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The methylome and transcriptome signatures following exercise that are physiologically and metabolically relevant to sporting contexts such as team sports or health prescription scenarios (e.g., high intensity interval training/HIIT) has not been investigated. To explore this, we performed two different sport/exercise relevant high-intensity running protocols in five male sport team members using a repeated measures design of: (1) change of direction (COD) versus; (2) straight line (ST) running exercise with a wash-out period of at least 2 weeks between trials. Skeletal muscle biopsies collected from the vastus lateralis 30 min and 24 h post exercise, were assayed using 850K methylation arrays and a comparative analysis with recent (subject-unmatched) sprint and acute aerobic exercise meta-analysis transcriptomes was performed. Despite COD and ST exercise being matched for classically defined intensity measures (speed × distance and number of accelerations/decelerations), COD exercise elicited greater movement (GPS-Playerload), physiological (HR), metabolic (lactate) as well as central and peripheral (differential RPE) exertion measures compared with ST exercise, suggesting COD exercise evoked a higher exercise intensity. The exercise response alone across both conditions evoked extensive alterations in the methylome 30 min and 24 h post exercise, particularly in MAPK, AMPK and axon guidance pathways. COD evoked a considerably greater hypomethylated signature across the genome compared with ST exercise, particularly at 30 min post exercise, enriched in: Protein binding, MAPK, AMPK, insulin, and axon guidance pathways. Comparative methylome analysis with sprint running transcriptomes identified considerable overlap, with 49% of genes that were altered at the expression level also differentially methylated after COD exercise. After differential methylated region analysis, we observed that VEGFA and its downstream nuclear transcription factor, NR4A1 had enriched hyp

The methylome and transcriptome signatures following exercise that are physiologically and metabolically relevant to sporting contexts such as team sports or health prescription scenarios (e.g., high intensity interval training/HIIT) has not been investigated. To explore this, we performed two different sport/exercise relevant high-intensity running protocols in five male sport team members using a repeated measures design of: (1) change of direction (COD) versus; (2) straight line (ST) running exercise with a wash-out period of at least 2 weeks between trials. Skeletal muscle biopsies collected from the vastus lateralis 30 min and 24 h post exercise, were assayed using 850K methylation arrays and a comparative analysis with recent (subject-unmatched) sprint and acute aerobic exercise meta-analysis transcriptomes was performed. Despite COD and ST exercise being matched for classically defined intensity measures (speed × distance and number of accelerations/decelerations), COD exercise elicited greater movement (GPS-Playerload), physiological (HR), metabolic (lactate) as well as central and peripheral (differential RPE) exertion measures compared with ST exercise, suggesting COD exercise evoked a higher exercise intensity. The exercise response alone across both conditions evoked extensive alterations in the methylome 30 min and 24 h post exercise, particularly in MAPK, AMPK and axon guidance pathways. COD evoked a considerably greater hypomethylated signature across the genome compared with ST exercise, particularly at 30 min post exercise, enriched in: Protein binding, MAPK, AMPK, insulin, and axon guidance pathways. Comparative methylome analysis with sprint running transcriptomes identified considerable overlap, with 49% of genes that were altered at the expression level also differentially methylated after COD exercise. After differential methylated region analysis, we observed that VEGFA and its downstream nuclear transcription factor, NR4A1 had enriched hyp

We investigated whether diurnal differences in muscle force output are associated with the post-translational state of muscle proteins. Ten physically active men (mean ± SD; age 26.7 ± 3.7 y) performed experimental sessions in the morning (08:00 h) and evening (17:00 h), which were counterbalanced in order of administration and separated by at least 72 h. Knee extensor maximal voluntary isometric contraction (MVIC) force and peak rate of force development (RFD) were measured, and samples of vastus lateralis were collected immediately after exercise. MVIC force was greater in the evening (mean difference of 67 N, 10.2%; p < 0.05). Two-dimensional (2D) gel analysis encompassed 122 proteoforms and discovered 6 significant (p < 0.05; false discovery rate [FDR] = 10%) diurnal differences. Phosphopeptide analysis identified 1693 phosphopeptides and detected 140 phosphopeptides from 104 proteins that were more (p < 0.05, FDR = 22%) phosphorylated in the morning. Myomesin 2, muscle creatine kinase, and the C-terminus of titin exhibited the most robust (FDR < 10%) diurnal differences. Exercise in the morning, compared to the evening, coincided with a greater phosphorylation of M-band-associated proteins in human muscle. These protein modifications may alter the M-band structure and disrupt force transmission, thus potentially explaining the lower force output in the morning.

We investigated whether diurnal differences in muscle force output are associated with the post-translational state of muscle proteins. Ten physically active men (mean ± SD; age 26.7 ± 3.7 y) performed experimental sessions in the morning (08:00 h) and evening (17:00 h), which were counterbalanced in order of administration and separated by at least 72 h. Knee extensor maximal voluntary isometric contraction (MVIC) force and peak rate of force development (RFD) were measured, and samples of vastus lateralis were collected immediately after exercise. MVIC force was greater in the evening (mean difference of 67 N, 10.2%; p < 0.05). Two-dimensional (2D) gel analysis encompassed 122 proteoforms and discovered 6 significant (p < 0.05; false discovery rate [FDR] = 10%) diurnal differences. Phosphopeptide analysis identified 1693 phosphopeptides and detected 140 phosphopeptides from 104 proteins that were more (p < 0.05, FDR = 22%) phosphorylated in the morning. Myomesin 2, muscle creatine kinase, and the C-terminus of titin exhibited the most robust (FDR < 10%) diurnal differences. Exercise in the morning, compared to the evening, coincided with a greater phosphorylation of M-band-associated proteins in human muscle. These protein modifications may alter the M-band structure and disrupt force transmission, thus potentially explaining the lower force output in the morning.

Context: The mechanisms responsible for dietary fat-induced insulin resistance of skeletal muscle and its microvasculature are only partially understood.Objective: To determine the impact of high-fat overfeeding on postprandial glucose fluxes, muscle insulin signaling, and muscle microvascular endothelial nitric oxide synthase (eNOS) content and activation.Design: Fifteen non-obese volunteers consumed a high-fat (64%) high-energy (+47%) diet for 7 days. Experiments were performed before and after the diet. Stable isotope tracers were used to determine glucose fluxes in response to carbohydrate plus protein ingestion. Muscle insulin signaling was determined as well as the content and activation state of muscle microvascular eNOS.Results: High-fat overfeeding impaired postprandial glycemic control as demonstrated by higher concentrations of glucose (+11%; P = 0.004) and insulin (+19%; P = 0.035). Carbohydrate plus protein ingestion suppressed endogenous glucose production to a similar extent before and after the diet. Conversely, high-fat overfeeding reduced whole-body glucose clearance (-16%; P = 0.021) and peripheral insulin sensitivity (-26%; P = 0.006). This occurred despite only minor alterations in skeletal muscle insulin signaling. High-fat overfeeding reduced eNOS content in terminal arterioles (P = 0.017) and abolished the increase in eNOS Ser(1177) phosphorylation that was seen after carbohydrate plus protein ingestion.Conclusion: High-fat overfeeding impaired whole-body glycemic control due to reduced glucose clearance, not elevated endogenous glucose production. The finding that high-fat overfeeding abolished insulin-mediated eNOS Ser(1177) phosphorylation in the terminal arterioles suggests that impairments in the vasodilatory capacity of the skeletal muscle microvasculature may contribute to early dietary fat-induced impairments in glycemic control.

Context: The mechanisms responsible for dietary fat-induced insulin resistance of skeletal muscle and its microvasculature are only partially understood.Objective: To determine the impact of high-fat overfeeding on postprandial glucose fluxes, muscle insulin signaling, and muscle microvascular endothelial nitric oxide synthase (eNOS) content and activation.Design: Fifteen non-obese volunteers consumed a high-fat (64%) high-energy (+47%) diet for 7 days. Experiments were performed before and after the diet. Stable isotope tracers were used to determine glucose fluxes in response to carbohydrate plus protein ingestion. Muscle insulin signaling was determined as well as the content and activation state of muscle microvascular eNOS.Results: High-fat overfeeding impaired postprandial glycemic control as demonstrated by higher concentrations of glucose (+11%; P = 0.004) and insulin (+19%; P = 0.035). Carbohydrate plus protein ingestion suppressed endogenous glucose production to a similar extent before and after the diet. Conversely, high-fat overfeeding reduced whole-body glucose clearance (-16%; P = 0.021) and peripheral insulin sensitivity (-26%; P = 0.006). This occurred despite only minor alterations in skeletal muscle insulin signaling. High-fat overfeeding reduced eNOS content in terminal arterioles (P = 0.017) and abolished the increase in eNOS Ser(1177) phosphorylation that was seen after carbohydrate plus protein ingestion.Conclusion: High-fat overfeeding impaired whole-body glycemic control due to reduced glucose clearance, not elevated endogenous glucose production. The finding that high-fat overfeeding abolished insulin-mediated eNOS Ser(1177) phosphorylation in the terminal arterioles suggests that impairments in the vasodilatory capacity of the skeletal muscle microvasculature may contribute to early dietary fat-induced impairments in glycemic control.

Background Call agents spend ~ 90% of their working day seated, which may negatively impact health, productivity, and wellbeing. This study aimed to explore the acceptability and feasibility of a multi-component workplace intervention targeting increased activity and decreased prolonged sitting in the contact centre setting prior to a full-scale effectiveness trial. Methods An 8-week non-randomised pre-post feasibility study was conducted. Using a mixed methods approach, focus groups and interviews were thematically analysed to explore the acceptability and feasibility of key study phases, and provide context to agents’ process evaluation and survey responses. The multi-component intervention, conducted in a single call centre, included height-adjustable workstations, emails, education and training sessions, and support from team leaders and a workplace champion. Results Six (of 20) team leaders were recruited, with 17 of 84 call agents (78% female, 39.3 ± 11.9 years) completing baseline assessments and 13 completing follow-up. High workload influenced recruitment. Call agents perceived assessments as acceptable, though strategies are needed to enhance fidelity. Education sessions, height-adjustable workstations and emails were perceived as the most effective components; however, height-adjustable hot-desks were not perceived as feasible in this setting. Conclusions This study has identified unique, pragmatic considerations for conducting a multi-level, multi-component PA and SB intervention and associated evaluation in highly sedentary call agents in the challenging contact centre setting. The intervention was largely perceived positively, with call agents and team leaders describing numerous perceived positive effects on behavioural, health and work-related outcomes. Findings will be of value to researchers attempting to intervene in contact centres and will be used by the current authors to design a subsequent trial.

Background Call agents spend ~ 90% of their working day seated, which may negatively impact health, productivity, and wellbeing. This study aimed to explore the acceptability and feasibility of a multi-component workplace intervention targeting increased activity and decreased prolonged sitting in the contact centre setting prior to a full-scale effectiveness trial. Methods An 8-week non-randomised pre-post feasibility study was conducted. Using a mixed methods approach, focus groups and interviews were thematically analysed to explore the acceptability and feasibility of key study phases, and provide context to agents’ process evaluation and survey responses. The multi-component intervention, conducted in a single call centre, included height-adjustable workstations, emails, education and training sessions, and support from team leaders and a workplace champion. Results Six (of 20) team leaders were recruited, with 17 of 84 call agents (78% female, 39.3 ± 11.9 years) completing baseline assessments and 13 completing follow-up. High workload influenced recruitment. Call agents perceived assessments as acceptable, though strategies are needed to enhance fidelity. Education sessions, height-adjustable workstations and emails were perceived as the most effective components; however, height-adjustable hot-desks were not perceived as feasible in this setting. Conclusions This study has identified unique, pragmatic considerations for conducting a multi-level, multi-component PA and SB intervention and associated evaluation in highly sedentary call agents in the challenging contact centre setting. The intervention was largely perceived positively, with call agents and team leaders describing numerous perceived positive effects on behavioural, health and work-related outcomes. Findings will be of value to researchers attempting to intervene in contact centres and will be used by the current authors to design a subsequent trial.

Contact centre call agents are highly sedentary at work, which can negatively affect cardio-metabolic health. This qualitative cross-sectional study explored factors influencing call agents’ workplace physical activity (PA) and sedentary behaviour (SB), and perspectives on strategies to help agents move more and sit less at work. Semi-structured interviews and focus groups with call agents (n = 20), team leaders (n = 11) and senior staff (n = 12) across four contact centres were guided by the socio-ecological model and analysed thematically. Agents offered insights into the impact of high occupational sitting and low PA on their physical and mental health, and factors influencing their motivation to move more and sit less at work. Team leaders, although pivotal in influencing behaviours, identified their own workload, and agents’ requirement to meet targets, as factors influencing their ability to promote agents to move more and sit less at work. Further, senior team leaders offered a broad organisational perspective on influential factors, including business needs and the importance of return on investment from PA and SB interventions. Unique factors, including continuous monitoring of productivity metrics and personal time, a physical connection to their workstation, and low autonomy over their working practices, seemed to limit call agents’ opportunity to move more and sit less at work. Proposed strategies included acknowledgement of PA and SB within policy and job roles, height-adjustable workstations, education and training sessions and greater interpersonal support. Additionally, measuring the impact of interventions was perceived to be key for developing a business case and enhancing organisational buy-in. Multi-level interventions embedded into current working practices appear important for the multiple stakeholders, while addressing concerns regarding productivity

Contact centre call agents are highly sedentary at work, which can negatively affect cardio-metabolic health. This qualitative cross-sectional study explored factors influencing call agents’ workplace physical activity (PA) and sedentary behaviour (SB), and perspectives on strategies to help agents move more and sit less at work. Semi-structured interviews and focus groups with call agents (n = 20), team leaders (n = 11) and senior staff (n = 12) across four contact centres were guided by the socio-ecological model and analysed thematically. Agents offered insights into the impact of high occupational sitting and low PA on their physical and mental health, and factors influencing their motivation to move more and sit less at work. Team leaders, although pivotal in influencing behaviours, identified their own workload, and agents’ requirement to meet targets, as factors influencing their ability to promote agents to move more and sit less at work. Further, senior team leaders offered a broad organisational perspective on influential factors, including business needs and the importance of return on investment from PA and SB interventions. Unique factors, including continuous monitoring of productivity metrics and personal time, a physical connection to their workstation, and low autonomy over their working practices, seemed to limit call agents’ opportunity to move more and sit less at work. Proposed strategies included acknowledgement of PA and SB within policy and job roles, height-adjustable workstations, education and training sessions and greater interpersonal support. Additionally, measuring the impact of interventions was perceived to be key for developing a business case and enhancing organisational buy-in. Multi-level interventions embedded into current working practices appear important for the multiple stakeholders, while addressing concerns regarding productivity

Neutrophils and monocytes are key components of the innate immune system that undergo age-associated declines in function. This study compared the impact of high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) on immune function in sedentary adults. Twenty-seven (43 ± 11 years) healthy sedentary adults were randomized into ten weeks of either a HIIT (>90% maximum heart rate) or MICT (70% maximum heart rate) group training program. Aerobic capacity (VO2peak), neutrophil and monocyte bacterial phagocytosis and oxidative burst, cell surface receptor expression, and systemic inflammation were measured before and after the training. Total exercise time commitment was 57% less for HIIT compared to that for MICT while both significantly improved VO2peak similarly. Neutrophil phagocytosis and oxidative burst and monocyte phagocytosis and percentage of monocytes producing an oxidative burst were improved by training similarly in both groups. Expression of monocyte but not neutrophil CD16, TLR2, and TLR4 was reduced by training similarly in both groups. No differences in systemic inflammation were observed for training; however, leptin was reduced in the MICT group only. With similar immune-enhancing effects for HIIT compared to those for MICT at 50% of the time commitment, our results support HIIT as a time efficient exercise option to improve neutrophil and monocyte function.

This review concludes that a sedentary lifestyle, obesity and ageing impair the vasodilator response of the muscle microvasculature to insulin, exercise and VEGF-A and reduce microvascular density. Both impairments contribute to the development of insulin resistance, obesity and chronic age-related diseases. A physically active lifestyle keeps both the vasodilator response and microvascular density high. Intravital microscopy has shown that microvascular units (MVUs) are the smallest functional elements to adjust blood flow in response to physiological signals and metabolic demands on muscle fibres. The luminal diameter of a common terminal arteriole (TA) controls blood flow through up to 20 capillaries belonging to a single MVU. Increases in plasma insulin and exercise/muscle contraction lead to recruitment of additional MVUs. Insulin also increases arteriolar vasomotion. Both mechanisms increase the endothelial surface area and therefore transendothelial transport of glucose, fatty acids (FAs) and insulin by specific transporters, present in high concentrations in the capillary endothelium. Future studies should quantify transporter concentration differences between healthy and at risk populations as they may limit nutrient supply and oxidation in muscle and impair glucose and lipid homeostasis. An important recent discovery is that VEGF-B produced by skeletal muscle controls the expression of FA transporter proteins in the capillary endothelium and thus links endothelial FA uptake to the oxidative capacity of skeletal muscle, potentially preventing lipotoxic FA accumulation, the dominant cause of insulin resistance in muscle fibres.

Key points: Skeletal muscle capillary density and vasoreactivity are reduced in obesity, due to reduced nitric oxide bioavailability. Sprint interval training (SIT) has been proposed as a time efficient alternative to moderate-intensity continuous training (MICT), but its effect on the skeletal muscle microvasculature has not been studied in obese individuals. We observed that SIT and MICT led to equal increases in capillarisation and endothelial eNOS content, while reducing endothelial NOX2 content in microvessels of young obese men. We conclude that SIT is equally effective at improving skeletal muscle capillarisation and endothelial enzyme balance, while being a time efficient alternative to traditional MICT. Sprint interval training (SIT) has been proposed as a time efficient alternative to moderate-intensity continuous training (MICT), leading to similar improvements in skeletal muscle capillary density and microvascular function in young healthy humans. In this study we made the first comparisons of the muscle microvascular response to SIT and MICT in an obese population. Sixteen young obese men (age 25 ± 1 years, BMI 34.8 ± 0.9 kg m-2) were randomly assigned to 4 weeks of MICT (40-60 min cycling at ∼65% V˙O2 peak , 5 times per week) or constant load SIT (4-7 constant workload intervals of 200% Wmax 3 times per week). Muscle biopsies were taken before and after training from the m. vastus lateralis to measure muscle microvascular endothelial eNOS content, eNOS serine1177 phosphorylation, NOX2 content and capillarisation using quantitative immunofluorescence microscopy. Maximal aerobic capacity (V˙O2 peak ), whole body insulin sensitivity and arterial stiffness were also assessed. SIT and MICT increased skeletal muscle microvascular eNOS content and eNOS ser1177 phosphorylation in terminal arterioles and capillaries (P < 0.05), but the latter effect was eliminated when normalised to eNOS content (P = 0.217). SIT and MICT also reduced microv

Using an amalgamation of previously studied "train-low" paradigms, we tested the effects of reduced carbohydrate (CHO) but high leucine availability on cell-signaling responses associated with exercise-induced regulation of mitochondrial biogenesis and muscle protein synthesis (MPS). In a repeated-measures crossover design, 11 males completed an exhaustive cycling protocol with high CHO availability before, during, and after exercise (HIGH) or alternatively, low CHO but high protein (leucine enriched) availability (LOW + LEU). Muscle glycogen was different (P < 0.05) pre-exercise (HIGH: 583 ± 158, LOW + LEU: 271 ± 85 mmol kg(-1) dw) but decreased (P < 0.05) to comparable levels at exhaustion (≈100 mmol kg(-1) dw). Despite differences (P < 0.05) in exercise capacity (HIGH: 158 ± 29, LOW + LEU: 100 ± 17 min), exercise induced (P < 0.05) comparable AMPKα2 (3-4-fold) activity, PGC-1α (13-fold), p53 (2-fold), Tfam (1.5-fold), SIRT1 (1.5-fold), Atrogin 1 (2-fold), and MuRF1 (5-fold) gene expression at 3 h post-exercise. Exhaustive exercise suppressed p70S6K activity to comparable levels immediately post-exercise (≈20 fmol min(-1) mg(-1)). Despite elevated leucine availability post-exercise, p70S6K activity remained suppressed (P < 0.05) 3 h post-exercise in LOW + LEU (28 ± 14 fmol min(-1) mg(-1)), whereas muscle glycogen resynthesis (40 mmol kg(-1) dw h(-1)) was associated with elevated (P < 0.05) p70S6K activity in HIGH (53 ± 30 fmol min(-1) mg(-1)). We conclude: (1) CHO restriction before and during exercise induces "work-efficient" mitochondrial-related cell signaling but; (2) post-exercise CHO and energy restriction

Background Within a controlled laboratory environment, high-intensity interval training (HIT) elicits similar cardiovascular and metabolic benefits as traditional moderate-intensity continuous training (MICT). It is currently unclear how HIT can be applied effectively in a real-world environment. Purpose To investigate the hypothesis that 10 weeks of HIT, performed in an instructor-led, groupbased gym setting, elicits improvements in aerobic capacity (VO2max), cardio-metabolic risk and psychological health which are comparable to MICT. Methods Ninety physically inactive volunteers (42±11 y, 27.7±4.8 kg.m-2) were randomly assigned to HIT or MICT group exercise classes. HIT consisted of repeated sprints (15-60 seconds, >90% HRmax) interspersed with periods of recovery cycling (≥25 min.session-1, 3 sessions. week-1). MICT participants performed continuous cycling (70%HRmax, 30-45 min.session-1, 5 sessions.week-1). VO2max, markers of cardio-metabolic risk, and psychological health were assessed pre and post-intervention. Results Mean weekly training time was 55±10 (HIT) and 128±44 min (MICT) (p<0.05), with greater adherence to HIT (83±14% vs. 61±15% prescribed sessions attended, respectively; p<0.05). HIT improved VO2max, insulin sensitivity, reduced abdominal fat mass, and induced favourable changes in blood lipids (p<0.05). HIT also induced beneficial effects on health perceptions, positive and negative affect, and subjective vitality (p<0.05). No difference between HIT and MICT was seen for any of these variables. Conclusions HIT performed in a real-world gym setting improves cardio-metabolic risk factors and psychological health in physically inactive adults. With a reduced time commitment and greater adherence than MICT, HIT offers a viable and effective exercise strategy to target the growing incidence of metabolic disease and psychological i

Increases in insulin‐mediated glucose uptake following endurance training (ET) and sprint interval training (SIT) have in part been attributed to concomitant increases in glucose transporter 4 (GLUT4) protein content in skeletal muscle. This study used an immunofluorescence microscopy method to investigate changes in subcellular GLUT4 distribution and content following ET and SIT. Percutaneous muscle biopsy samples were taken from the m. vastus lateralis of 16 sedentary males in the overnight fasted state before and after 6 weeks of ET and SIT. An antibody was fully validated and used to show large (> 1 μm) and smaller (<1 μm) GLUT4‐containing clusters. The large clusters likely represent trans‐Golgi network stores and the smaller clusters endosomal stores and GLUT4 storage vesicles (GSVs). Density of GLUT4 clusters was higher at the fibre periphery especially in perinuclear regions. A less dense punctate distribution was seen in the rest of the muscle fibre. Total GLUT4 fluorescence intensity increased in type I and type II fibres following both ET and SIT. Large GLUT4 clusters increased in number and size in both type I and type II fibres, while the smaller clusters increased in size. The greatest increases in GLUT4 fluorescence intensity occurred within the 1 μm layer immediately adjacent to the PM. The increase in peripheral localisation and protein content of GLUT4 following ET and SIT is likely to contribute to the improvements in glucose homeostasis observed after both training modes.