Effect of high-frequency resistance exercise on adaptive responses in skeletal muscle

PURPOSE: Regulation of skeletal muscle mass is highly dependent on contractile loading. The purpose of this study was to examine changes in growth factor and inflammatory pathways following high-frequency resistance training. METHODS: Using a novel design in which male Sprague-Dawley rats undertook a "stacked" resistance training protocol designed to generate a summation of transient exercise-induced signaling responses (four bouts of three sets × 10 repetitions of squat exercise, separated by 3 h of recovery), we determined the effects of high training frequency on signaling pathways and transcriptional activity regulating muscle mass. RESULTS: The stacked training regimen resulted in acute suppression of insulin-like growth factor 1 mRNA abundance (P < 0.05) and Akt phosphorylation (P < 0.05), an effect that persisted 48 h after the final training bout. Conversely, stacked training elicited a coordinated increase in the expression of tumor necrosis factor alpha, inhibitor kappa B kinase alpha/beta activity (P < 0.05), and p38 mitogen-activated protein kinase phosphorylation (P < 0.05) at 3 h after each training bout. In addition, the stacked series of resistance exercise bouts induced an increase in p70 S6 kinase phosphorylation 3 h after bouts ×3 and ×4, independent of the phosphorylation state of Akt. CONCLUSIONS: Our results indicate that high resistance training frequency extends the transient activation of inflammatory signaling cascades, concomitant with persistent suppression of key mediators of anabolic responses. We provide novel insights into the effects of the timing of exercise-induced overload and recovery on signal transduction pathways and transcriptional activity regulating skeletal muscle mass in vivo.

Acute inflammatory response to low-, moderate- and high-load resistance exercise in women with breast cancer-related lymphoedema

Background Resistance exercise is emerging as a potential adjunct therapy to aid in the management of breast cancer-related lymphedema (BCRL). However, the mechanisms underlying the relationships between the acute and long-term benefits of resistance exercise on BCRL are not well understood. Purpose. To examine the acute inflammatory response to upper-body resistance exercise in women with BCRL and to compare these effects between resistance exercises involving low-, moderate- and high-loads. The impact on lymphoedema status and associated symptoms was also compared. Methods Twenty-one women aged 62 ± 10 years with mild to severe BCRL participated in the study. Participants completed a low-load (15-20 repetition maximum), moderate-load (10-12 repetition maximum) and high-load (6-8 repetition maximum) exercise sessions consisting of three sets of six upper-body resistance exercises. Sessions were completed in a randomized order separated by a seven to 10 day wash-out period. Venous blood samples were obtained to assess markers of exercise-induced muscle damage and inflammation (creatine kinase [CK], C-reactive protein [CRP], interleukin-6 [IL-6] and tumour necrosis factor-alpha [TNF-α]). Lymphoedema status was assessed using bioimpedance spectroscopy and arm circumferences, and associated symptoms were assessed using visual analogue scales (VAS) for pain, heaviness and tightness. Measurements were conducted before and 24 hours after the exercise sessions. Results No significant changes in CK, CRP, IL-6 and TNF-α were observed following the low-, moderate- or high-load resistance exercise sessions. There were no significant changes in arm swelling or symptom severity scores across the three resistance exercise conditions. Conclusions The magnitude of acute exercise-induced inflammation following upper-body resistance exercise in women with BCRL does not vary between resistance exercise loads. Given these observations, moderate- to high-load resistance training is recommended for this patient population as these loads prompt superior physiological and functional benefits.

The effects of high-intensity resistance exercise on the blood lipid profile and liver function in hypercholesterolemic hamsters

It is well established that atherogenic dyslipidemia, characterized by high levels of triglycerides (TG), total cholesterol (TC), and low-density lipoprotein (LDL) cholesterol and low levels of high-density lipoprotein (HDL) cholesterol, constitutes important risk factors for cardiovascular disease. Regular exercise has been associated with a reduced risk for metabolic diseases. However, studies supporting the concept that resistance exercise is a modifier of blood lipid parameters are often contradictory. The aim of this study was to investigate the effects of high-intensity resistance exercise on the serum levels of TG, TC, HDL and non-HDL cholesterol, glucose, and the liver function enzymes alanine aminotransferase (ALT, EC 2.6.1.2) and aspartate aminotransferase (AST, EC 2.6.1.1) in golden Syrian hamsters (Mesocricetus auratus (Waterhouse, 1839)) fed a hypercholesterolemic diet. Sedentary groups (S) and exercise groups (E) were fed a standard diet (SS and ES) or a cholesterol-enriched diet (standard plus 1% cholesterol, SC and EC). Resistance exercise was performed by jumps in the water, carrying a load strapped to the chest, representing 10 maximum repetitions (10 RM, 30 s rest, five days per week for five weeks). Mean blood sample comparisons were made by ANOVA + Tukey or ANOVA + Kruskal-Wallis tests (p < 0.05) to compare parametric and nonparametric samples, respectively. There were no differences in blood lipids between the standard diet groups (SS and ES) (p > 0.05). However, the EC group increased the glucose, non-HDL, and TC levels in comparison with the ES group. Moreover, the EC group increased the TG levels versus the SC group (p < 0.05). In addition, the ALT levels were increased only by diet treatment. These findings indicated that high-intensity resistance exercise contributed to dyslipidemia in hamsters fed a hypercholesterolemic diet, whereas liver function enzymes did not differ in regards to the exercise protocol.

Determination of metabolic equivalents during low-and high-intensity resistance exercise in healthy young subjects and patients with type 2 diabetes

The purpose of this study was to quantify the metabolic equivalents (METs) of resistance exercise in obese patients with type 2 diabetes (T2DM) and healthy young subjects and to evaluate whether there were differences between sessions executed at low- versus high-intensity resistance exercise. Twenty obese patients with T2DM (62.9±6.1 years) and 22 young subjects (22.6±1.9 years) performed two training sessions: one at vigorous intensity (80% of 1-repetition maximum (1RM)) and one at moderate intensity (60% of 1RM). Both groups carried out three strength exercises with a 2-day recovery between sessions. Oxygen consumption was continuously measured 15 min before, during and after each training session. Obese T2DM patients showed lower METs values compared with young healthy participants at the baseline phase (F= 2043.86; P<0.01), during training (F=1140.59; P<0.01) and in the post-exercise phase (F=1012.71; P<0.01). No effects were detected in the group x intensity analysis of covariance. In this study, at both light-moderate and vigorous resistance exercise intensities, the METs value that best represented both sessions was 3 METs for the obese elderly T2DM patients and 5 METs for young subjects.

Changes in neutrophil surface receptor expression, degranulation, and respiratory burst activity after moderate- and high-intensity exercise

Intense exercise stimulates the systemic release of a variety of factors that alter neutrophil surface receptor expression and functional activity. These alterations may influence resistance to infection after intense exercise. The aim of this study was to examine the influence of exercise intensity on neutrophil receptor expression, degranulation (measured by plasma and intracellular myeloperoxidase concentrations), and respiratory burst activity. Ten well-trained male runners ran on a treadmill for 60 min at 60% [moderate-intensity exercise (MI)] and 85% maximal oxygen consumption [high-intensity exercise (HI)]. Blood was drawn immediately before and after exercise and at 1 h postexercise. Immediately after HI, the expression of the neutrophil receptor CD16 was significantly below preexercise values (P < 0.01), whereas MI significantly reduced CD35 expression below preexercise values (P < 0.05). One hour after exercise at both intensities, there was a significant decline in CD11b expression (P < 0.05) and a further decrease in CD16 expression compared with preexercise values (P < 0.01). CD16 expression was lower 1 h after HI than 1 h after MI (P < 0.01). Immediately after HI, intracellular myeloperoxidase concentration was less than preexercise values (P < 0.01), whereas plasma myeloperoxidase concentration was greater (P < 0.01), indicating that HI stimulated neutrophil degranulation. Plasma myeloperoxidase concentration was higher immediately after HI than after MI (P < 0.01). Neutrophil respiratory burst activity increased after HI (P < 0.01). In summary, both MI and HI reduced neutrophil surface receptor expression. Although CD16 expression was reduced to a greater extent after HI, this reduction did not impair neutrophil degranulation and respiratory burst activity.

Low muscle glycogen concentration does not suppress the anabolic response to resistance exercise

We determined the effect of muscle glycogen concentration and postexercise nutrition on anabolic signaling and rates of myofibrillar protein synthesis after resistance exercise (REX). Sixteen young, healthy men matched for age, body mass, peak oxygen uptake (VO2peak) and strength (one repetition maximum; 1RM) were randomly assigned to either a nutrient or placebo group. After 48 h diet and exercise control, subjects undertook a glycogen-depletion protocol consisting of one-leg cycling to fatigue (LOW), whereas the other leg rested (NORM). The next morning following an overnight fast, a primed, constant infusion of L-[ring-13C6] phenylalanine was commenced and subjects completed 8 sets of 5 unilateral leg press repetitions at 80% 1RM. Immediately after REX and 2 h later, subjects consumed a 500 ml bolus of a protein/CHO (20 g whey + 40 g maltodextrin) or placebo beverage. Muscle biopsies from the vastus lateralis of both legs were taken at rest and 1 and 4 h after REX. Muscle glycogen concentration was higher in the NORM than LOW at all time points in both nutrient and placebo groups (P < 0.05). Postexercise Akt-p70S6K-rpS6 phosphorylation increased in both groups with no differences between legs (P < 0.05). mTORSer2448 phosphorylation in placebo increased 1 h after exercise in NORM (P < 0.05), whereas mTOR increased ?4-fold in LOW (P < 0.01) and ?11 fold in NORM with nutrient (P < 0.01; different between legs P < 0.05). Post-exercise rates of MPS were not different between NORM and LOW in nutrient (0.070 ± 0.022 vs. 0.068 ± 0.018 %/h) or placebo (0.045 ± 0.021 vs. 0.049 ± 0.017 %/h). We conclude that commencing high-intensity REX with low muscle glycogen availability does not compromise the anabolic signal and subsequent rates of MPS, at least during the early (4 h) postexercise recovery period.

Sex-based comparisons of myofibrillar protein synthesis after resistance exercise in the fed state

Sex-based comparisons of myofibrillar protein synthesis after resistance exercise in the fed state. J Appl Physiol 112: 1805-1813, 2012. First published March 1, 2012; doi:10.1152/japplphysiol.00170.2012.- We made sex-based comparisons of rates of myofibrillar protein synthesis (MPS) and anabolic signaling after a single bout of high-intensity resistance exercise. Eight men (20 ± 10 yr, BMI = 24.3 ± 2.4) and eight women (22 ± 1.8 yr, BMI = 23.0 ± 1.9) underwent primed constant infusions of L-[ring-13C6]phenylalanine on consecutive days with serial muscle biopsies. Biopsies were taken from the vastus lateralis at rest and 1, 3, 5, 24, 26, and 28 h after exercise. Twenty-five grams of whey protein was ingested immediately and 26 h after exercise. We also measured exercise-induced serum testosterone because it is purported to contribute to increases in myofibrillar protein synthesis (MPS) postexercise and its absence has been hypothesized to attenuate adaptative responses to resistance exercise in women. The exercise-induced area under the testosterone curve was 45-fold greater in men than women in the early (1 h) recovery period following exercise (P < 0.001). MPS was elevated similarly in men and women (2.3- and 2.7-fold, respectively) 1-5 h postexercise and after protein ingestion following 24 h recovery. Phosphorylation of mTORSer2448 was elevated to a greater extent in men than women acutely after exercise (P = 0.003), whereas increased phosphorylation of p70S6K1Thr389 was not different between sexes. Androgen receptor content was greater in men (main effect for sex, P = 0.049). Atrogin-1 mRNA abundance was decreased after 5 h recovery in both men and women (P < 0.001), and MuRF-1 expression was elevated in men after protein ingestion following 24 h recovery (P = 0.003). These results demonstrate minor sex-based differences in signaling responses and no difference in the MPS response to resistance exercise in the fed state. Interestingly, our data demonstrate that exerciseinduced increases in MPS are dissociated from postexercise testosteronemia and that stimulation of MPS occurs effectively with low systemic testosterone concentrations in women.

Early time course of Akt phosphorylation after endurance and resistance exercise

Purpose The aim of this study was to determine the early time course of exercise-induced signaling after divergent contractile activity associated with resistance and endurance exercise. Methods Sixteen male subjects were randomly assigned to either a cycling (CYC; n = 8, 60 min, 70% V?O2peak) or resistance (REX; n = 8, 8×5 leg extension, 80% one-repetition maximum, 3-min recovery) exercise group. Serial muscle biopsies were obtained from vastus lateralis at rest before, immediately after, and after 15, 30, and 60 min of passive recovery to determine early signaling responses after exercise. Results There were comparable increases from rest in AktThr308/Ser473 and mTORSer2448 phosphorylation during the postexercise time course that peaked 30-60 min after both CYC and REX (P<0.05). There were also similar patterns in p70S6K Thr389 and 4E-BP1Thr37/46 phosphorylation, but a greater magnitude of effect was observed for REX and CYC, respectively (P<0.05). However, AMPKThr172 phosphorylation was only significantly elevated after CYC (P<0.05), and we observed divergent responses for glycogen synthaseSer641 and AS160 phosphorylation that were enhanced after CYC but not REX (P<0.05). Conclusions We show a similar time course for Akt-mTOR-S6K phosphorylation during the initial 60-min recovery period after divergent contractile stimuli. Conversely, enhanced phosphorylation status of proteins that promote glucose transport and glycogen synthesis only occurred after endurance exercise. Our results indicate that endurance and resistance exercise initiate translational signaling, but high-load, low-repetition contractile activity failed to promote phosphorylation of pathways regulating glucose metabolism.

Cold water immersion enhances recovery of submaximal muscle function after resistance exercise

We investigated the effect of cold water immersion (CWI) on the recovery of muscle function and physiological responses following high-intensity resistance exercise. Using a randomized, cross-over design, 10 physically active men performed high-intensity resistance exercise, followed by one of two recovery interventions: 10 min of cold water immersion at 10°C, or 10 min active recovery (low-intensity cycling). After the recovery interventions, maximal muscle function was assessed after 2 h and 4 h by measuring jump height and isometric squat strength. Submaximal muscle function was assessed after 6 h by measuring the average load lifted during six sets of 10 squats at 80% 1RM. Intramuscular temperature (1 cm) was also recorded, and venous blood samples were analyzed for markers of metabolism, vasoconstriction and muscle damage. CWI did not enhance recovery of maximal muscle function. However, during the final three sets of the submaximal muscle function test, the participants lifted a greater load (p<0.05; 38%; Cohen’s d 1.3) following CWI compared with active recovery. During CWI, muscle temperature decreased 6°C below post-exercise values, and remained below pre-exercise values for another 35 min. Venous blood O2 saturation decreased below pre-exercise values for 1.5 h after CWI. Serum endothelin-1 concentration did not change after CWI, whereas it decreased after active recovery. Plasma myoglobin concentration was lower, whereas plasma interleukin-6 concentration was higher after CWI compared with active recovery. These results suggest that cold water immersion after resistance exercise allow athletes to complete more work during subsequent training sessions, which could enhance long-term training adaptations.

Effects of cold water immersion and active recovery on hemodynamics and recovery of muscle strength following resistance exercise

Cold water immersion (CWI) and active recovery (ACT) are frequently used as post-exercise recovery strategies. However, the physiological effects of CWI and ACT after resistance exercise are not well characterized. We examined the effects of CWI and ACT on cardiac output (Q), muscle oxygenation (SmO2) and blood volume (tHb), muscle temperature (Tmuscle ) and isometric strength after resistance exercise. On separate days, 10 men performed resistance exercise, followed by 10 min CWI at 10°C or 10 min ACT (low-intensity cycling). Q (7.9±2.7 l) and Tmuscle (2.2±0.8ºC) increased, whereas SmO2 (-21.5±8.8%) and tHb (-10.1±7.7 μM) decreased after exercise (p<0.05). During CWI, Q ̇(-1.1±0.7 l) and Tmuscle (-6.6±5.3ºC) decreased, while tHb (121±77 μM) increased (p<0.05). In the hour after CWI, Q ̇and Tmuscle remained low, while tHb also decreased (p<0.05). By contrast, during ACT, Q ̇(3.9±2.3 l), Tmuscle (2.2±0.5ºC), SmO2 (17.1±5.7%) and tHb (91±66 μM) all increased (p<0.05). In the hour after ACT, Tmuscle and tHb remained high (p<0.05). Peak isometric strength during 10 s maximum voluntary contractions (MVCs) did not change significantly after CWI, whereas it decreased after ACT (-30 to -45 Nm; p<0.05). Muscle deoxygenation time during MVCs increased after ACT (p<0.05), but not after CWI. Muscle reoxygenation time after MVCs tended to increase after CWI (p=0.052). These findings suggest firstly that hemodynamics and muscle temperature after resistance exercise are dependent on ambient temperature and metabolic demands with skeletal muscle, and secondly, that recovery of strength after resistance exercise is independent of changes in hemodynamics and muscle temperature.

Impact of resistance exercise on ribosome biogenesis is acutely regulated by post-exercise recovery strategies

Muscle hypertrophy occurs following increased protein synthesis, which requires activation of the ribosomal complex. Additionally, increased translational capacity via elevated ribosomal RNA (rRNA) synthesis has also been implicated in resistance training-induced skeletal muscle hypertrophy. The time course of ribosome biogenesis following resistance exercise (RE) and the impact exerted by differing recovery strategies remains unknown. In the present study, the activation of transcriptional regulators, the expression levels of pre-rRNA, and mature rRNA components were measured through 48 h after a single-bout RE. In addition, the effects of either low-intensity cycling (active recovery, ACT) or a cold-water immersion (CWI) recovery strategy were compared. Nine male subjects performed two bouts of high-load RE randomized to be followed by 10 min of either ACT or CWI. Muscle biopsies were collected before RE and at 2, 24, and 48 h after RE. RE increased the phosphorylation of the p38-MNK1-eIF4E axis, an effect only evident with ACT recovery. Downstream, cyclin D1 protein, total eIF4E, upstream binding factor 1 (UBF1), and c-Myc proteins were all increased only after RE with ACT. This corresponded with elevated abundance of the pre-rRNAs (45S, ITS-28S, ITS-5.8S, and ETS-18S) from 24 h after RE with ACT. In conclusion, coordinated upstream signaling and activation of transcriptional factors stimulated pre-rRNA expression after RE. CWI, as a recovery strategy, markedly blunted these events, suggesting that suppressed ribosome biogenesis may be one factor contributing to the impaired hypertrophic response observed when CWI is used regularly after exercise.

mVps34 is activated following high-resistance contractions

Following resistance exercise in the fasted state, both protein synthesis and degradation in skeletal muscle are increased. The addition of essential amino acids potentiates the synthetic response suggesting that an amino acid sensor, which is involved in both synthesis and degradation, may be activated by resistance exercise. One such candidate protein is the class 3 phosphatidylinositol 3OH-kinase (PI3K) Vps34. To determine whether mammalian Vps34 (mVps34) is modulated by high-resistance contractions, mVps34 and S6K1 (an index of mTORC1) activity were measured in the distal hindlimb muscles of rats 0.5, 3, 6 and 18 h after acute unilateral high-resistance contractions with the contralateral muscles serving as a control. In the lengthening tibialis anterior (TA) muscle, S6K1 (0.5 h = 366.3 +/- 112.08%, 3 h = 124.7 +/- 15.96% and 6 h = 129.2 +/- 0%) and mVps34 (3 h = 68.8 +/- 15.1% and 6 h = 36.0 +/- 8.79%) activity both increased, whereas in the shortening soleus and plantaris (PLN) muscles the increase was significantly lower (PLN S6K1 0.5 h = 33.1 +/- 2.29% and 3 h = 47.0 +/- 6.65%; mVps34 3 h = 24.5 +/- 7.92%). HPLC analysis of the TA demonstrated a 25% increase in intramuscular leucine concentration in rats 1.5 h after exercise. A similar level of leucine added to C2C12 cells in vitro increased mVps34 activity 3.2-fold. These data suggest that, following high-resistance contractions, mVps34 activity is stimulated by an influx of essential amino acids such as leucine and this may prolong mTORC1 signalling and contribute to muscle hypertrophy.

High intensity exercise training worsens alveolar destruction in pulmonary emphysema rats

OBJECTIVE: Investigation of standard intensities of physical exercise is important to better comprehend and develop rehabilitation programs for emphysema. We aimed to evaluate the effects of different intensities (moderate and high-intensity) of physical exercise on the development of a protease-induced (papain intratracheal instillation) emphysema in rats. METHODS: Male Wistar rats were randomly separated into five groups that received intratracheal instillation of papain solution or vehicle: (i) papain high intensity exercise, (ii) papain moderate exercise, (iii) saline high intensity exercise, (iv) saline sedentary and (v) papain sedentary. Forty days after intratracheal instillation, the exercise groups were submitted to an exercise-training protocol on a treadmill during 10 weeks, 5 days/week, at 0.9 km/h (Papain and saline high exercise), or at 0.6 km/h (papain moderate exercise).We measured respiratory system elastance and resistance, the collagen fiber lung parenchyma, and the pulmonary mean linear intercept. RESULTS: All animal groups that received papain instillation presented higher alveolar wall destruction compared to animals that received only saline solution. The papain high intensity exercise group presented higher values of mean linear intercept compared to emphysema groups that were trained at a moderate intensity or not submitted to exercise. CONCLUSION: High intensity exercise training worsened alveolar destruction in an experimental model of emphysema in rats when compared to moderate intensity exercise, or to no exercise.

Analysis of autonomic modulation after an acute session of resistance exercise at different intensities in chronic obstructive pulmonary disease patients

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Influence of different resistance exercise loading schemes on mechanical power output in work to rest ratio - equated and - nonequated conditions

Paulo CA, Roschel H, Ugrinowitsch C, Kobal R and Tricoli V. Influence of different resistance exercise loading schemes on mechanical power output in work to rest ratio-equated and -nonequated conditions. J Strength Cond Res 26(5): 1308-1312, 2012-It is well known that most sports are characterized by the performance of intermittent high-intensity actions, requiring high muscle power production within different intervals. In fact, the manipulation of the exercise to rest ratio in muscle power training programs may constitute an interesting strategy when considering the specific performance demand of a given sport modality. Thus, the aim of this study was to evaluate the influence of different schemes of rest intervals and number of repetitions per set on muscle power production in the squat exercise between exercise to rest ratio-equated and -nonequated conditions. Nineteen young males (age: 25.7 +/- 4.4 years; weight: 81.3 +/- 13.7 kg; height: 178.1 +/- 5.5 cm) were randomly submitted to 3 different resistance exercise loading schemes, as follows: short-set short-interval condition (SSSI; 12 sets of 3 repetitions with a 27.3-second interval between sets); short-set long-interval condition (SSLI; 12 sets of 3 repetitions with a 60-second interval between sets); long-set long-interval (LSLI; 6 sets of 6 repetitions with a 60-second rest interval between sets). The main finding of the present study is that the lower exercise to rest ratio protocol (SSLI) resulted in greater average power production (601.88 +/- 142.48 W) when compared with both SSSI and LSLI (581.86 +/- 113.18 W; 578 +/- 138.78 W, respectively). Additionally, both the exercise to rest ratio-equated conditions presented similar performance and metabolic results. In summary, these findings suggest that shorter rest intervals may fully restore the individual's ability to produce muscle power if a smaller exercise volume per set is performed and that lower exercise to rest ratio protocols result in greater average power production when compared with higher ratio ones.