Moderate-intensity Exercise Training Research Articles

Exercise Training in Patients With Hypertrophic Cardiomyopathy Without Left Ventricular Outflow Tract Obstruction: A Randomized Clinical Trial.

Patients with hypertrophic cardiomyopathy without left ventricular outflow tract obstruction commonly experience reduced exercise capacity. Physical training improves exercise capacity in these patients, but whether the underlying effects of exercise are a result of central hemodynamic or peripheral improvement is unclear. This study assessed whether exercise training reduces left ventricular filling pressure measured during exercise in patients with hypertrophic cardiomyopathy without left ventricular outflow tract obstruction. Between March 2019 and June 2022, patients with hypertrophic cardiomyopathy without left ventricular outflow tract obstruction were randomly assigned (1:1) to a 12-week (3 h/wk) supervised, moderate-intensity exercise training program or continued usual activity. The primary outcome was the change in invasively measured pulmonary capillary wedge pressure during mild exercise (25 W) from baseline to week 12. Pressure tracings were analyzed offline by a blinded investigator. Secondary outcomes included changes in peak oxygen consumption, cardiac index, quality of life, echocardiographic indices of diastolic function, and natriuretic peptides. Of 59 patients randomized (mean age, 58.1±12.2 years; 27% women), 51 (86%) completed all follow-up assessments. At week 12, the change in 25-W pulmonary capillary wedge pressure was -2.8±6.8 mm Hg in the exercise group, compared with +1.2±4.9 mm Hg in the usual-activity group (between-group difference, 4.0 mm Hg [95% CI, 0.7-7.3]; P=0.018). Peak oxygen consumption improved by +1.8±2.0 mL/kg/min in the exercise group versus -0.3±3.1 mL/kg/min in the usual-activity group (P=0.005). Exercise training improved the ventilatory efficiency (VE/VCO2) slope compared with usual activity (between-group difference, 2.0 [95% CI, 0.6-3.5]; P=0.006). Peak cardiac index improved by +0.38±1.38 L/min/m2 in exercise versus -0.85±1.20 L/min/m2 in the usual-activity group (P=0.002). Change in overall Kansas City Cardiomyopathy Questionnaire score was similar between groups. However, the change in physical limitation scores (+8.4±12.0 points in exercise versus +0.7±6.8 points in usual-activity group; P=0.034) and quality-of-life scores (+8.7±18.0 points in exercise versus 0.7±4.0 points in usual-activity group; P=0.01) differed significantly. There were no significant changes in diastolic function assessed by echocardiography or in natriuretic peptides. In patients with hypertrophic cardiomyopathy without left ventricular outflow tract obstruction, a 12-week moderate-intensity exercise training program resulted in reduced left ventricular filling pressures at mild exertion and improved exercise performance. URL: https://www.clinicaltrials.gov; Unique identifier: NCT03537183.

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.

Moderate intensity exercise training ameliorates the heart failure with preserved ejection fraction phenotype in a preclinical model by improving cardiometabolic fitness

Abstract Introduction and Aim Exercise intolerance is a hallmark feature of patients with heart failure with preserved ejection fraction (HFpEF).While clinical evidence suggests potential benefits of exercise training in HFpEF, its mechanisms remain largely unknown.In this study, we used a translationally relevant murine model of cardiometabolic HFpEF(1) to assess whether moderate intensity continuous training(MICT) can ameliorate the HFpEF phenotype in mice and promote cardiometabolic health. Methods Twenty-five adult, male C57BL/6N were fed with the combination of high fat diet(HFD;D12492,Research diet)and L-NAME(0.5 g/L,in drinking water) for 15 weeks to elicit HFpEF as previously described(1).After the establishment of the HFpEF phenotype, mice were randomized in two groups:sedentary(SED,n= 10) and exercised(MICT,n=15)mice.MICT was carried out according to the protocol:running on 10-degree positive inclination treadmill for 8 consecutive weeks,5 times/week,60 minutes/day,at a speed gradually increasing from 0.1 to 0.2 m/sec on a weekly basis.Morphometry, echocardiography(TTE),isoproterenol-induced stress echocardiography(SE),time domain nuclear magnetic resonance, and treadmill exhaustion tests were performed at the beginning and end of MICT.Additionally, at the end of MICT blood and tissues were collected for proteomics analysis(Fig1).Non-trained male C57BL/6N mice(37w) were used as controls for the HFpEF mice. Results Before randomization, all HFpEF mice were similar in terms of phenotypic characteristics. Compared to SED mice, MICT induced a significantly decrease in body weight driven by a reduction of total fat mass with an increased in lean mass(Fig2A+B).Interestingly, MICT had no impact on skeletal muscle mass for all different muscle groups evaluated (extensor digitorum longus, soleus and tibialis anterior).Importantly, MICT led to a significant improvement in exercise capacity in HFpEF mice, as shown by increased running distance and time, surpassing even the running distance seen in non-HFpEF mice (SED:62.8±18.7,MICT:305.7±13.9,non-HFpEF mice: 129.72±15.2meters,p<0.001).Preclinical surrogate of HFpEF such as pulmonary congestion, evaluated by index lung weights, improved after aerobic training.Following MICT there was a marked improvement in diastolic dysfunction(measured by E/E’ratio) both at rest(SED:36.5±3.3,MICT:23.3±5.09,p<0.001) and after isoproterenol challenge(SED:42.6±15.1,MICT:26.09±3.75,p<0.001)(Fig2C).Moreover, the wet cardiac mass was lower in the MICT group(Fig2A), suggesting potential amelioration in cardiac hypertrophy following aerobic training. Conclusion Eight weeks of supervised MICT on treadmill improves functional status, exercise capacity, and diastolic function in a cardiometabolic HFpEF murine model.The most significant effects were seen on weight loss and fat mass reduction.Our findings suggest a beneficial impact of aerobic exercise in mitigating HFpEF by improving metabolic fitness in the preclinical HFpEF model.Fig1-Study DesignFig2-Characteristics SED vs MICT groups

Financial analysis of a locomotor exercise trial for post-stroke recovery: insights from the HIT Stroke Trial

BackgroundNavigating the complexities of post-stroke recovery trials requires addressing challenges in participant recruitment and retention and effective resource management to ensure trial success. The aim of this study was to examine the financial requirements associated with conducting the Moderate-Intensity Exercise vs. High-Intensity Interval Training to Recover Walking Post-Stroke (HIT Stroke Trial) at a single site encompassing a wide catchment area, recognizing the intricate challenges of participant recruitment and retention inherent in post-stroke recovery trials.MethodsTo determine cost, study expense reports were gathered and divided into seven categories: recruitment, screening assessments, baseline assessments, intervention, outcome assessments, retention, and oversight. Categories were then further divided into chronological order for initial contact and prescreening, consenting, initial screening, and baseline testing. The 12-week intervention was divided into 4-week blocks: intervention block 1, post 4-week outcome testing, intervention block 2, post 8-week outcome testing, intervention block 3, and post 12-week outcome testing.ResultsTotal direct cost for site execution was $539,768 with cost per participant approximated as $35,984. Oversight costs accounted for 65.8% of the budget at $355,661. To achieve goals related to inclusive participant recruitment ($21,923) and retention ($28,009), our site costs totaled $49,932. Direct study-related costs included screening assessments ($5,905), baseline assessments ($15,028), intervention ($76,952), and outcome assessments ($36,288).DiscussionClinical trials focusing on walking rehabilitation and exercise, particularly those requiring multiple assessment visits, demand rigorous oversight. This cost analysis provides important and critical insight into the expenses required to successfully execute an exercise-based walking rehabilitation trial in the United States.

Effects of Lower Limb Heat Therapy, Exercise Training, or a Combined Intervention on Vascular Function: A Randomized Controlled Trial.

To compare the effects of 8 weeks of no intervention (CON), lower limb heat therapy (HEAT), moderate-intensity exercise training (EX), or combined training and therapy (HEATEX) in young, healthy recreationally active adults. Sixty participants (23 ± 3 years, 30 females) were randomly allocated into either CON (n = 15), HEAT (n = 15), EX (n = 14), or HEATEX (n = 16). The primary outcome was vascular function, assessed through brachial artery flow-mediated dilation tests (BA FMD). Secondary measures included arterial stiffness (pulse wave velocity, PWV); cardiorespiratory fitness (VO2peak); body composition; and quadriceps muscle strength. There were no differences in BA FMD between the groups before and after the interventions (all p > 0.05). Both interventions with a heating component were associated with within-group reductions in carotid-femoral PWV, and increases in absolute and relative VO2peak after 8 weeks (HEAT: ∆-0.27 [-0.53, -0.02] m/s, ∆0.18 [0.06, 0.29] L/min, ∆2.18 [0.60, 3.76] ml/kg/min, respectively; HEATEX: ∆-0.33 [-0.58, -0.09], ∆0.21 [0.11, 0.32] L/min, ∆2.59 [1.06, 4.12] ml/kg/min, respectively), but no between-group differences were observed (p = 0.25, p = 0.21, and p = 0.55, respectively). There was also a within-group decrease in body fat percentage with EX (∆-1.37 [-2.45, -0.29] %), but no changes in leg strength in any of the groups (p = 0.79). This randomized controlled trial is the first to examine the efficacy of lower limb heating against traditionally prescribed exercise training. In our young cohort, 8 weeks of training and/or therapy was insufficient to improve vascular function. More intense protocols and longer interventions involving lower limb heating may be required to elicit improvements in health outcomes.

Impact of low-to moderate-intensity exercise training on the mRNA expression of purine receptors across various vessels in SHR.

In this study, we developed an exercise training protocol for assessing both blood pressure dynamics and mRNA expression levels of purine receptors in various vascular tissues during physical activity. The objective is to assess the impact of exercise training on blood pressure regulation in spontaneously hypertensive rats (SHR) and purine receptors in vascular tissues. Wistar Kyoto (WKY) and SHR rats were randomly allocated into sedentary (Sed) and exercise training (ExT) groups. Rats in the Sed groups were allowed unrestricted movement, whereas those in the ExT groups underwent a 16-week regimen of low- to moderate-intensity treadmill exercise. Throughout the intervention period, blood pressure measurements and body weight recordings were conducted. Additionally, mRNA expressions of purine receptors P2X1, P2Y1, and P2Y2 in renal artery (RA), internal carotid artery (Int), thoracic aorta (Aor), and caudal artery (Cau) tissues were assessed. In the Sed group, body weight of SHR rats was observed to be lower compared to the three other groups. Over the course of the exercise regimen, blood pressure in the ExT group of SHR rats reduced gradually, converging towards levels similar to those observed in WKY rats by the conclusion of the exercise period. Regarding mRNA expression patterns of P2X1 receptors across the four blood vessels, WKY and SHR rats demonstrated similar sequences, consistently displaying the highest expression levels in the Cau. Conversely, mRNA expressions of P2Y1 and P2Y2 receptors exhibited distinct sequences across the four blood vessels in both WKY and SHR rats. Notably, compared to the Sed group of WKY rats, mRNA expression of P2X1 receptor in the Int of SHR rats revealed an increase, while expressions in the Aor of WKY rats and the Cau of SHR rats decreased following exercise. Expression of P2Y1 receptor mRNA decreased across all four types of blood vessels in SHR rats. Post-exercise, P2Y1 receptor mRNA expression increased in the Aor, decreased in the Cau of WKY rats, and increased in the Int and renal artery (RA) of SHR rats. Conversely, expressions of P2Y2 receptor mRNA decreased in the Int and Aor of SHR rats. Except for the Aor of WKY rats, expressions of P2Y2 receptor mRNA increased in the other arteries of both rat types following exercise. Differences in the distribution of purine receptor subtypes among distinct arterial segments in both WKY and SHR rats were observed. Exercise training was found to enhance mRNA expression levels of P2Y receptors in these rat models. This finding implies that exercise training might reduce hypertension in SHR rats by bolstering the purinergic relaxation response.

10-20-30 exercise training improves fitness and health.

Intense interval exercise training has been shown to improve performance and health of untrained and trained people. However, due to the exercise intensity causing high-perceived exertion, the participants often do not wish to continue the training. The 10-20-30 training concept consists of low intensity for 30s, 20s at a moderate pace, and then 10s with high intensity either running or cycling. A 10-20-30 training session consist of two to four 5-min blocks. The 10-20-30 training improved fitness and performance as well as lowered blood pressure and body fat of both untrained and trained individuals even with a significant reduction in the training volume. Similarly, hypertensive, diabetic, and asthmatic patients lowered body fat, improved fitness, and performance during a 10-20-30-training intervention period. In addition, hypertensive patients reduced systolic and diastolic blood pressure markedly with the 10-20-30 training twice a week for 8weeks. Diabetic patients lowered long-term blood sugar (HbA1c), which did not occur with moderate-intensity exercise training. Furthermore, asthmatic patients improved their control of asthma and asthma-related quality of life with the 10-20-30 training. The adherence for the patient groups was high (>80%), and no adverse events were reported. Thus, the 10-20-30 training seems to be time efficient and feasible for untrained and trained individuals as well as patients and may be used in the prevention and treatment of noncommunicable diseases.

Greater hepatic lipid saturation is associated with impaired glycaemic regulation in men with metabolic dysfunction-associated steatotic liver disease but is not altered by 6 weeks of exercise training.

To examine the impact of impaired glycaemic regulation (IGR) and exercise training on hepatic lipid composition in men with metabolic dysfunction-associated steatotic liver disease (MASLD). In Part A (cross-sectional design), 40 men with MASLD (liver proton density fat fraction [PDFF] ≥5.56%) were recruited to one of two groups: (1) normal glycaemic regulation (NGR) group (glycated haemoglobin [HbA1c] < 42 mmol∙mol-1 [<6.0%]; n = 14) or (2) IGR group (HbA1c ≥ 42 mmol∙mol-1 [≥6.0%]; n = 26). In Part B (randomized controlled trial design), participants in the IGR group were randomized to one of two 6-week interventions: (1) exercise training (EX; 70%-75% maximum heart rate; four sessions/week; n = 13) or (2) non-exercise control (CON; n = 13). Saturated (SI; primary outcome), unsaturated (UI) and polyunsaturated (PUI) hepatic lipid indices were determined using proton magnetic resonance spectroscopy. Additional secondary outcomes included liver PDFF, HbA1c, fasting plasma glucose (FPG), homeostatic model assessment of insulin resistance (HOMA-IR), peak oxygen uptake (VO2 peak), and plasma cytokeratin-18 (CK18) M65, among others. In Part A, hepatic SI was higher and hepatic UI was lower in the IGR versus the NGR group (p = 0.038), and this hepatic lipid profile was associated with higher HbA1c levels, FPG levels, HOMA-IR and plasma CK18 M65 levels (rs ≥0.320). In Part B, hepatic lipid composition and liver PDFF were unchanged after EX versus CON (p ≥ 0.257), while FPG was reduced and VO2 peak was increased (p ≤ 0.030). ΔVO2 peak was inversely associated with Δhepatic SI (r = -0.433) and positively associated with Δhepatic UI and Δhepatic PUI (r ≥ 0.433). Impaired glycaemic regulation in MASLD is characterized by greater hepatic lipid saturation; however, this composition is not altered by 6 weeks of moderate-intensity exercise training.

Effects of Moderate- Versus Vigorous-Intensity Exercise Training on Asthma Outcomes in Adults

The therapeutic effects of exercise have prompted calls for it to be embedded into standard asthma care, but evidence informing the optimal exercise intensity is lacking. This study aimed to compare the effects of moderate- and vigorous-intensity aerobic exercise training on asthma outcomes and inflammation. This was a 12-week randomized controlled trial in 46 adults with asthma randomized to either (1) 45-minute moderate-intensity exercise training 3 times/wk, (2) 30-minute vigorous-intensity exercise training 3 times/wk, or (3) the control group. Asthma-related quality of life (AQLQ), asthma control (ACQ), cardiorespiratory fitness, body composition, and airway and systemic inflammation were assessed before and after the intervention. Forty-one participants completed the study (89% retention). The moderate-intensity group had a statistically and clinically significant improvement in AQLQ (0.63 [0.33-0.93], P < .001) and ACQ (-0.51 [-0.83 to -0.19], P= .003) relative to control. The vigorous-intensity group had a statistically, but not clinically, significant improvement in AQLQ (0.46 [0.14-0.80], P= .007) and ACQ (-0.36 [-0.69 to -0.02], P= .040) relative to control. After moderate-intensity training, there was a reduction in sputum macrophage (-1341 [-2491 to -191]× 104/mL, P= .024) and lymphocyte (-114 [-220 to -8]× 104/mL, P= .036) counts relative to control. A reduction in android fat mass, but not a change in fitness, was associated with improved AQLQ (rs= -0.341, P= .030) and reduced sputum IL-6 (rs= 0.422, P= .013). Our findings suggest that both moderate-intensity and vigorous-intensity aerobic exercise training are associated with improvements in clinical asthma outcomes and, therefore, both intensities could be recommended as an adjuvant asthma therapy.

Moderate-intensity aerobic exercise training improves CD8+ tumor-infiltrating lymphocytes effector function by reducing mitochondrial loss

Aerobic exercise training (AET) has emerged as a strategy to reduce cancer mortality, however, the mechanisms explaining AET on tumor development remain unclear. Tumors escape immune detection by generating immunosuppressive microenvironments and impaired Tcell function, which is associated with Tcell mitochondrial loss. AET improves mitochondrial content and function, thus we tested whether AET would modulate mitochondrial metabolism in tumor-infiltrating lymphocytes (TIL). Balb/c mice were subjected to a treadmill AET protocol prior to CT26 colon carcinoma cells injection and until tumor harvest. Tissue hypoxia, TIL infiltration and effector function, and mitochondrial content, morphology and function were evaluated. AET reduced tumor growth, improved survival, and decreased tumor hypoxia. An increased CD8+ TIL infiltration, IFN-γ and ATP production promoted by AET was correlated with reduced mitochondrial loss in these cells. Collectively, AET decreases tumor growth partially by increasing CD8+ TIL effector function through an improvement in their mitochondrial content and function.

Aerobic exercise training engages the canonical wnt pathway to improve pulmonary function and inflammation in COPD

BackgroundWe studied whether the exercise improves cigarette smoke (CS) induced chronic obstructive pulmonary disease (COPD) in mice through inhibition of inflammation mediated by Wnt/β-catenin-peroxisome proliferator-activated receptor (PPAR) γ signaling.MethodsFirstly, we observed the effect of exercise on pulmonary inflammation, lung function, and Wnt/β-catenin-PPARγ. A total of 30 male C57BL/6J mice were divided into the control group (CG), smoke group (SG), low-intensity exercise group (LEG), moderate-intensity exercise group (MEG), and high-intensity exercise group (HEG). All the groups, except for CG, underwent whole-body progressive exposure to CS for 25 weeks. Then, we assessed the maximal exercise capacity of mice from the LEG, MEG, and HEG, and performed an 8-week treadmill exercise intervention. Then, we used LiCl (Wnt/β-catenin agonist) and XAV939 (Wnt/β-catenin antagonist) to investigate whether Wnt/β-catenin-PPARγ pathway played a role in the improvement of COPD via exercise. Male C57BL/6J mice were randomly divided into six groups (n = 6 per group): CG, SG, LiCl group, LiCl and exercise group, XAV939 group, and XAV939 and exercise group. Mice except those in the CG were exposed to CS, and those in the exercise groups were subjected to moderate-intensity exercise training. All the mice were subjected to lung function test, lung histological assessment, and analysis of inflammatory markers in the bronchoalveolar lavage fluid, as well as detection of Wnt1, β-catenin and PPARγ proteins in the lung tissue.ResultsExercise of various intensities alleviated lung structural changes, pulmonary function and inflammation in COPD, with moderate-intensity exercise exhibiting significant and comprehensive effects on the alleviation of pulmonary inflammation and improvement of lung function. Low-, moderate-, and high-intensity exercise decreased β-catenin levels and increased those of PPARγ significantly, and only moderate-intensity exercise reduced the level of Wnt1 protein. Moderate-intensity exercise relieved the inflammation aggravated by Wnt agonist. Wnt antagonist combined with moderate-intensity exercise increased the levels of PPARγ, which may explain the highest improvement of pulmonary function observed in this group.ConclusionsExercise effectively decreases COPD pulmonary inflammation and improves pulmonary function. The beneficial role of exercise may be exerted through Wnt/β-catenin-PPARγ pathway.

Effects of short-term moderate intensity exercise on the serum metabolome in older adults: a pilot randomized controlled trial

BackgroundWe previously reported changes in the serum metabolome associated with impaired myocardial relaxation in an asymptomatic older community cohort. In this prospective parallel-group randomized control pilot trial, we subjected community adults without cardiovascular disease to exercise intervention and evaluated the effects on serum metabolomics.MethodsBetween February 2019 to November 2019, thirty (83% females) middle-aged adults (53 ± 4 years) were randomized with sex stratification to either twelve weeks of moderate-intensity exercise training (Intervention) (n = 15) or Control (n = 15). The Intervention group underwent once-weekly aerobic and strength training sessions for 60 min each in a dedicated cardiac exercise laboratory for twelve weeks (ClinicalTrials.gov: NCT03617653). Serial measurements were taken pre- and post-intervention, including serum sampling for metabolomic analyses.ResultsTwenty-nine adults completed the study (Intervention n = 14; Control n = 15). Long-chain acylcarnitine C20:2-OH/C18:2-DC was reduced in the Intervention group by a magnitude of 0.714 but increased in the Control group by a magnitude of 1.742 (mean difference −1.028 age-adjusted p = 0.004). Among Controls, alanine correlated with left ventricular mass index (r = 0.529, age-adjusted p = 0.018) while aspartate correlated with Lateral e’ (r = −764, age-adjusted p = 0.016). C20:3 correlated with E/e’ ratio fold-change in the Intervention group (r = −0.653, age-adjusted p = 0.004). Among Controls, C20:2/C18:2 (r = 0.795, age-adjusted p = 0.005) and C20:2-OH/C18:2-DC fold-change (r = 0.742, age-adjusted p = 0.030) correlated with change in E/A ratio.ConclusionsCorresponding relationships between serum metabolites and cardiac function in response to exercise intervention provided pilot observations. Future investigations into cellular fuel oxidation or central carbon metabolism pathways that jointly impact the heart and related metabolic systems may be critical in preventive trials.

Aerobic training reduces microglial activation and TNFα release in the hypothalamus of hypertensive rats

Spontaneously hypertensive rats (SHR) exhibit autonomic imbalance and blood-brain barrier (BBB) dysfunction, a pathophysiological condition that can be corrected by exercise training. Although microglia cells are not part of the structure of the BBB itself, they modulate it function through the synthesis and release of cytokines. In hypertension condition, for instance, microglia are activated releasing pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNFα), which is able to break down different BBB constituents. Therefore, here we hypothesized that the benefit of exercise training to ameliorate BBB integrity of hypertensive rats could be due to the reduction in the release of TNFα by microglia at the hypothalamus level. Thus, our aim is to evaluate whether microglial activation, and consequent TNFα release, in the hypothalamus of SHR can be affected by aerobic exercise training. Wistar and SHR male rats (CEUA ICB/USP #3407080618) aged 90 days were divided into four groups: sedentary (W-S n=6) and trained Wistar (W-T n=6), sedentary (SHR-S n=6) and trained SHR (SHR-T n=6). Exercise trained animals were submitted to moderate intensity of aerobic training on a treadmill (50%-60% of maximum capacity, 1 h/day, 5 days/week, for 4 weeks). At the end of the 4th week of training, the hypothalamus, brainstem, and cortex of all groups were collected and processed for isolation of mononuclear cells, followed by flow cytometry analysis to evaluate the microglial labeling by CD45lowCD11b+, gated for TNFα+. All data as analyzed by two-way ANOVA followed by Bonferroni’s post-test. Trained animals showed performance gains compared to their control groups (Velocity: W-S: 1.07±0.23km/h vs. W-T: 1.7±0.36km/h, p&lt;0.0001 and SHR-S: 1.25±0.17km/h vs. SHT-T: 1.95±0.16km/h, p&lt;0.0001; Distance: W-S: 85±42m vs. W-T: 218±95m, p=0.0042 and SHR-S: 124±44m vs. SHT-T: 315±21m, p&lt;0.001). Hypertensive animals present an elevated neuroinflammation degree compared to normotensive subjects, by increased microglia activation (W-S: 0.65±0.39% vs. SHR-S: 7.0±1.4%, p&lt;0.0001) and TNFα release (W-S: 33.9±24.6% vs. SHR-S: 95.2±3.6%, p=0.0007). After training, hypertensive rats exhibited a reduction in hypothalamic microglial activation in a similar way to sedentary and trained Wistar (CD45lowCD11b+, SHR-T: 0.55±0.26%: vs. W-S:0.65±0.39% p=0.99; vs. W-T: 0.41±0.28% p=0.98; vs. SHR-S: 7.0±1.4% p&lt;0.0001). TNFα release also reduced in hypothalamus of SHR-T (CD11b+TNFα+, SHR-T: 59.4±17.0%: vs. W-S: 33.9±24.6% p=0.15; vs. W-T: 41.9±4.6% p=0.6; vs. SHR-S: 95.2±3.6% p&lt;0.01). SHR-S exhibit higher microglial activation and TNFα release in brainstem compared to W-S, but 4 weeks of training was not enough to reduce this condition. No difference was observed in cortex. In conclusion, exercise training of moderate intensity is effcient to reduce microglia activation and consequently TNFα release in the hypothalamus of hypertensive animals, which could be one of the causes affecting the integrity of the BBB in hypertensive animals. FAPESP #2018/14544-6; #2022/07465-8. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Comparing high-intensity versus moderate-intensity exercise training in coronary artery disease patients: a randomized controlled trial with 6- and 12-month follow-up

Abstract Aim This study aimed to investigate the long-term effects of two exercise-based CR programs on physical activity (PA), sedentary behavior, physical fitness, quality of life (QoL), and mental health in coronary artery disease (CAD) patients. Subject and methods Seventy-two CAD participants were randomized (1:1:1) into HIIT, MICT, and control groups. Both training programs spanned 6 weeks with three supervised treadmill exercise sessions per week. MICT targeted ≈70–75% of peak heart rate (HR), while HIIT aimed for ≈85–95% of peak HR. The control group adhered to standard medical recommendations. Assessments at 6- and 12-months post-intervention included body composition, aerobic capacity, muscle strength, PA, SB, QoL, anxiety, and depression. Results Over the 6- and 12-month follow-up periods, both exercise groups maintained the levels of aerobic capacity (HIIT ≈ 19.6 ml kg−1 min−1, MICT ≈ 17.8 ml kg−1 min−1), QoL, and PA compared to baseline (p &lt; .001). Symptoms of anxiety and depression remained lower than baseline (p &lt; .001). The HIIT group demonstrated a significant decreasing trend in waist circumference (∆m3−m2% −2 cm, p = .033) compared to MICT (p = .016) and control (p = .001) at 6 months of follow-up. It was maintained at 12 months of follow-up with significant differences to MICT (p = .018) and control (p = .001). In contrast, the control group experienced deteriorations in body composition, SB, symptoms of anxiety, and depression, along with a decline in aerobic capacity over time. Conclusion Encouraging CAD patients to maintain elevated PA levels can promote cardiovascular, WC, and mental health. CR exercise programs can reduce cardiovascular risk factors and induce favorable lifestyle changes. Notably, HIIT demonstrated sustained improvements surpassing those of MICT. These findings underscore the importance of structured exercise-based CR programs in optimizing long-term outcomes for CAD patients. Trial Registration https://clinicaltrials.gov/ct2/show/NCT03538119 on May 25, 2018.

Moderate-Intensity and High-Intensity Interval Exercise Training Offer Equal Cardioprotection, with Different Mechanisms, during the Development of Type 2 Diabetes in Rats.

Endurance exercise training is a promising cardioprotective strategy in type 2 diabetes mellitus (T2DM), but the impact of its intensity is not clear. We aimed to investigate whether and how isocaloric moderate-intensity exercise training (MIT) and high-intensity interval exercise training (HIIT) could prevent the adverse cardiac remodeling and dysfunction that develop T2DM in rats. Male rats received a Western diet (WD) to induce T2DM and underwent a sedentary lifestyle (n = 7), MIT (n = 7) or HIIT (n = 8). Insulin resistance was defined as the HOMA-IR value. Cardiac function was assessed with left ventricular (LV) echocardiography and invasive hemodynamics. A qPCR and histology of LV tissue unraveled underlying mechanisms. We found that MIT and HIIT halted T2DM development compared to in sedentary WD rats (p < 0.05). Both interventions prevented increases in LV end-systolic pressure, wall thickness and interstitial collagen content (p < 0.05). In LV tissue, HIIT tended to upregulate the gene expression of an ROS-generating enzyme (NOX4), while both modalities increased proinflammatory macrophage markers and cytokines (CD86, TNF-α, IL-1β; p < 0.05). HIIT promoted antioxidant and dicarbonyl defense systems (SOD2, glyoxalase 1; p < 0.05) whereas MIT elevated anti-inflammatory macrophage marker expression (CD206, CD163; p < 0.01). We conclude that both MIT and HIIT limit WD-induced T2DM with diastolic dysfunction and pathological LV hypertrophy, possibly using different adaptive mechanisms.

Exercise alters molecular rhythms in the central nervous system that negatively correlate with depression-like behavior.

Major depressive disorder (MDD) ranks among the top 10 leading causes of death. However, exercise is known to improve depressive symptoms but the mechanism responsible is still unknown. To date, numerous studies have shown that molecular rhythms and exercise are associated with MDD. Thus, we hypothesized that exercise could affect the expression of central nervous system clock genes to improve depressive symptoms. Ninety adult male Sprague-Dawley rats (250 g) were divided into a control Normal Group, an unpredictable chronic mild stress (CMS) treated CMS Group and an Exercise Group, which was intervened by a moderate-intensity exercise training on a treadmill at 2 p.m. every day for 4 weeks after CMS treatment. The open field test, elevated plus maze and forced swim test were employed to test mood-related behaviors. The telemetry recording method recorded voluntary locomotor activity and core body temperature. Expression of core clock genes in the suprachiasmatic nucleus (SCN) was tested by qRT-PCR. Compared with the CMS Group, depressive symptoms were improved in the Exercise Group ( P < 0.05). Moreover, the periodic changes of molecular rhythms in the Exercise Group were close to those of rats in Normal Group. Next, exercise increased oscillations of expression of core clock genes in SCN after CMS treatment, and the amplitudes of core clock gene expression oscillations were negatively correlated with depressive-like behavior. Our findings suggested that exercise could change the expressions of central clock genes in MDD animals, and this effect was positively correlated with the improvement of depressive symptoms by exercise.

Interaction of oat bran and exercise training improved exercise adaptability via alleviating oxidative stress and promoting energy homeostasis.

Skeletal muscle performance is influenced by both diet and the mode of exercise, with diet playing a crucial role in individuals' adaptation to exercise training. Our study investigated the interaction of oat bran (OB) diet and moderate intensity exercise training (MIET) on skeletal muscle function and athletic performance. Studies have reinforced the positive association of high-fat diet (HFD) with chronic systemic inflammation and corresponding peripheral skeletal muscle dysfunction during exercise training. OB could alleviate the inflammation, oxidative stress, and energy homeostasis disorder associated with HFD. We observed improvement in mice limb grip strength and endurance treadmill running distance with OB intake, accompanied by regulation of muscle function-related gene expression. OB intensified exercise training-induced carbohydrate and lipid metabolism, as indicated by changes in lactate, fumarate, malate, pyruvate, succinate, and citrate levels. Additionally, specific probiotic genera producing short-chain fatty acids (SCFAs) were promoted, while inflammation-related circulating metabolites were significantly decreased with oat bran intake. Our findings suggest interactions between OB and MIET improved HFD-induced skeletal muscle dysfunction on both the phenotype and the related mechanisms. This study is an extension of our previous study on the anti-fatigue effect of oat bran, providing a novel prospective by integrating exercise adaptation, gut microbiota, molecular metabolism and skeletal muscle in situ analysis.

Exercise-induced neuroplasticity in autonomic nuclei restores the cardiac vagal tone and baroreflex dysfunction in aged hypertensive rats.

Aging is accompanied by considerable deterioration of homeostatic systems, such as autonomic imbalance characterized by heightened sympathetic activity, lower parasympathetic tone, and depressed heart rate (HR) variability, which are aggravated by hypertension. Here, we hypothesized that these age-related deficits in aged hypertensive rats can be ameliorated by exercise training, with benefits to the cardiovascular system. Therefore, male 22-mo-old spontaneously hypertensive rats (SHRs) and age-matched Wistar Kyoto (WKY) submitted to moderate-intensity exercise training (T) or kept sedentary (S) for 8 wk were evaluated for hemodynamic/autonomic parameters, baroreflex sensitivity, cardiac sympathetic/parasympathetic tone and analysis of dopamine β-hydroxylase (DBH+) and oxytocin (OT+) pathways of autonomic brain nuclei. Aged SHR-S versus WKY-S exhibited elevated mean arterial pressure (MAP: +51%) and HR (+20%), augmented pressure/HR variability, no cardiac vagal tone, and depressed reflex control of the heart (HR range, -28%; gain, -49%). SHR-T exhibited a lower resting HR, a partial reduction in the MAP (-14%), in the pressure/HR variabilities, and restored parasympathetic modulation, with improvement of baroreceptor reflex control when compared with SHR-S. Exercise training increased the ascending DBH+ projections conveying peripheral information to the paraventricular nucleus of hypothalamus (PVN), augmented the expression of OT+ neurons, and reduced the density of DBH+ neurons in the rostral ventrolateral medulla (RVLM) of SHR-T. Data indicate that exercise training induces beneficial neuroplasticity in brain autonomic circuitry, and it is highly effective to restore the parasympathetic tone, and attenuation of age-related autonomic imbalance and baroreflex dysfunction, thus conferring long-term benefits for cardiovascular control in aged hypertensive individuals.NEW & NOTEWORTHY Exercise training reduces high blood pressure and cardiovascular autonomic modulation in aged hypertensive rats. The dysfunction in the baroreflex sensitivity and impaired parasympathetic tone to the heart of aged hypertensive rats are restored by exercise training. Exercise induces beneficial neuroplasticity in the brain nuclei involved with autonomic control of cardiovascular function of aged hypertensive rats.

Effect of Exercise Training on Lipoprotein Subclass Particle Concentrations and Sizes in Older Women: Results from a Randomized Controlled Trial.

Evidence suggests that lipoprotein subclass particles are critical markers of cardiovascular disease (CVD) risk. Older women have increased CVD risk related to age. The purpose of this study was to determine whether low and moderate doses of exercise influence lipoprotein subclasses. Women (60-75 years) were randomized into groups for 16 weeks of moderate-intensity exercise training at a low or moderate dose (33.6 and 58.8 kJ/kg body weight weekly, respectively). Lipoprotein subclasses were determined by nuclear magnetic resonance spectroscopy before and after the training. The average weekly exercise duration was 109 and 164 min, for low- and moderate-dose groups, respectively. In the low-dose group, high-density lipoprotein particle (HDL-P) concentration decreased (Δ = -1.9 ± 3.1 µmol/L, mean ± SD, p = 0.002) and mean HDL-P size increased (Δ = 0.1 ± 0.3 nm, p = 0.028). In the moderate-dose group, mean HDL-P size (Δ = 0.1 ± 0.2 nm; p = 0.024) and low-density lipoprotein particle size increased (Δ = 0.4 ± 3.9 nm; p = 0.007). Baseline body mass index, peak oxygen consumption and age were associated with changes in a few lipoprotein subclasses. In this sample of inactive older women, moderate-intensity exercise training at a dose equivalent to or even lower than the minimally recommended level by public health agencies induced changes in lipoprotein subclasses in line with reduced CVD risk. However, higher doses are encouraged for greater health benefits.

Can In-Task Affect During Interval and Continuous Exercise Predict 12-Month Physical Activity Behavior? Findings from a Randomized Trial.

In-task affective responses to moderate-intensity continuous exercise training (MICT) have been shown to predict future physical activity behavior. However, limited research has investigated whether this affect-behavior relationship is similar for high-intensity interval training (HIIT) and whether it holds true over the longer term. This study aims to determine (1) if in-task affect during 2weeks of supervised MICT and HIIT predicted changes to unsupervised moderate-to-vigorous physical activity (MVPA) behavior 12months post-intervention and (2) if this predictive relationship was moderated by exercise type (MICT vs. HIIT). Ninety-nine adults (69.7% female; 50.9 ± 9.4years) who were low active and overweight were randomized to 2weeks of exercise training of MICT (n = 52) or HIIT (n = 47), followed by 12months of accelerometry-assessed free-living MVPA. The pooled moderation model was not significant, F(3, 94) = 2.54, p = .07 (R2 = 0.085), with a non-significant group by affect interaction (p = .06). The conditional effect for MICT was significant (B = 17.27, t = 2.17, p = .03), suggesting that 12-month change in MVPA increased by 17.27min/week for every one-point increase in in-task affect. The conditional effect for HIIT was not significant (p = .85), suggesting that in-task affect was not predictive of 12-month change in MVPA. The current findings raise important questions about whether the affect-behavior relationship may vary depending on exercise type. For HIIT-based exercise in particular, additional psychological constructs beyond in-task affect should be considered when attempting to predict future physical activity behavior.