Intramuscular hematoma of the vastus lateralis following percutaneous skeletal muscle microbiopsy: a case report.

Recently, percutaneous microbiopsy needles have been used as a less invasive alternative to the Bergstrom needle for obtaining human skeletal muscle biopsy to assess changes in protein content, gene expression, and enzymatic activities. Unlike the Bergstrom muscle biopsy procedure, potential complications associated with microbiopsies of human skeletal muscle have not been documented. Therefore, the present case report follows a young male's recovery from a muscle biopsy-induced hemorrhage/hematoma of the right vastus lateralis with the specific aims of (1) informing future participants, researchers, and clinicians on expected time course of recovery and (2) informing methods to minimize future participant adverse event risk during and after the percutaneous microbiopsy procedure. The present case report demonstrates that the inadvertent hemorrhaging of a neighboring vessel by percutaneous microbiopsy procedure can be debilitating. To minimize the risk of muscle biopsy-induced hemorrhage/hematoma, we advise post-biopsy compression for up to 15 min and post-biopsy follow-up should be completed for up to 72 h. When there is indication of hematoma development, compression should be applied, and the participant should avoid exercise and physical activity.

Increasing whole-body energetic stress does not augment fasting-induced changes in human skeletal muscle.

Fasting rapidly (≤ 6 h) activates mitochondrial biogenic pathways in rodent muscle, an effect that is absent in human muscle following prolonged (10-72 h) fasting. We tested the hypotheses that fasting-induced changes in human muscle occur shortly after food withdrawal and are modulated by whole-body energetic stress. Vastus lateralis biopsies were obtained from ten healthy males before, during (4 h), and after (8 h) two supervised fasts performed with (FAST+EX) or without (FAST) 2 h of arm ergometer exercise (~ 400 kcal of added energy expenditure). PGC-1α mRNA (primary outcome measure) was non-significantly reduced (p = 0.065 [ηp2 = 0.14]) whereas PGC-1α protein decreased (main effect of time: p < 0.01) during both FAST and FAST+EX. P53 acetylation increased in both conditions (main effect of time: p < 0.01) whereas ACC and SIRT1 phosphorylation were non-significantly decreased (both p < 0.06 [ηp2 = 0.15]). Fasting-induced increases in NFE2L2 and NRF1 protein were observed (main effects of time: p < 0.03), though TFAM and COXIV protein remained unchanged (p > 0.05). Elevating whole-body energetic stress blunted the increase in p53 mRNA, which was apparent during FAST only (condition × time interaction: p = 0.04). Select autophagy/mitophagy regulators (LC3BI, LC3BII, BNIP3) were non-significantly reduced at the protein level (p ≤ 0.09 [ηp2 > 0.13]) but the LC3II:I ratio was unchanged (p > 0.05). PDK4 mRNA (p < 0.01) and intramuscular triglyceride content in type IIA fibers (p = 0.04) increased similarly during both conditions. Taken together, human skeletal muscle signaling, mRNA/protein expression, and substrate storage appear to be unaffected by whole-body energetic stress during the initial hours of fasting.

Repeatability of training-induced skeletal muscle adaptations in active young males.

OBJECTIVES: Measurements of protein content, enzymatic activity, and/or capillarization are frequently utilized as markers of skeletal muscle adaptation following exercise training. Whether changes in these markers of muscle adaptation are repeatable when individuals are repeatedly exposed to the same training stimulus is unknown. The purpose of this study was to test the repeatability of skeletal muscle adaptations to two identical training periods. METHODS: Ten active young males (age: 22 ±â€¯2 years; VO2max: 57 ±â€¯7 ml/kg/min) were exposed to two identical four-week periods of supervised high-intensity interval running (4 × 4 min at 90-95% of HRmax interspersed with 3-min at 70-75% HRmax) separated by a 3-month wash-out period. Vastus lateralis biopsies were obtained before and after each training period for the measurement of protein content, enzyme activity, and capillary density. RESULTS: Training-induced changes in citrate synthase (CS) maximal activity, protein content (PGC-1α, OXPHOS, and LDH-A), and capillary density were not repeatable within individuals (r = -0.52-0.15; ICCs: -0.42-0.04; CVs: 11-67%). Several OXPHOS complex subunits also demonstrated dissimilar group-level adaptations (period × time interaction effects, p < 0.05) with large differences (ηp2 > 0.4) between training periods. A large (ηp2 = 0.65) increase in capillary density was apparent irrespective of training period (main effect of time, p = 0.05). CONCLUSIONS: An individual (or a group of individuals) may exhibit dissimilar skeletal muscle adaptations when re-exposed to the same training stimulus. Our findings challenge the utility of classifying of individuals as high/low responders using measurements of mitochondrial protein content, CS activity and/or capillary density following a single training period.

Effect of Acute High-intensity Interval Exercise on Whole-body Fat Oxidation and Subcutaneous Adipose Tissue Cell Signaling in Overweight Women.

Exercise-induced alterations in adipose tissue insulin and/or ß-adrenergic signaling may contribute to increases in whole-body fat oxidation following acute exercise. Thus, we examined changes in insulin (Akt, AS160) and ß-adrenergic (PKA) signaling proteins in subcutaneous adipose tissue and whole-body fat oxidation in overweight women following acute high-intensity interval exercise (HIIE). Overweight females completed two experimental sessions in a randomized order: 1) control (bed rest) and 2) HIIE (10 × 4 min running intervals at 90% HRmax, 2-min recovery). Subcutaneous abdominal adipose tissue biopsies were obtained from 10 participants before (pre-), immediately (0hr) after (post-), 2hr post-, and 4hr post-exercise. Plasma glucose and insulin levels were assessed in venous blood samples obtained at each biopsy time-point from a different group of 5 participants (BMI-matched to biopsy group). Fat oxidation rates were estimated using the respiratory exchange ratio (RER) in all participants using indirect calorimetry pre-, 2hr post-, and 4hr post-exercise. RER was decreased (p < 0.05) at 2hr post-exercise after HIIE (0.77 ± 0.04) compared to control (0.84 ± 0.04). Despite higher plasma glucose (p < 0.01) and insulin (p < 0.05) levels at 0hr post-exercise versus control, no significant interaction effects were observed for Akt or AS160 phosphorylation (p > 0.05). Phosphorylation of PKA substrates was unaltered in both conditions (p > 0.05). Collectively, altered ß-adrenergic and insulin signaling in subcutaneous adnominal adipose tissue does not appear to explain increased whole-body fat oxidation following acute HIIE.

Fiber-specific and whole-muscle LRP130 expression in rested, exercised, and fasted human skeletal muscle.

Leucine-rich pentatricopeptide repeat motif-containing protein (LRP130) is implicated in the control of mitochondrial gene expression and oxidative phosphorylation in the liver, partly due to its interaction with peroxisome proliferator-activated receptor gamma co-activator 1-alpha (PGC-1α). To investigate LRP130's role in healthy human skeletal muscle, we examined LRP130's fiber-type distribution and subcellular localization (n = 6), as well as LRP130's relationship with PGC-1α protein and citrate synthase (CS) maximal activity (n = 33) in vastus lateralis samples obtained from young males. The impact of an acute bout of exercise (endurance [END] and sprint interval training [SIT]) and fasting (8 h) on LRP130 and PGC-1α expression was also determined (n = 10). LRP130 protein content paralleled fiber-specific succinate dehydrogenase activity (I > IIA) and strongly correlated with the mitochondrially localized protein apoptosis-inducing factor in type I (r = 0.75) and type IIA (r = 0.85) fibers. Whole-muscle LRP130 protein content was positively related to PGC-1α protein (r = 0.49, p < 0.01) and CS maximal activity (r = 0.42, p < 0.01). LRP130 mRNA expression was unaltered (p > 0.05) following exercise, despite ~ 6.6- and ~ 3.8-fold increases (p < 0.01) in PGC-1α mRNA expression after END and SIT, respectively. Although unchanged at the group level (p > 0.05), moderate-to-strong positive correlations were apparent between individual changes in LRP130 and PGC-1α expression at the mRNA (r = 0.63, p < 0.05) and protein (r = 0.59, p = 0.07) level in response to fasting. Our findings support a potential role for LRP130 in the maintenance of basal mitochondrial phenotype in human skeletal muscle. LRP130's importance for mitochondrial remodeling in exercised and fasted human skeletal muscle requires further investigation.

A comparison of pain responses, hemodynamic reactivity and fibre type composition between Bergström and microbiopsy skeletal muscle biopsies.

This study tested the hypotheses that 1) skeletal muscle biopsies performed with the Bergström needle evoke larger perceptions of pain and greater hemodynamic reactivity compared to biopsies performed with the microbiopsy needle, and 2) both needles yield samples with similar fibre type compositions when samples are collected at similar skeletal muscle depths. Fourteen healthy (age: 21.6 ±â€¯3.2 years; VO2peak: 41.5 ±â€¯5.8 mL/kg/min) males (n = 7) and females (n = 7) provided two resting skeletal muscle biopsies, one with each needle type, following a randomized crossover design. Participants completed the short-form McGill Pain Questionnaire and the Brief Pain Inventory before, during, and after the skeletal muscle biopsies. Hemodynamic reactivity was assessed by measuring heart rate (HR) and mean arterial pressure (MAP) at rest and during the biopsy procedures. Immunofluorescence analysis was used to assess fibre type composition in vastus lateralis samples. Compared to the microbiopsy needle, the Bergström needle elicited a larger perception of pain but similar hemodynamic reactivity during the biopsy. Both needles yielded skeletal muscle samples with similar fibre type composition and resulted in similar perceptions of pain and pain-related interference during the post-biopsy recovery period. Collectively, these findings suggest that studies should consider using the microbiopsy needle rather than the Bergström needle unless large amounts of muscle tissue or certain muscle fibre lengths are required. However, future work should determine whether our findings are generalizable to biopsies performed with different procedures and/or types of Bergström/microbiopsy needles.

The impact of acute and chronic exercise on Nrf2 expression in relation to markers of mitochondrial biogenesis in human skeletal muscle.

PURPOSE: To examine the relationship between changes in nuclear factor erythroid 2-related factor 2 (Nrf2) expression and markers of mitochondrial biogenesis in acutely and chronically exercised human skeletal muscle. METHODS: The impact of acute submaximal endurance (END) and supramaximal interval (Tabata) cycling on the upregulation of Nrf2 (and its downstream targets), nuclear respiratory factor-1 (NRF-1) and mitochondrial transcription factor A (TFAM) mRNA expression was examined in healthy young males (n = 10). The relationship between changes in citrate synthase (CS) maximal activity and the protein content of Nrf2, heme oxygenase 1 (HO-1), NRF-1, and TFAM was also investigated following 4 weeks of Tabata in a separate group of males (n = 21). RESULTS: Nrf2, NRF-1, and HO-1 mRNA expression increased after acute exercise (p < 0.05), whereas the increase in superoxide dismutase 2 (SOD2) mRNA expression approached significance (p = 0.08). Four weeks of Tabata increased CS activity and Nrf2, NRF-1, and TFAM protein content (p < 0.05), but decreased HO-1 protein content (p < 0.05). Training-induced changes in Nrf2 protein were strongly correlated with NRF-1 (r = 0.63, p < 0.01). When comparing protein content changes between individuals with the largest (HI: + 23%) and smallest (LO: - 1%) observed changes in CS activity (n = 8 each), increases in Nrf2 and TFAM protein content were apparent in the HI group only (p < 0.02) with medium-to-large effect sizes for between-group differences in changes in Nrf2 (ηp2=0.15) and TFAM (ηp2 = 0.12) protein content. CONCLUSION: Altogether, our findings support a potential role for Nrf2 in exercise-induced mitochondrial biogenesis in human skeletal muscle.

Repeatability of exercise-induced changes in mRNA expression and technical considerations for qPCR analysis in human skeletal muscle.

NEW FINDINGS: What is the central question of this study? Are individual changes in exercise-induced mRNA expression repeatable (i.e. representative of the true response to exercise rather than random error)? What is the main finding and its importance? Exercise-induced changes in mRNA expression are not repeatable even under identical experimental conditions, thereby challenging the use of mRNA expression as a biomarker of adaptive potential and/or individual responsiveness to exercise. ABSTRACT: It remains unknown if (1) the observed change in mRNA expression reflects an individual's true response to exercise or random (technical and/or biological) error, and (2) the individual responsiveness to exercise is protocol-specific. We examined the repeatability of skeletal muscle PGC-1α, PDK4, NRF-1, VEGF-A, HSP72 and p53 mRNA expression following two identical endurance exercise (END) bouts (END-1, END-2; 30 min of cycling at 65% of peak work rate (WRpeak ), n = 11) and inter-individual variability in PGC-1α and PDK4 mRNA expression following END and sprint interval training (SIT; 8 × 20 s cycling intervals at ∼170% WRpeak , n = 10) in active young males. The repeatability of key gene analysis steps (RNA extraction, reverse transcription, qPCR) and within-sample fibre-type distribution (n = 8) was also determined to examine potential sources of technical error in our analyses. Despite highly repeatable exercise bout characteristics (work rate, heart rate, blood lactate; ICC > 0.71; CV < 10%; r > 0.85, P < 0.01), gene analysis steps (ICC > 0.73; CV < 24%; r > 0.75, P < 0.01), and similar group-level changes in mRNA expression, individual changes in PGC-1α, PDK4, VEGF-A and p53 mRNA expression were not repeatable (ICC < 0.22; CV > 20%; r < 0.21). Fibre-type distribution in two portions of the same muscle biopsy was highly variable and not significantly related (ICC = 0.39; CV = 26%; r = 0.37, P = 0.37). Since individual changes in mRNA expression following identical exercise bouts were not repeatable, inferences regarding individual responsiveness to END or SIT were not made. Substantial random error exists in changes in mRNA expression following acute exercise, thereby challenging the use of mRNA expression for analysing individual responsiveness to exercise.

Contribution of central and peripheral adaptations to changes in maximal oxygen uptake following 4 weeks of sprint interval training.

The current study examined the contribution of central and peripheral adaptations to changes in maximal oxygen uptake (V̇O2max) following sprint interval training (SIT). Twenty-three males completed 4 weekly SIT sessions (8 × 20-s cycling bouts at ∼170% of work rate at V̇O2max, 10-s recovery) for 4 weeks. Following completion of training, the relationship between changes in V̇O2max and changes in central (cardiac output) and peripheral (arterial-mixed venous oxygen difference (a-vO2diff), muscle capillary density, oxidative capacity, fibre-type distribution) adaptations was determined in all participants using correlation analysis. Participants were then divided into tertiles on the basis of the magnitude of their individual V̇O2max responses, and differences in central and peripheral adaptations were examined in the top (HI; ∼10 mL·kg-1·min-1 increase in V̇O2max, p < 0.05) and bottom (LO; no change in V̇O2max, p > 0.05) tertiles (n = 8 each). Training had no impact on maximal cardiac output, and no differences were observed between the LO group and the HI group (p > 0.05). The a-vO2diff increased in the HI group only (p < 0.05) and correlated significantly (r = 0.71, p < 0.01) with changes in V̇O2max across all participants. Muscle capillary density (p < 0.02) and ß-hydroxyacyl-CoA dehydrogenase maximal activity (p < 0.05) increased in both groups, with no between-group differences (p > 0.05). Citrate synthase maximal activity (p < 0.01) and type IIA fibre composition (p < 0.05) increased in the LO group only. Collectively, although the heterogeneity in the observed V̇O2max response following 4 weeks of SIT appears to be attributable to individual differences in systemic vascular and/or muscular adaptations, the markers examined in the current study were unable to explain the divergent V̇O2max responses in the LO and HI groups.

Acute upregulation of PGC-1α mRNA correlates with training-induced increases in SDH activity in human skeletal muscle.

The purpose of the present study was to determine if acute responses in PGC-1α, VEGFA, SDHA, and GPD1-2 mRNA expression predict their associated chronic skeletal muscle molecular (SDH-GPD activity and substrate storage) and morphological (fibre-type composition and capillary density) adaptations following training. Skeletal muscle biopsies were collected from 14 recreationally active men (age: 22.0 ± 2.4 years) before (PRE) and 3 h after (3HR) the completion of an acute bout of sprint interval training (SIT) (eight 20-s intervals at ∼170% peak oxygen uptake work rate separated by 10 s of recovery). Participants then completed 6 weeks of SIT 4 times per week with additional biopsies after 2 (MID) and 6 (POST) weeks of training. Acute increases in PGC-1α mRNA strongly predicted increases in SDH activity (a marker of oxidative capacity) from PRE and MID to POST (PRE-POST: r = 0.81, r2 = 0.65, p < 0.01; MID-POST: r = 0.79, r2 = 0.62, p < 0.01) and glycogen content from MID to POST (r = 0.60, r2 = 0.36, p < 0.05). No other significant relationships were found between acute responses in PGC-1α, VEGFA, SDHA, and GPD1-2 mRNA expression and chronic adaptations to training. These results suggest that acute upregulation of PGC-1α mRNA relates to the magnitude of subsequent training-induced increases in oxidative capacity, but not other molecular and morphological chronic skeletal muscle adaptations. Additionally, acute mRNA responses in PGC-1α correlated with VEGFA, but not SDHA, suggesting a coordinated upregulation between PGC-1α and only some of its proposed targets in human skeletal muscle.

The impact of a 48-h fast on SIRT1 and GCN5 in human skeletal muscle.

The present study examined the impact of a 48 h fast on the expression and activation status of SIRT1 and GCN5, the relationship between SIRT1/GCN5 and the gene expression of PGC-1α, and the PGC-1α target PDK4 in the skeletal muscle of 10 lean healthy men (age, 22.0 ± 1.5 years; peak oxygen uptake, 47.2 ± 6.7 mL/(min·kg)). Muscle biopsies and blood samples were collected 1 h postprandial (Fed) and following 48 h of fasting (Fasted). Plasma insulin (Fed, 80.8 ± 47.9 pmol/L; Fasted, not detected) and glucose (Fed, 4.36 ± 0.86; Fasted, 3.74 ± 0.25 mmol/L, p = 0.08) decreased, confirming participant adherence to fasting. Gene expression of PGC-1α decreased (p < 0.05, -24%), while SIRT1 and PDK4 increased (p < 0.05, +11% and +1023%, respectively), and GCN5 remained unchanged. No changes were observed for whole-muscle protein expression of SIRT1, GCN5, PGC-1α, or COX IV. Phosphorylation of SIRT1, AMPKα, ACC, p38 MAPK, and PKA substrates as well as nuclear acetylation status was also unaltered. Additionally, nuclear SIRT1 activity, GCN5, and PGC-1α content remained unchanged. Preliminary findings derived from regression analysis demonstrate that changes in nuclear GCN5 and SIRT1 activity/phosphorylation may contribute to the control of PGC-1α, but not PDK4, messenger RNA expression following fasting. Collectively, and in contrast with previous animal studies, our data are inconsistent with the altered activation status of SIRT1 and GCN5 in response to 48 h of fasting in human skeletal muscle.

SIRT3 gene expression but not SIRT3 subcellular localization is altered in response to fasting and exercise in human skeletal muscle.

NEW FINDINGS: What is the central question of this study? Evidence from cellular and animal models suggests that SIRT3 is involved in regulating aerobic ATP production. Thus, we investigated whether changes in fatty acid and oxidative metabolism known to accompany fasting and exercise occur in association with changes in SIRT3 mitochondrial localization and expression in human skeletal muscle. What is the main finding and its importance? We find that 48 h of fasting and acute endurance exercise decrease SIRT3 mRNA expression but do not alter SIRT3 mitochondrial localization despite marked increases in fatty acid oxidation. This suggests that SIRT3 activity is not regulated by changes in mitochondrial localization in response to cellular energy stress in human skeletal muscle. The present study examined SIRT3 expression and SIRT3 mitochondrial localization in response to acute exercise and short-term fasting in human skeletal muscle. Experiment 1 involved eight healthy men (age, 21.4 ± 2.8 years; peak O2 uptake, 47.1 ± 11.8 ml min(-1)  kg(-1) ) who performed a single bout of exercise at ∼55% of peak aerobic work rate for 1 h. Muscle biopsies were obtained at rest (Rest), immediately after exercise (EX-0) and 3 h postexercise (EX-3). Experiment 2 involved 10 healthy men (age, 22.0 ± 1.5 years; peak O2 uptake, 46.9 ± 6.0 ml min−1 kg−1) who underwent a 48 h fast, with muscle biopsies collected 1 h postprandial (Fed) and after 48 h of fasting (Fast). Mitochondrial respiration was measured using high-resolution respirometry in permeabilized muscle fibre bundles to assess substrate oxidation. Whole body fat oxidation increased after both exercise (Rest, 0.96 ± 0.32 kcal min(-1) ; Exercise, 5.66 ± 1.97 kcal min(-1) ; P < 0.001) and fasting (Fed, 0.87 ± 0.51 kcal min(-1) ; Fast, 1.30 ± 0.37 kcal min(-1) , P < 0.05). SIRT3 gene expression decreased (P < 0.05) after both exercise (-8%) and fasting (-19%); however, SIRT3 whole muscle protein content was unaltered after fasting. No changes were observed in SIRT3 mitochondrial localization following either exercise or fasting. Fasting also decreased the Vmax of glutamate [80 ± 43 versus 50 ± 21 pmol s(-1)  (mg dry weight)(-1) ; P < 0.05]. These findings suggest that SIRT3 does not appear to be regulated by changes in mitochondrial localization at the time points measured in the present study in response to cellular energy stress in human skeletal muscle.

Resveratrol supplementation does not augment performance adaptations or fibre-type-specific responses to high-intensity interval training in humans.

The present study examined the effect of concurrent exercise training and daily resveratrol (RSV) supplementation (150 mg) on training-induced adaptations following low-dose high-intensity interval training (HIIT). Sixteen recreationally active (∼22 years, ∼51 mL·kg(-1)·min(-1)) men were randomly assigned in a double-blind fashion to either the RSV or placebo group with both groups performing 4 weeks of HIIT 3 days per week. Before and after training, participants had a resting muscle biopsy taken, completed a peak oxygen uptake test, a Wingate test, and a submaximal exercise test. A main effect of training (p < 0.05) and interaction effect (p < 0.05) on peak aerobic power was observed; post hoc pairwise comparisons revealed that a significant (p < 0.05) increase occurred in the placebo group only. Main effects of training (p < 0.05) were observed for both peak oxygen uptake (placebo - pretraining: 51.3 ± 1.8, post-training: 54.5 ± 1.5 mL·kg(-1)·min(-1), effect size (ES) = 0.93; RSV - pretraining: 49.6 ± 2.2, post-training: 52.3 ± 2.5 mL·kg(-1)·min(-1), ES = 0.50) and Wingate peak power (placebo: pretraining: 747 ± 39, post-training: 809 ± 31 W, ES = 0.84; RSV - pretraining: 679 ± 39, post-training: 691 ± 43 W, ES = 0.12). Fibre-type distribution was unchanged, while a main effect of training (p < 0.05) was observed for succinate dehydrogenase activity and glycogen content, but not α-glycerophosphate dehydrogenase activity or intramuscular lipids in type I and IIA fibres. The fold change in PGC-1α, SIRT1, and SOD2 gene expression following training was significantly (p < 0.05) lower in the RSV group than placebo. These results suggest that concurrent exercise training and RSV supplementation may alter the normal training response induced by low-volume HIIT.

An examination of resveratrol's mechanisms of action in human tissue: impact of a single dose in vivo and dose responses in skeletal muscle ex vivo.

The current study tested the hypothesis that a single, moderate dose of RSV would activate the AMPK/SIRT1 axis in human skeletal muscle and adipose tissue. Additionally, the effects of RSV on mitochondrial respiration in PmFBs were examined. Eight sedentary men (23.8±2.4 yrs; BMI: 32.7±7.1) reported to the lab on two occasions where they were provided a meal supplemented with 300 mg of RSV or a placebo. Blood samples, and a muscle biopsy were obtained in the fasted state and again, with the addition of an adipose tissue biopsy, two hours post-prandial. The effect of RSV on mitochondrial respiration was examined in PmFBs taken from muscle biopsies from an additional eight men (23.4±5.4 yrs; BMI: 24.4±2.8). No effect of RSV was observed on nuclear SIRT1 activity, acetylation of p53, or phosphorylation of AMPK, ACC or PKA in either skeletal muscle or adipose tissue. A decrease in post absorptive insulin levels was accompanied by elevated skeletal muscle phosphorylation of p38 MAPK, but no change in either skeletal muscle or adipose tissue insulin signalling. Mitochondrial respiration in PmFBs was rapidly inhibited by RSV at 100-300 uM depending on the substrate examined. These results question the efficacy of a single dose of RSV at altering skeletal muscle and adipose tissue AMPK/SIRT1 activity in humans and suggest that RSV mechanisms of action in humans may be associated with altered cellular energetics resulting from impaired mitochondrial ATP production.

Dissociation of increases in PGC-1α and its regulators from exercise intensity and muscle activation following acute exercise.

Muscle activation as well as changes in peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α) following high-intensity interval exercise (HIIE) were examined in young healthy men (n  = 8; age, 21.9±2.2 yrs; VO2peak, 53.1±6.4 ml/min/kg; peak work rate, 317±23.5 watts). On each of 3 visits HIIE was performed on a cycle ergometer at a target intensity of 73, 100, or 133% of peak work rate. Muscle biopsies were taken at rest and three hours after each exercise condition. Total work was not different between conditions (∼730 kJ) while average power output (73%, 237±21; 100%, 323±26; 133%, 384±35 watts) and EMG derived muscle activation (73%, 1262±605; 100%, 2089±737; 133%, 3029±1206 total integrated EMG per interval) increased in an intensity dependent fashion. PGC-1α mRNA was elevated after all three conditions (p<0.05), with a greater increase observed following the 100% condition (∼9 fold, p<0.05) compared to both the 73 and 133% conditions (∼4 fold). When expressed relative to muscle activation, the increase in PGC-1α mRNA for the 133% condition was less than that for the 73 and 100% conditions (p<0.05). SIRT1 mRNA was also elevated after all three conditions (∼1.4 fold, p<0.05), with no difference between conditions. These findings suggest that intensity-dependent increases in PGC-1α mRNA following submaximal exercise are largely due to increases in muscle recruitment. As well, the blunted response of PGC-1α mRNA expression following supramaximal exercise may indicate that signalling mediated activation of PGC-1α may also be blunted. We also indentify that increases in PDK4, SIRT1, and RIP140 mRNA following acute exercise are dissociated from exercise intensity and muscle activation, while increases in EGR1 are augmented with supramaximal HIIE (p<0.05).

Reducing the intensity and volume of interval training diminishes cardiovascular adaptation but not mitochondrial biogenesis in overweight/obese men.

OBJECTIVE: The purpose of this research was to determine if the adaptations to high intensity interval training (HIT) are mitigated when both intensity and training volume (i.e. exercise energy expenditure) are reduced. METHODS: 19 overweight/obese, sedentary males (Age: 22.7±3.9 yrs, Body Mass Index: 31.4±2.6 kg/m(2), Waist Circumference: 106.5±6.6 cm) performed 9 sessions of interval training using a 1-min on, 1-min off protocol on a cycle ergometer over three weeks at either 70% (LO) or 100% (HI) peak work rate. RESULTS: Cytochrome oxidase I protein content, cytochrome oxidase IV protein content, and citrate synthase maximal activity all demonstrated similar increases between groups with a significant effect of training for each. ß-hydroxyacyl-CoA dehydrogenase maximal activity tended to increase with training but did not reach statistical significance (p = 0.07). Peroxisome proliferator-activated receptor gamma coactivator-1α and silent mating type information regulator 2 homolog 1 protein contents also increased significantly (p = 0.047), while AMP-activated protein kinase protein content decreased following the intervention (p = 0.019). VO2peak increased by 11.0±7.4% and 27.7±4.4% in the LO and HI groups respectively with significant effects of both training (p<0.001) and interaction (p = 0.027). Exercise performance improved by 8.6±7.6% in the LO group and 14.1±4.3% in the HI group with a significant effect of training and a significant difference in the improvement between groups. There were no differences in perceived enjoyment or self-efficacy between groups despite significantly lower affect scores during training in the HI group. CONCLUSIONS: While improvements in aerobic capacity and exercise performance were different between groups, changes in oxidative capacity were similar despite reductions in both training intensity and volume.