Response To Exercise Research Articles

Cardiopulmonary Exercise Responses in Individuals with Metabolic Syndrome: The Ball State Adult Fitness Longitudinal Lifestyle Study

Background: The association between cardiorespiratory fitness (CRF) and metabolic syndrome (MetSyn) is well established. Additional variables derived from cardiopulmonary exercise testing (CPET) have shown prognostic value in some chronic diseases, however, there is limited information on how cardiopulmonary responses to exercise may be altered in individuals with MetSyn. Thus, the purpose of this study was to examine the association between cardiopulmonary variables derived from CPET and MetSyn. Methods: A cohort of 3181 participants (1714 men, 1467 women), aged 20-79 years, completed CPET and metabolic risk factor assessment between January 1, 1971, and November 1, 2020. Cardiopulmonary variables assessed included CRF defined as the maximum volume of oxygen uptake (VO2max), ventilatory threshold (VO2@VT), oxygen uptake efficiency slope (OUES), the ratio of ventilation to VO2 at peak exercise (peak VE/VO2) and the VE/VCO2slope. MetSyn was defined using the National Cholesterol Education Program/Adult Treatment Panel. Results: VO2max, VO2@VT, and OUES were lower (P < 0.001) and VE/VCO2slope was higher (P < 0.001) in individuals with MetSyn (n = 774), whereas no difference between groups existed for peak VE/VO2. Logistic regression analysis revealed that VO2max [0.91, 0.89-0.93; odds ratio (OR), 95% confidence interval (CI)], VO2@VT (0.91, 0.87-0.95; OR, 95% CI), OUES (0.32, 0.20-0.52; OR, 95% CI), and VE/VCO2slope (1.03, 1.01-1.05 OR, 95% CI) were all associated with the presence of MetSyn (P ≤ 0.001). Conclusion: These results indicate that MetSyn is associated with altered cardiopulomary function that may provide insight into the underlying pathophysiology of MetSyn.

Physiological response of endurance exercise as a growth hormone mediator in adolescent women's.

Overweight status decreases the growth hormone (GH) secretion, thus, increasing the risk factors for medical complications. However, proper exercise is reported to enhance GH and affect the energy balance. Therefore, exercise is proclaimed to be an accurate and engaging therapy to increase GH in preventing overweight. This study aims to investigate the physiological response of exercise in mediating the increase of GH secretion in female adolescents. 22 overweight women aged 19-20 years old, with maximal oxygen consumption of 27-35mL/kg/min, were selected as sample size. They were divided into three groups, namely (CONT, n=7) Control, (MIEE, n=7) Moderate-intensity interval endurance exercise, and (MCEE, n=8) Moderate-intensity continuous endurance exercise. The exercise was carried out by running for 30-35min using treadmills with an intensity of 60-70% HRmax. The blood sampling for GH examination was carried out four times before exercise, 10min, 6h, and 24h after exercise. The enzyme-linked immunosorbent assay (ELISA) was used to measure the GH and IGF-1 levels. The data analysis was carried out using a one-way ANOVA test, with a significance level of 5%. The results of the one-Way ANOVA test suggested a significantly different average GH and IGF-1 before and after the exercise between the three groups (CON, MIEE, and MCEE) (p≤0.05). MCEE increases the GH and IGF-1 levels more considerably than MIEE. Therefore, exercise is a mediator to increase GH and IGF-1 secretion in overweight individuals. Exercise could be a viable therapy for overweight people.

Wearing a surgical mask: Effects on gas exchange and hemodynamic responses during maximal exercise.

The importance of using masks during exercise has increased since the coronavirus disease‐2019 (COVID‐19). This study aimed to investigate the effects of using surgical masks on gas exchange and exercise responses in maximal exercise. Twenty‐six participants were included. Participants performed the maximal exercise tests twice, masked, and unmasked. Gas exchange parameters (at maximal exercise and anaerobic threshold [AT]) and hemodynamic responses were measured. In the hemodynamic responses measured at rest, only the saturation of peripheral oxygen (SpO2) was lower in the masked (mean: 97.23 ± 1.33%) measurement than in the unmasked (mean: 97.96 ± 1.07%) measurement (p = 0.006). Test duration was lower in the masked test (unmasked: 10.32 ± 1.36 min vs. masked: 10.03 ± 1.42 min, p = 0.030). Peak oxygen consumption (VO2peak) (unmasked: 31.23 ± 5.37 vs. masked: 27.03 ± 6.46 ml/kg/min), minute ventilation (VE) l/min, and energy expenditure (EE) kcal/hour were higher in unmasked tests (p < 0.001). There was no difference in the gas exchange parameters measured at the AT in the masked and unmasked tests (p > 0.05). Respiratory gas exchange parameters were affected in peak exercise due to increased respiratory workload, but not at the AT. There was no change in hemodynamic responses because vascular control may not be affected by mask usage.

Exercise Responsiveness in Obese Adults

Obesity is associated with several skeletal muscle impairments which can be improved through an aerobic exercise prescription. The possibility that exercise responsiveness is diminished in people with obesity has been suggested but not well‐studied.PURPOSEThe purpose of this study was to investigate how obesity influences acute exercise responsiveness within skeletal muscle.METHODSNon‐obese (NO; n=19; 10F/9M; BMI=25.1 ± 2.8 kg/m2) and Obese (O; n=21; 14F/7M; BMI=37.3 ± 4.6 kg/m2) adults performed 30 minutes of single‐leg cycling at 70% of VO2peak. Serial muscle biopsies (vastus lateralis) were collected before exercise and 3 and 6 hours post‐exercise to measure protein synthesis and gene expression.RESULTSThe exercise‐induced fold change in mixed muscle protein synthesis trended (p=0.058) higher in NO (1.28 ± 0.54‐fold) compared to O (0.95 ± 0.42‐fold) and was inversely related to BMI (r=‐.374, p=0.027). RNA sequencing revealed 331 and 280 genes that were up or downregulated after exercise in NO and O, respectively. Gene set enrichment analysis showed O had blunted post‐exercise pathways related to MAPK signaling, chemokine‐mediated signaling, FC receptor mediated stimulation signaling, cell proliferation, apoptosis, and RNA polymerase II promotion. Quantitative polymerase chain reaction of select metabolic (PGC1a, PGC1b, TFAM, PDK4, IRS, MAPK, and PRKAA1) and muscle growth (SLC, TBC, MSTN, MyoD, TRIM32, FOX03, and FBXO3) genes were similar between groups 3 and 6 hours after exercise.ConclusionThese data highlight several unique pathways in individuals with obesity that result in a blunted exercise response.

Cholinergic‐mediated Circulatory Responses at the Onset of Isometric Exercise: Does Sex Matter?

IntroductionWe have shown that handgrip exercise evokes an initial decrease in systemic vascular resistance (SVR), which was abolished by cholinergic blockade (glycopyrrolate) and, thereby, augmented the blood pressure (BP) response. These findings suggest that a cholinergic mechanism is important for the BP and SVR responses at the onset of isometric handgrip exercise in humans. Noteworthy, this previous study included men only, and was not designed to investigate the potential existence of sex‐related differences in immediate BP and circulatory responses evoked at the exercise onset. Given this, the aim of this study was to test the hypothesis that women present an attenuated fall in SVR and increased pressor response compared to men at the onset of isometric handgrip exercise due to a blunted cholinergic vasodilation.MethodsTen healthy men (aged 21 ± 1 year) and 10 women (aged 24 ± 1 year) were recruited. Women were non‐oral contraceptives users and performed experiments in the early follicular phase of the menstrual cycle. Participants performed 20s bout of isometric handgrip exercise at 40% of maximal voluntary contraction. Beat‐to‐beat heart rate (HR) (ECG) and mean BP (finger photopletysmography) were continuously measured. Beat‐to‐beat stroke volume (SV) was obtained with the Modelflow method and matched with HR to estimate cardiac output (CO) and SVR. The exercise responses were expressed as a change from 10s immediately before the onset of voluntary contraction.ResultsThe BP response pattern appeared to be different between men and women at the onset of isometric exercise. While men presented a typical exercise‐evoked biphasic BP response (3s: Δ2 ± 2 mmHg; 10s: Δ1 ± 1 mmHg; 20s: Δ5 ± 3 mmHg), women showed a progressive increase in mean BP (3s: Δ1 ± 1 mmHg; 10s; Δ3 ± 1 mmHg; 20s: Δ6 ± 1 mmHg; P=0.681). Men demonstrated a decrease in SVR at 3s (Δ‐0.9 ± 0.3 mmHg.L‐1.min), 10s (Δ ‐1.6 ± 0.4 mmHg.L‐1.min) and 20s (Δ‐1.9 ± 0.7 mmHg.L‐1.min) following the exercise onset, and these responses tended to be attenuated in women (3s: Δ‐0.3 ± 0.3 mmHg.L‐1.min; 10s: Δ‐1.2 ± 0.4 mmHg.L‐1.min; 20s: Δ‐0.6 ± 0.5 mmHg.L‐1.min; P=0.131). There were no sex differences in HR, SV and CO responses to exercise.ConclusionThese findings suggest a lack of sex differences in immediate BP and circulatory responses at the onset of isometric handgrip exercise, indicative of similar cholinergic‐mediated vasodilation in skeletal muscle between men and women.

Exercise and Hypercapnia Differentially Modify Ratios of Extracranial and Intracranial Pulsatility

INTRODUCTIONDamping of pulsatile flow between extracranial and intracranial cerebral arteries is an essential allostatic mechanism protecting cerebral microvessels from recalcitrant hemodynamics. The ratio of pulsatility between proximal and distal cerebral arteries may provide a measure of cerebrovascular hemodynamic damping. This might prove useful as an evaluation of cerebrovascular regulation in response to pulsatile perturbations.PURPOSETo characterize cerebral pulsatile damping between extracranial and intracranial environments in response to perturbations eliciting matched shear stress, such as exercise and hypercapnia.METHODSParticipants (n=10) completed two 30‐min experimental conditions aimed at matching cerebral artery shear stress, each separated by 48 hrs: (1) mild hypercapnia (CO2; FICO2:0.045) and (2) submaximal cycling (EX; 60%HRreserve). Cerebral pulsatility index (PI: (systolic velocity‐diastolic velocity)/mean velocity)) was assessed at baseline, during, and following each condition in the internal carotid artery (ICA) and middle cerebral artery (MCA) using Doppler ultrasound. Heart rate (HR) and blood pressure (BP) were assessed continuously using ECG and photoplethysmography, respectively. Cerebral pulsatile damping was calculated: (ICA PI / MCA PI) to investigate ratios of cerebral pulsatile hemodynamics between extracranial and intracranial arteries.RESULTSCerebral pulsatile damping was greater during CO2 (1.66 ± 0.31) than EX (1.22 ± 0.35) (time*condition effect, p=0.002). The change in cerebral pulsatile damping was related to the change in heart rate (r = ‐0.70, p = 0.04), but not BP between baseline and the experimental conditions.CONCLUSIONSAs evidenced by the response in cerebral pulsatile damping, exercise and hypercapnia result in different ratios of extracranial to intracranial pulsatility despite inducing similar vasodilation when shear stress was matched. This might in part be explained by differences in HR between conditions. Further research is important to elucidate the mechanisms behind the deviance in hemodynamic responses.

Associations between aerobic exercise and dopamine-related reward-processing: Informing a model of human exercise engagement

Endurance or aerobic exercise has many physical and mental health benefits, but less is known about the specific impact that cardiovascular activity may have on dopamine-associated brain circuits involved in reward processing and mood regulation in humans. Understanding such effects will help to explain individual differences in both exercise uptake and maintenance. This study evaluated neural response to a classical taste-conditioning reward prediction error task with the use of functional magnetic resonance imaging, along with data on self-reported aerobic exercise among healthy young adult females (N = 111). Results indicated positive associations between reported aerobic exercise and regional brain response that remained significant after multiple comparison correction for the right medial orbital frontal cortex response to unexpected sucrose receipt (r = 0.315, p = .0008). The medial orbitofrontal cortex is implicated in reward and outcome value computation and the results suggest that aerobic exercise may strengthen this circuitry, or reciprocally, higher orbitofrontal cortical activity may reinforce exercise behavior. The findings aid in developing a model of how exercise engagement can modify reward-circuit function and could be used therapeutically in conditions associated with altered brain salience response.

Cerebrovascular Dynamics During Light Exercise

Cerebral blood flow (CBF) dynamic response to moderate‐intensity exercise has a time delay (TD) of ~ 40s. This is dramatically longer compared to other physiological responses to exercise (e.g. skeletal muscle blood flow &lt;10 s) and CBF response to other stimuli (e.g. hypercapnia, thigh cuff occlusion, ~ 10‐20 s). A possible explanation is that a rest‐to‐exercise transition induces a brief hypotensive response due to intensity dependent rapid vasodilation of the periphery (exercise‐onset hypotension, EoH).PurposeTo determine if the magnitude and timing of EoH, effectively reduces CBF at exercise onset causing the longer observed TD. To test this, we modelled CBF kinetic response to light‐intensity exercise to mitigate the magnitude of EoH and determine if components of the CBF response were quickened in young healthy adults.Methods26 young healthy adults (13 Women, 23.8 ± 4 yrs; 23.9 ± 2.9 kg/m2) completed a rest (2min seated quietly, BL) to exercise (3 minutes at 50W, EX) transition on a recumbent cycle ergometer. Middle cerebral artery velocity (MCAv; transcranial doppler) and mean arterial pressure (MAP; finger photoplethysmography) were measured on a heartbeat‐by‐heartbeat basis. End‐tidal CO2 (EtCO2) was measured using breath‐by‐breath capnography. Cerebral vascular conductance index (CVCi) was calculated as (CVCi = MCAv/MAP *100 mmHg). Change in MCAv data (ΔMCAv = MCAvEX‐MCAvBL) were averaged into 2 s bins and fit to a monoexponential model (ΔMCAv(t)= Amp(1‐e‐(t‐TD)/ τ)). Time delay (TD), tau (τ), and mean response time (MRT = TD + τ) were obtained from the model. Several subjects (N=11) exhibited little to no TD (TD &lt; 1 s), these subjects (FAST) were separated out and compared to individuals with longer TDs (TD ≥ 3 s; SLOW). Comparisons were made using an independent t‐test.ResultsAll data is mean±SD. In total, subjects exhibited a TD of 15.4 ± 18.2 s, τ of 79.8 ± 139.7, and MRT of 95.3 ± 134.9 s. This coincided with a ΔMAPNADIR (‐14.5 ± 8.2 mmHg), ΔMCAvNADIR (‐5.7 ± 5.8 cm/s) which occurred at similar times (14.0 ± 17.2 vs. 18.6 ± 14.4 s; p=0.30 MAPNADIR vs. MCAvNADIR), and ΔCVCiMAX (25.3 ± 34.0 cm/s/100mmHg). When data were split, the FAST group experienced a faster TD compared to SLOW (0.01 ± 0.01 vs. 26.8 ± 16.4 s; p&lt;0.001). ΔMCAvNADIR although different (‐1.0 ± 4.0 vs. ‐9.1 ± 4.2 cm/s; p&lt;0.001, FAST vs. SLOW), occurred at similar times (20.5 ± 17.3 vs. 17.3 ± 12.5 s; p=0.59, FAST vs. SLOW). ΔMAPNADIR (‐14.4 ± 10.4 vs. ‐14.6 ± 6.5 mmHg; p=0.97) and CVCiMAX (22.1 ± 25.4 vs. 27.6 ± 39.9 cm/s/100mmHg; p=0.56 FAST vs. SLOW) were not different between groups. There were no other differences between groups regrading demographic, EtCO2, or other kinetic variables.DiscussionOur data indicates EoH is related to the initial drop in CBF and TD during light‐exercise is faster (15.9 s) when compared to previous research during moderate‐intensity exercise (~40 s). However, our data identifies fast responders who have minimal TD and MCAvNADIR responses without differing EoH at the same absolute exercise intensity. Therefore, these data reveal monoexponential CBF models ignore initial perturbances to CBF and disregard potentially important cerebrovascular mechanisms occurring prior to model predicted blood flow increases.

Mitochondrial mutations alter endurance exercise response and determinants in mice

Primary mitochondrial diseases (PMDs) are a heterogeneous group of metabolic disorders that can be caused by hundreds of mutations in both mitochondrial DNA (mtDNA) and nuclear DNA (nDNA) genes. Current therapeutic approaches are limited, although one approach has been exercise training. Endurance exercise is known to improve mitochondrial function in heathy subjects and reduce risk for secondary metabolic disorders such as diabetes or neurodegenerative disorders. However, in PMDs the benefit of endurance exercise is unclear, and exercise might be beneficial for some mitochondrial disorders but contraindicated in others. Here we investigate the effect of an endurance exercise regimen in mouse models for PMDs harboring distinct mitochondrial mutations. We show that while an mtDNA ND6 mutation in complex I demonstrated improvement in response to exercise, mice with a CO1 mutation affecting complex IV showed significantly fewer positive effects, and mice with an ND5 complex I mutation did not respond to exercise at all. For mice deficient in the nDNA adenine nucleotide translocase 1 (Ant1), endurance exercise actually worsened the dilated cardiomyopathy. Correlating the gene expression profile of skeletal muscle and heart with the physiologic exercise response identified oxidative phosphorylation, amino acid metabolism, matrisome (extracellular matrix [ECM]) structure, and cell cycle regulation as key pathways in the exercise response. This emphasizes the crucial role of mitochondria in determining the exercise capacity and exercise response. Consequently, the benefit of endurance exercise in PMDs strongly depends on the underlying mutation, although our results suggest a general beneficial effect.

Skeletal muscle properties show collagen organization and immune cell content are associated with resistance exercise response heterogeneity in older persons.

In older individuals, hypertrophy from progressive resistance training (PRT) is compromised in approximately one-third of participants in exercise trials. The objective of this study was to establish novel relationships between baseline muscle features and/or their PRT-induced change in vastus lateralis muscle biopsies with hypertrophy outcomes. Multiple linear regression analyses adjusted for sex were performed on phenotypic data from older adults (n = 48 participants, 70.8 ± 4.5 yr) completing 14 wk of PRT. Results show that baseline muscle size associates with growth regardless of hypertrophy outcome measure [fiber cross-sectional area (fCSA), β = -0.76, Adj. P < 0.01; thigh muscle area by computed tomography (CT), β = -0.75, Adj. P < 0.01; dual-energy X-ray absorptiometry (DXA) thigh lean mass, β = -0.47, Adj. P < 0.05]. Furthermore, loosely packed collagen organization (CO, β = -0.44, Adj. P < 0.05) and abundance of CD11b+/CD206- immune cells (β = -0.36, Adj. P = 0.10) were negatively associated with whole muscle hypertrophy, with a significant sex interaction on the latter. In addition, a composite hypertrophy score generated using all three measures reinforces significant fiber level findings that changes in myonuclei (MN) (β = 0.67, Adj. P < 0.01), changes in immune cells (β = 0.48, Adj. P < 0.05; both CD11b+/CD206+and CD11b+/CD206- cells), and capillary density (β = 0.56, Adj. P < 0.01) are significantly associated with growth. Exploratory single-cell RNA-sequencing of CD11b+ cells in muscle in response to resistance exercise showed that macrophages have a mixed phenotype. Collagen associations with macrophages may be an important aspect in muscle response heterogeneity. Detailed histological phenotyping of muscle combined with multiple measures of growth response to resistance training in older persons identify potential new mechanisms underlying response heterogeneity and possible sex differences.NEW & NOTEWORTHY Extensive analyses of muscle features associated with muscle size and resistance training response in older persons, including sex differences, and evaluation of multiple measures of hypertrophy are discussed. Collagen organization and CD11b-expressing immune cells offer potential new targets to augment growth response in older individuals. A hypertrophy composite score reveals that changes in immune cells, myonuclei, and capillary density are critically important for overall muscle growth while sc-RNAseq reveals evidence for macrophage heterogeneity.

A HIF-1 signature dominates the attenuation in the human skeletal muscle transcriptional response to high-intensity interval training.

High-intensity interval training (HIIT) generates profound metabolic adaptations in skeletal muscle. These responses mirror performance improvements but follow a nonlinear pattern comprised of an initial fast phase followed by a gradual plateau effect. The complete time-dependent molecular sequelae that regulates this plateau effect remains unknown. We hypothesize that the plateau effect during HIIT is restricted to specific pathways with communal upstream transcriptional regulation. To investigate this, 11 healthy men performed nine sessions of HIIT [10 × 4 min of cycling at 91% of maximal heart rate (HRmax)] over a 3-wk period. Before and 3 h after the 1st and 9th exercise bout, skeletal muscle biopsies were obtained, and RNA sequencing was performed. Almost 2,000 genes across 84 pathways were differentially expressed in response to a single HIIT session. The overall transcriptional response to acute exercise was strikingly similar at 3 wk, 83% (n = 1,650) of the genes regulated after the 1st bout of exercise were similarly regulated by the 9th bout, albeit with a smaller effect size, and the response attenuated to on average 70% of the 1st bout. The attenuation differed substantially between pathways and was especially pronounced for glycolysis and cellular adhesion compared to, e.g., MAPK and vascular endothelial growth factor (VEGF)-A signaling. The attenuation was driven by a combination of changes in steady-state expression and specific transcriptional regulation. Given that the exercise intensity was progressively increased, and the attenuation was pathway-specific, we suggest that moderation of muscular adaptation after a period of training stems from targeted regulation rather than a diminished exercise stimulus.NEW & NOTEWORTHY This is the first study to address the phenomena of attenuation of the acute exercise response on a global genomic scale with a focus on underlying regulatory machinery and it is, to the best of our knowledge, the first study conducted in humans was exercise-induced regulation of different canonical pathways and transcription factors are contrasted with regards to attenuation after a period with regular exercise training. These results provide evidence for a pathway-specific regulated augmentation of the response to acute exercise over time that tracks with the successive adaptation on the systemic level.

Impact of obesity on the molecular response to a single bout ofexercise in a preliminary human cohort.

The health benefits of exercise are well documented, but several exercise-response parameters are attenuated in individuals with obesity. The goal of this pilot study was to identify molecular mechanisms that may influence exercise response with obesity. A multi-omics comparison of the transcriptome, proteome, and phosphoproteome in muscle from a preliminary cohort of lean individuals (n=4) and individuals with obesity (n=4) was performed, before and after a single bout of 30 minutes of unilateral cycling at 70% maximal oxygen uptake (VO2 peak). Mass spectrometry and RNA sequencing were used to interrogate the proteome, phosphoproteome, and transcriptome from muscle biopsy tissue. The main findings are that individuals with obesity exhibited transcriptional and proteomic signatures consistent with reduced mitochondrial function, protein synthesis, and glycogen synthesis. Furthermore, individuals with obesity demonstrated markedly different transcriptional, proteomic, and phosphoproteomic responses to exercise, particularly biosynthetic pathways of glycogen synthesis and protein synthesis. Casein kinase II subunit alpha and glycogen synthase kinase-3β signaling was identified as exercise-response pathways that were notably altered by obesity. Opportunities to enhance exercise responsiveness by targeting specific molecular pathways that are disrupted in skeletal muscle from individuals with obesity await a better understanding of the precise molecular mechanisms that may limit exercise-response pathways in obesity.

Effect of acute high-intensity exercise on myocardium metabolic profiles in rat and human study via metabolomics approach

Acute high-intensity exercise can affect cardiac health by altering substance metabolism. However, few metabolomics-based studies provide data on the effect of exercise along with myocardial metabolism. Our study aimed to identify metabolic signatures in rat myocardium during acute high-intensity exercise and evaluate their diagnostic potential for sports injuries. We collected rat myocardium samples and subjects’ serum samples before and after acute high-intensity exercise for metabolite profiling to explore metabolic alterations of exercise response in the myocardium. Multivariate analysis revealed myocardium metabolism differed before and after acute high-intensity exercise. Furthermore, 6 target metabolic pathways and 12 potential metabolic markers for acute high-intensity exercise were identified. Our findings provided an insight that myocardium metabolism during acute high-intensity exercise had distinct disorders in complex lipids and fatty acids. Moreover, an increase of purine degradation products, as well as signs of impaired glucose metabolism, were observed. Besides, amino acids were enhanced with a certain protective effect on the myocardium. In this study, we discovered how acute high-intensity exercise affected myocardial metabolism and exercise-related heart injury risks, which can provide references for pre-competition screening, risk prevention, and disease prognosis in competitive sports and effective formulation of exercise prescriptions for different people.

The HERITAGE Family Study: A Review of the Effects of Exercise Training on Cardiometabolic Health, with Insights into Molecular Transducers.

ABSTRACTThe aim of the HERITAGE Family Study was to investigate individual differences in response to a standardized endurance exercise program, the role of familial aggregation, and the genetics of response levels of cardiorespiratory fitness and cardiovascular disease and diabetes risk factors. Here we summarize the findings and their potential implications for cardiometabolic health and cardiorespiratory fitness. It begins with overviews of background and planning, recruitment, testing and exercise program protocol, quality control measures, and other relevant organizational issues. A summary of findings is then provided on cardiorespiratory fitness, exercise hemodynamics, insulin and glucose metabolism, lipid and lipoprotein profiles, adiposity and abdominal visceral fat, blood levels of steroids and other hormones, markers of oxidative stress, skeletal muscle morphology and metabolic indicators, and resting metabolic rate. These summaries document the extent of the individual differences in response to a standardized and fully monitored endurance exercise program and document the importance of familial aggregation and heritability level for exercise response traits. Findings from genomic markers, muscle gene expression studies, and proteomic and metabolomics explorations are reviewed, along with lessons learned from a bioinformatics-driven analysis pipeline. The new opportunities being pursued in integrative -omics and physiology have extended considerably the expected life of HERITAGE and are being discussed in relation to the original conceptual model of the study.

Can exhaled volatile organic compounds differentiate high and low responders to resistance exercise?

Participation in resistance training improves muscle strength and size, as well as reduced risk of chronic disease and frailty. However, the exercise response to resistance training is highly variable. In part this may be attributed to individual physiological differences. Identification of biomarkers that can distinguish between high and low responders to exercise are therefore of interest. Exhaled volatile organic compounds may provide a non-invasive method of monitoring the physiological response to resistance training. However, the relationship between exhaled organic compounds and the acute response to resistance exercise is not fully understood. Therefore, this research will investigate exhaled volatile organic compounds in acute response to resistance exercise with an aim to discover a common group of compounds that can predict high and low responders to standardised resistance training.

Exercise, Physical Activity, and Cardiometabolic Health: Pathophysiologic Insights.

Physical activity and its sustained and purposeful performance-exercise-promote a broad and diverse set of metabolic and cardiovascular health benefits. Regular exercise is the most effective way to improve cardiorespiratory fitness, a measure of one's global cardiovascular, pulmonary and metabolic health, and one of the strongest predictors of future health risk. Here, we describe how exercise affects individual organ systems related to cardiometabolic health, including the promotion of insulin and glucose homeostasis through improved efficiency in skeletal muscle glucose utilization and enhanced insulin sensitivity; beneficial changes in body composition and adiposity; and improved cardiac mechanics and vascular health. We subsequently identify knowledge gaps that remain in exercise science, including heterogeneity in exercise responsiveness. While the application of molecular profiling technologies in exercise science has begun to illuminate the biochemical pathways that govern exercise-induced health promotion, much of this work has focused on individual organ systems and applied single platforms. New insights into exercise-induced secreted small molecules and proteins that impart their effects in distant organs ("exerkines") highlight the need for an integrated approach towards the study of exercise and its global effects; efforts that are ongoing.

49. LOSS OF HYPOXIA SIGNALING LIMITS PHYSIOLOGIC AND MUSCLE ADAPTATIONS TO AEROBIC EXERCISE IN AGING

PURPOSE: This study investigates signaling pathways which contribute to aging associated loss of muscle adaptation to exercise. METHODS: Young (Y, 12 weeks) and Old (O, 25 months) mice were subjected to regimented treadmill running or no exercise for 8 weeks. Mice were then subjected to muscle physiology testing. The transcriptional response to exercise was evaluated using RNA Seq. A genetically modified mouse model, with a deletion of aryl hydrocarbon receptor nuclear translocator (ARNT) was then evaluated for response to exercise training as it mimics old mice with regards to transcription profile and exercise response. RESULTS: Y, trained mice experienced a significant increase in distance running, speed, and lean muscle mass in comparison to untrained controls. O mice did not improve significantly in these measures. Transcriptome analysis in muscle from Y mice demonstrated differential regulation of 96 genes with exercise. None of these genes were similarly regulated in the O group. Genes most upregulated in Y mice are targets of hypoxia signaling. ARNT, a regulator of hypoxia signaling, increased 3-fold with exercise in Y mice, but not in O mice following exercise. To assess whether loss of ARNT impairs the exercise response, we generated a mouse with muscle-specific knockout of ARNT (ARNT muscle (mKO). Following regimented exercise, ARNT mKO mice did not improve maximal distance running, maximal running speed, or lean muscle mass. Administration of an ARNT agonist restored the exercise response. CONCLUSION: Restoration of ARNT and hypoxia signaling may restore the physiologic response to exercise in aging.

Exercise response on dose curve among class I obese young adult population.

To identify exercise regimes having a short duration and yet incorporating the effects of both aerobic and resistance exercises. The randomised study was conducted from December 1, 2019, to April 31, 2020, at Ziauddin Hospital, Karachi, and comprised individuals of either gender aged 20-40 years with class-I obesity. All participants were initially screened using a physical activity and readiness questionnaire to determine if they were fit to perform the exercises. Subsequently, dynamic exercises were introduced based on the guidelines of the American College of Sports Medicine. The subjects were randomised into aerobic group A, resistance group B and dynamic resistance group C. The intervention lasted 12 weeks. The quantification of exercises was done using the frequency, intensity, time, and type protocol. The results were analysed on MedCalc statistical software. Out of the 102 participants, 51(50%) each were males and females. Each of the three groups had 34(33.3%) subjects; 17(50%) males and as many females. The impact was significant in all the three groups (p<0.05). The effect was significantly better in group C than groups A and B. Body mass index and body fat percentage values improved through aerobic, resistance and dynamic resistance exercises.

The Dose-Response of the Nordic Hamstring Exercise on Biceps Femoris Architecture and Eccentric Knee Flexor Strength: A Randomized Interventional Trial.

To examine the dose-response of the Nordic hamstring exercise (NHE) on biceps femoris long head (BFlh) architecture and eccentric knee flexor strength. Randomized interventional trial. Forty recreationally active males completed a 6-week NHE training program consisting of either intermittent low volumes (group 1; n = 10), low volumes (group 2; n = 10), initial high volumes followed by low volumes (group 3; n = 10), or progressively increasing volumes (group 4; n = 10). A 4-week detraining period followed each program. Muscle architecture was assessed weekly during training and after 2 and 4weeks of detraining. Eccentric knee flexor strength was assessed preintervention and postintervention and after 2 and 4weeks of detraining. Following 6weeks of training, BFlh fascicle length (FL) increased in group 3 (mean difference = 0.83cm, d = 0.45, P = .027, +7%) and group 4 (mean difference = 1.48cm, d = 0.94, P = .004, +14%). FL returned to baseline following detraining in groups 3 and 4. Strength increased in group 2 (mean difference = 53.6N, d = 0.55, P = .002, +14%), group 3 (mean difference = 63.4N, d = 0.72, P = .027, +17%), and group 4 (mean difference = 74.7, d = 0.83, P = .006, +19%) following training. Strength returned to baseline following detraining in groups 2 and 3 but not in group 4. Initial high volumes of the NHE followed by lower volumes, as well as progressively increasing volumes, can elicit increases in BFlh FL and eccentric knee flexor strength. Low volumes of the NHE were insufficient to increase FL, although as few as 48 repetitions in 6 weeks did increase strength.

Association of Cerebral Oxygenation During Exercise With Target Organ Damage in Middle-Aged Hypertensive and Normotensive Individuals.

The brain is one of the main target organs affected by hypertension. Impaired cerebral oxygenation during exercise is an indicator of cerebral dysfunction. We aimed to investigate whether cerebral oxygenation during exercise correlates with subclinical markers of early target organ damage in a population of middle-aged, newly diagnosed hypertensive and healthy individuals. Carotid intima-media thickness (cIMT) was measured using ultrasound, arterial stiffness was estimated measuring the augmentation index and pulse wave velocity, and retinal vessel diameter was assessed via the central retinal-arteriolar and vein equivalent and retinal-arteriovenous ratio. Participants (n = 93) performed a 3-minute isometric handgrip exercise. Cerebral prefrontal oxygenation was measured continuously using near infrared spectroscopy. The average exercise responses in oxygenated hemoglobin (O2Hb), deoxygenated hemoglobin (HHb), and total hemoglobin (tHb) were assessed. Univariate analyses were performed; partial correlation was used to account for traditional cardiovascular risk factors to identify independent associations between cerebral-oxygenation indices and early markers of target organ damage. Mean cIMT was negatively correlated with the average exercise response in cerebral oxygenation (rhoO2Hb = -0.348, PO2Hb = 0.001; rhotHb = -0.253, Pthb = 0.02). Augmentation index was negatively correlated with cerebral oxygenation during exercise (rhoO2Hb = -0.374, P < 0.001; rhotHb = -0.332, P = 0.02), whereas no significant correlation was observed between pulse wave velocity and cerebral-oxygenation indices. In the adjusted analysis, cerebral oxygenation was correlated with central retinal arteriolar diameter (CRAE r = 0.233, P = 0.043). Our novel findings suggest that indices of lower cerebral oxygenation during a submaximal physical task are associated with markers of early, subclinical target organ damage, namely increased cIMT, arterial stiffness, and arteriolar retinal narrowing in newly diagnosed, untreated, hypertensive individuals.