost). These findings show that SIT undertaken early postpartumdefends the elevated peak of pregnancy and rapidly returns absolute and peak power to baseline levels.

Right ventricular remodeling induced by prolonged excessive endurance exercise is mediated by upregulating Wnt/β-catenin signaling in rats

BackgroundThe aim of this study was to develop an animal model to investigate whether prolonged intensive endurance exercise induces RV remodeling, taking into account the involvement of Wnt/β-catenin signaling. MethodsFour-week-old male Wistar rats (100 to 125 g) were assigned to four groups (n = 8/group): 1) sixteen weeks of intensive (36 m/min) exercise (INT), 2) twelve weeks of the intensive exercise followed by four weeks of moderate intensity (18 m/min) exercise (INT + MOD), 3) twelve weeks of the intensive exercise followed by four weeks of detraining (INT + DT), and 4) sedentary rats (SED). The exercise protocols were performed five days a week for one h/day. Echocardiography, real-time PCR, western blotting, and histological staining were performed at the end of week sixteen. ResultsINT rats developed concentric hypertrophy without diastolic dysfunction compared to SED (p = 0.006) and INT + DT (p = 0.035). Wnt1, β-catenin and CyclinD1 proteins in the training groups were significantly higher than SED rats (p < 0.001). Interestingly, INT rats had higher protein levels than INT + DT and INT + MOD (p < 0.001), with higher gene expression compared to SED rats (p < 0.05). There was also a significant increase in collagen deposition in INT rats compared to SED (p = 0.046) and INT + DT (p = 0.034). Furthermore, INT + MOD and INT + DT rats did not show any adverse structural, functional, or histological changes. ConclusionsLong-term intensive endurance training seems to be associated with increased collagen deposition and wall thickness in the RV through Wnt/β-catenin signaling (which is concentration dependent), without changes in diastolic function. Clinical perspectiveOver the past decades, there has been an ongoing debate about whether the structural and functional adaptations of the cardiovascular system in trained endurance athletes are benign physiological responses to training or potentially pathological changes related to disease. While the adaptations of the left heart are well-documented, the remodeling of the right heart remains a subject of discussion. To gain insights into the ability of sustained high-intensity exercise to cause adverse right ventricular (RV) remodeling, we conducted an experimental study in which male rats were trained to run vigorously for 1 h daily over a 16-week period and compared them to a parallel group of sedentary control rats. Our findings revealed that intense long-term exercise induced morphological changes along with fibrosis affecting the RV. These fibrotic changes were a result of the 16-week vigorous exercise training regimen. If these results are confirmed in humans, they suggest that prolonged high-intensity endurance exercise training may lead to adverse cardiac remodeling. Our findings have important potential implications for the assessment of cardiac remodeling in individuals engaged in high-level exercise training.

Skeletal muscle BMAL1 is necessary for transcriptional adaptation of local and peripheral tissues in response to endurance exercise training

ObjectiveIn this investigation, we addressed the contribution of the core circadian clock factor, BMAL1, in skeletal muscle to both acute transcriptional responses to exercise and transcriptional remodeling in response to exercise training. Additionally, we adopted a systems biology approach to investigate how loss of skeletal muscle BMAL1 altered peripheral tissue homeostasis as well as exercise training adaptations in iWAT, liver, heart, and lung of male mice. MethodsCombining inducible skeletal muscle specific BMAL1 knockout mice, physiological testing and standardized exercise protocols, we performed a multi-omic analysis (transcriptomics, chromatin accessibility and metabolomics) to explore loss of muscle BMAL1 on muscle and peripheral tissue responses to exercise. ResultsMuscle-specific BMAL1 knockout mice demonstrated a blunted transcriptional response to acute exercise, characterized by the lack of upregulation of well-established exercise responsive transcription factors including Nr4a3 and Ppargc1a. Six weeks of exercise training in muscle-specific BMAL1 knockout mice induced significantly greater and divergent transcriptomic and metabolomic changes in muscle. Surprisingly, liver, lung, inguinal white adipose and heart showed divergent exercise training transcriptomes with less than 5% of ‘exercise-training’ responsive genes shared for each tissue between genotypes. ConclusionsOur investigation has uncovered the critical role that BMAL1 plays in skeletal muscle as a key regulator of gene expression programs for both acute exercise and training adaptations. In addition, our work has uncovered the significant impact that altered exercise response in muscle and its likely impact on the system plays in the peripheral tissue adaptations to exercise training. Our work also demonstrates that if the muscle adaptations diverge to a more maladaptive state this is linked to increased gene expression signatures of inflammation across many tissues. Understanding the molecular targets and pathways contributing to health vs. maladaptive exercise adaptations will be critical for the next stage of therapeutic design for exercise mimetics.

Comparison of The Effectiveness of Aerobic Endurance Training and Resistance Exercise on Reducing Daily Blood Sugar in The Elderly at The Puter Community Health Center Bandung City

Diabetes Mellitus (DM) is a chronic condition that occurs when there is an increase in glucose levels in the blood because the body cannot produce insulin or use insulin effectively. Insulin is an important hormone produced in the body's pancreatic gland, which transports glucose from the bloodstream into the body's cells where the glucose is converted into energy. This study uses a comparative study with experimental method to find out the comparison results of the treatment given to samples from aerobic exercise intervention treatment with resistance exercise, The first group will do Aerobic Endurance Exercise by walking for 20 minutes. While the second group will do Resistance Exercise by doing strength training or resistance training for 20 minutes, rest time is 15 seconds and the movement is done as many as 2 sets and 10 repetitions. Subject characteristics based on average age (61.58 ± 6.50), body weight (71.86 ± 9.76), body height (157.27 ± 8.99), and BMI of elderly people suffering from diabetes mellitus falls into the obese category with a value of (27.71 ± 4.23). The value of aerobic before exercise is (26.41 ± 33.67) after exercise it decrease (11.74 ± 10.28), resistance exercise before exercise is (31.74 ± 54.10) after exercise it decrease (9.33 ± 23.46). In this study it can be concluded that aerobic endurance and resistance exercise can reduce the increase in blood sugar in the elderly, but when compared to the two exercises, resistance exercise suppresses the increase in blood sugar more, of course with the appropriate intensity.

The influence of endurance exercise training on myocardial fibrosis and arrhythmogenesis in a coxsackievirus B3 myocarditis mouse model

Nonischaemic myocardial fibrosis is associated with cardiac dysfunction, malignant arrhythmias and sudden cardiac death. In the absence of a specific aetiology, its finding as late gadolinium enhancement (LGE) on cardiac magnetic resonance imaging is often attributed to preceding viral myocarditis. Athletes presenting with ventricular arrhythmias often have nonischaemic LGE. Previous studies have demonstrated an adverse effect of exercise on the course of acute viral myocarditis. In this study, we have investigated, for the first time, the impact of endurance training on longer-term outcomes such as myocardial fibrosis and arrhythmogenicity in a murine coxsackievirus B3 (CVB)-induced myocarditis model. Male C57BL/6J mice (n = 72) were randomly assigned to 8 weeks of forced treadmill running (EEX) or no exercise (SED). Myocarditis was induced 2 weeks later by a single intraperitoneal injection with CVB, versus vehicle in the controls (PBS). In a separate study, mice (n = 30) were subjected to pretraining for 13 weeks (preEEX), without continuation of exercise during myocarditis. Overall, continuation of exercise resulted in a milder clinical course of viral disease, with less weight loss and better preserved running capacity. CVB-EEX and preEEX-CVB mice tended to have a lower mortality rate. At sacrifice (i.e. 6 weeks after inoculation), the majority of virus was cleared from the heart. Histological assessment demonstrated prominent myocardial inflammatory infiltration and cardiomyocyte loss in both CVB groups. Inflammatory lesions in the CVB-EEX group contained higher numbers of pro-inflammatory cells (iNOS-reactive macrophages and CD8+ T lymphocytes) compared to these in CVB-SED. Treadmill running during myocarditis increased interstitial fibrosis [82.4% (CVB-EEX) vs. 56.3% (CVB-SED); P = 0.049]. Additionally, perivascular and/or interstitial fibrosis with extensive distribution was more likely to occur with exercise [64.7% and 64.7% (CVB-EEX) vs. 50% and 31.3% (CVB-SED); P = 0.048]. There was a numerical, but not significant, increase in the number of scars per cross-section (1.9 vs. 1.2; P = 0.195), with similar scar distribution and histological appearance in CVB-EEX and CVB-SED. In vivo electrophysiology studies did not induce sustained monomorphic ventricular tachycardia, only nonsustained (usually polymorphic) runs. Their cumulative beat count and duration paralleled the increased fibrosis between CVB-EEX and CVB-SED, but the difference was not significant (P = 0.084 for each). Interestingly, in mice that were subjected to pretraining only without continuation of exercise during myocarditis, no differences between pretrained and sedentary mice were observed at sacrifice (i.e. 6 weeks after inoculation and training cessation) with regard to myocardial inflammation, fibrosis, and ventricular arrhythmogenicity. In conclusion, endurance exercise during viral myocarditis modulates the inflammatory process with more pro-inflammatory cells and enhances perivascular and interstitial fibrosis development. The impact on ventricular arrhythmogenesis requires further exploration.