Time course of molecular responses of human skeletal muscle to acute bouts of resistance exercise.

Resistance exercise (RE) training, designed to induce hypertrophy, strives for optimal activation of anabolic and myogenic mechanisms to increase myofiber size. Clearly, activation of these mechanisms must precede skeletal muscle growth. Most mechanistic studies of RE have involved analysis of outcome variables after many training sessions. This study measured molecular level responses to RE on a scale of hours to establish a time course for the activation of myogenic mechanisms. Muscle biopsy samples were collected from nine subjects before and after acute bouts of RE. The response to a single bout was assessed at 12 and 24 h postexercise. Further samples were obtained 24 and 72 h after a second exercise bout. RE was induced by neuromuscular electrical stimulation to generate maximal isometric contractions in the muscle of interest. A single RE bout resulted in increased levels of mRNA for IGF binding protein-4 (84%), MyoD (83%), myogenin (approximately 3-fold), cyclin D1 (50%), and p21-Waf1 (16-fold), and a transient decrease in IGF-I mRNA (46%). A temporally conserved, significant correlation between myogenin and p21 mRNA was observed (r = 0.70, P < or = 0.02). The mRNAs for mechano-growth factor, IGF binding protein-5, and the IGF-I receptor were unchanged by RE. Total skeletal muscle RNA was increased 72 h after the second serial bout of RE. These results indicate that molecular adaptations of skeletal muscle to loading respond in a very short time. This approach should provide insights on the mechanisms that modulate adaptation to RE and may be useful in evaluating RE training protocol variables with high temporal resolution.     

Serum leptin responses after acute resistance exercise protocols.

This study examined the acute effects of maximum strength (MS), muscular hypertrophy (MH), and strength endurance (SE) resistance exercise protocols on serum leptin. Ten young lean men (age = 23 +/- 4 yr; body weight = 79.6 +/- 5.2 kg; body fat = 10.2 +/- 3.9%) participated in MS [4 sets x 5 repetitions (reps) at 88% of 1 repetition maximum (1 RM) with 3 min of rest between sets], MH (4 sets x 10 reps at 75% of 1 RM with 2 min of rest between sets), SE (4 sets x 15 reps at 60% of 1 RM with 1 min of rest between sets), and control (C) sessions. Blood samples were collected before and immediately after exercise and after 30 min of recovery. Serum leptin at 30 min of recovery exhibited similar reductions from baseline after the MS (-20 +/- 5%), MH (-20 +/- 4%), and SE (-15 +/- 6%) protocols that were comparable to fasting-induced reduction in the C session (-12 +/- 3%) (P < 0.05). Furthermore, no differences were found in serum leptin among the MS, MH, SE, and C sessions immediately after exercise and at 30 min of recovery (P > 0.05). Cortisol was higher (P < 0.05) after the MH and SE protocols than after the MS and C sessions. Glucose and growth hormone were higher (P < 0.05) after exercise in the MS, MH, and SE protocols than after the C session. In conclusion, typical resistance exercise protocols designed for development of MS, MH, and SE did not result in serum leptin changes when sampled immediately or 30 min postexercise.     

Similar acute molecular responses to equivalent volumes of isometric, lengthening, or shortening mode resistance exercise.

The present study was undertaken to test the hypothesis that the contraction mode of action [static-isometric (Iso), shortening-concentric (Con), or lengthening-eccentric (Ecc)] used to stress the muscle provides a differential mechanical stimulus eliciting greater or lesser degrees of anabolic response at the initiation of a resistance training program. We performed an acute resistance training study in which different groups of rodents completed four training sessions in either the Iso, Con, or Ecc mode of contraction under conditions of activation and movement specifically designed to elicit equivalent volumes of force accumulation. The results of this experiment indicate that the three modes of contraction produced nearly identical cell signaling, indicative of an anabolic response involving factors such as increased levels of mRNA for IGF-I, procollagen III alpha1, decreased myostatin mRNA, and increased total RNA concentration. The resulting profiles collectively provide evidence that pure mode of muscle action, in and of itself, does not appear to be a primary variable in determining the efficacy of increased loading paradigms with regard to the initiation of selected muscle anabolic responses.     

Acute molecular responses of skeletal muscle to resistance exercise in able-bodied and spinal cord-injured subjects.

Spinal cord injury (SCI) results in muscle atrophy, which contributes to a number of health problems, such as cardiovascular deconditioning, metabolic derangement, and osteoporosis. Electromyostimulation (EMS) holds the promise of ameliorating SCI-related muscle atrophy and, therefore, improving general health. To date, EMS training of long-term SCI subjects has resulted in some muscle hypertrophy but has fallen short of normalizing muscle mass. The aim of this study was to compare the molecular responses of vastus lateralis muscles from able-bodied (AB) and SCI subjects after acute bouts of EMS-induced resistance exercise to determine whether SCI muscles displayed some impairment in response. Analysis included mRNA markers known to be responsive to increased loading in rodent muscles. Muscles of AB and SCI subjects were subjected to EMS-stimulated exercise in two 30-min bouts, separated by a 48-h rest. Needle biopsy samples were obtained 24 h after the second exercise bout. In both the AB and SCI muscles, significant changes were seen in insulin-like growth factor binding proteins 4 and 5, cyclin-dependent kinase inhibitor p21, and myogenin mRNA levels. In AB subjects, the mRNA for mechano-growth factor was also increased. Before exercise, the total RNA concentration of the SCI muscles was less than that of the AB subjects but not different postexercise. The results of this study indicate that acute bouts of resistance exercise stimulate molecular responses in the skeletal muscles of both AB and SCI subjects. The responses seen in the SCI muscles indicate that the systems that regulate these molecular responses are intact, even after extended periods of muscle unloading.     

Selected contribution: Variation and heritability for the adaptational response to exercise in genetically heterogeneous rats.

Adaptational response to aerobic exercise was artificially selected for across one generation in a founder population of 20 female and 20 male genetically heterogeneous rats (N:NIH). Selection for low and high response was based on the change in treadmill running capacity, assessed by meters (m) run to exhaustion before and after 24 days of modest treadmill running. The training response of the founder population averaged +222 m, with wide variation from a negative gain (-) of -110 m to a positive gain (+) of +430 m. Six pairs of the lowest (+13 m) and highest (+327 m) responders were mated. Mean response to training of the low-line (+242 m) offspring did not differ from the founder. The high-selected line gained 383 m from training, +161 m above the founder population. Narrow sense heritability estimated from regression of offspring on midparent values for response to training was 0.43 (P < 0.007). One generation of selection resulted in a 58% divide between the low and high lines. Selectively bred models of both intrinsic (untrained) and adaptation response can be useful in resolving the genetic basis of variation in aerobic capacity.     

Selected contribution: Effects of sex and ovariectomy on responses to platelets in porcine femoral veins.

Estrogen replacement increases risk of venous thrombosis. In this study, we determined responses in vitro to platelets and platelet products in veins from adult male and intact and ovariectomized female pigs. When contracted with prostaglandin F(2alpha), platelets (25,000 platelets/microl) caused relaxation in veins with endothelium. Higher numbers of platelets caused contraction in veins with and without endothelium. In veins without endothelium, contractions were greater in veins from male than in veins from female pigs, and contractions in intact female pig veins were greater than in ovariectomized females pig veins. Platelet products 5-hydroxytryptamine and thromboxane (analog U-46619) caused comparable contractions in all veins; contractions to prostacyclin were less in veins from intact female pigs. ADP caused comparable endothelium-dependent relaxations in all groups. These relaxations were increased by indomethacin in veins from intact males and females; with inhibition of nitric oxide, relaxations were comparable in all groups. These results suggest that venous responses to platelets vary with sex and presence of ovaries in female pigs. These variations reflect differences in type and quantity of substances released from platelets as well as the sensitivity of the smooth muscle to some vasoactive substances. In addition, products of cyclooxygenase may reduce endothelium-dependent relaxations in veins.     

Boophilus microplus: cellular responses to larval attachment and their relationship to host resistance.

The histology of early feeding lesions of the cattle tick B. microplus has been studied using 32P labelled larvae to standardize the duration of attachment. Critical studies were made on 3-h lesions in six separate experiments on different groups of British breed animals. Each group consisted of three animals--one previously unexposed to ticks, one of high resistance and one of low resistance. The degree of mast cell disruption, eosinophil concentration and degranulation, and the extent of epidermal vesiculation were all significantly greater at the site of attachment on highly resistant hosts. In previously unexposed animals there was no mobilization of eosinophils nor mast cell breakdown and no epidermal vesiculation. Possible immune mechanisms producing mast cell disruption and the infiltration and concentration of eosinophils are suggested, and the effect of eosinophil degranulation on larval attachment and feeding is discussed.     

Pituitary-adrenal-gonadal responses to high-intensity resistance exercise overtraining

Weight-trainedmen [OT ; n = 11; age = 22.0 ± 0.9 (SE) yr] resistance trained daily at 100%one-repetition maximum (1-RM) intensity for 2 wk, resulting in 1-RMstrength decrements and in an overtrained state. A control group (Con;n = 6; age = 23.7 ± 2.4 yr)trained 1 day/wk at a low relative intensity (50% 1 RM). After 2 wk,the OT group exhibited slightly increased exercise-induced testosterone(preexercise = 26.5 ± 1.3 nmol/l, postexercise = 29.1 ± 5.9 nmol/l) and testosterone-to-cortisol ratio (preexercise = 0.049 ± 0.007 nmol/l, postexercise = 0.061 ± 0.006 nmol/l) and decreased exercise-induced cortisol (preexercise = 656.1 ± 98.1 nmol/l, postexercise = 503.1 ± 39.7 nmol/l). Serumconcentrations for growth hormone and plasma peptide F[preproenkephalin (107140)] were similar for both groupsthroughout the overtraining period. This hormonal profile is distinctlydifferent from what has been previously reported for other types ofovertraining, indicating that high-relative-intensity resistanceexercise overtraining may not be successfully monitered via circulatingtestosterone and cortisol. Unlike overtraining conditions withendurance athletes, altered resting concentrations of pituitary,adrenal, or gonadal hormones were not evident, and exercise-inducedconcentrations were only modestly affected.

     

Cytokine responses to acute and chronic exercise in multiple sclerosis.

Regular exercise reduces functional loss associated with multiple sclerosis (MS). However, the impact of exercise on inflammatory mediators associated with disease activity remains relatively unexplored. The purpose of this study was to determine whether ambulatory MS subjects would respond similarly to aerobic cycle training compared with matched controls on circulating immune variables, interleukin (IL)-6, tumor necrosis factor (TNF)-alpha and interferon (IFN)-gamma. Eleven MS and 11 non-MS control subjects (8 women and 3 men in both groups) matched in age, height, body mass, body fat, and peak O(2) uptake completed the study. Subjects completed 30 min of cycle ergometry at 60% of peak O(2) uptake, 3 day/wk for 8 wk. Plasma cytokine concentrations were determined before and after exercise at weeks 0, 4, and 8. MS and control subjects showed a similar cytokine responses to exercise. IL-6 at rest tended to decrease (P = 0.08) with training in both groups. Resting plasma TNF-alpha tended to be higher in MS compared with controls throughout the study (P = 0.08). MS subjects showed elevated resting TNF-alpha in MS at the end of the 8-wk program (P = 0.04), whereas resting TNF-alpha remained unchanged in controls (P > 0.05). Resting plasma IFN-gamma at rest was elevated in MS subjects (P = 0.008) and unchanged in controls at the end of the intervention (P > 0.05). The response of plasma IL-6, TNF-alpha, and IFN-gamma after a single bout of exercise was similar between MS and control subjects (P > 0.05). Additional research to understand the impact of exercise on immune variables in MS is warranted.     

The cellular and molecular basis for divergent allergic responses to chemicals.

Chemicals vary with respect to the nature of allergic reactions which they will elicit preferentially. A wide variety of environmental and industrial chemicals are known to cause allergic contact dermatitis (contact sensitivity). Some of these are able also to induce respiratory allergy. This article reviews the characteristics of immune responses to different classes of chemical allergens and the role which functional subpopulations of T helper (TH) cells and their soluble cytokine products play in the induction of allergic sensitization. In addition, new opportunities to identify and classify chemical allergens based upon characterization of divergent allergic responses is discussed.     

Selected contribution: Acute and sustained ventilatory responses to hypoxia in high-altitude natives living at sea level.

High-altitude (HA) natives have blunted ventilatory responses to hypoxia (HVR), but studies differ as to whether this blunting is lost when HA natives migrate to live at sea level (SL), possibly because HVR has been assessed with different durations of hypoxic exposure (acute vs. sustained). To investigate this, 50 HA natives (>3,500 m, for >20 yr) now resident at SL were compared with 50 SL natives as controls. Isocapnic HVR was assessed by using two protocols: protocol 1, progressive stepwise induction of hypoxia over 5-6 min; and protocol 2, sustained (20-min) hypoxia (end-tidal Po(2) = 50 Torr). Acute HVR was assessed from both protocols, and sustained HVR from protocol 2. For HA natives, acute HVR was 79% [95% confidence interval (CI): 52-106%, P = not significant] of SL controls for protocol 1 and 74% (95% CI: 52-96%, P < 0.05) for protocol 2. By contrast, sustained HVR after 20-min hypoxia was only 30% (95% CI: -7-67%, P < 0.001) of SL control values. The persistent blunting of HVR of HA natives resident at SL is substantially less to acute than to sustained hypoxia, when hypoxic ventilatory depression can develop.     

Selected contribution: variation in acute hypoxic ventilatory response is linked to mouse chromosome 9.

Genetic determinants confer variation among inbred mouse strains with respect to the magnitude and pattern of breathing during acute hypoxic challenge. Specifically, inheritance patterns derived from C3H/HeJ (C3) and C57BL/6J (B6) parental strains suggest that differences in hypoxic ventilatory response (HVR) are controlled by as few as two genes. The present study demonstrates that at least one genetic determinant is located on mouse chromosome 9. This genotype-phenotype association was established by phenotyping 52 B6C3F2 (F2) offspring for HVR characteristics. A genome-wide screen was performed using microsatellite DNA markers (n = 176) polymorphic between C3 and B6 mice. By computing log-likelihood values (LOD scores), linkage analysis compared marker genotypes with minute ventilation (&Vdot;E), tidal volume (VT), and mean inspiratory flow (VT/TI, where TI is inspiratory time) during acute hypoxic challenge (inspired O2 fraction = 0.10, inspired CO2 fraction = 0.03 in N2). A putative quantitative trait locus (QTL) positioned in the vicinity of D9Mit207 was significantly associated with hypoxic VE (LOD = 4.5), VT (LOD = 4.0), and VT/TI (LOD = 5.1). For each of the three HVR characteristics, the putative QTL explained more than 30% of the phenotypic variation among F(2) offspring. In conclusion, this genetic model of differential HVR characteristics demonstrates that a locus approximately 33 centimorgans from the centromere on mouse chromosome 9 confers a substantial proportion of the variance in VE, VT, and VT/TI during acute hypoxic challenge.     

Selected contribution: chemoreflex responses to CO2 before and after an 8-h exposure to hypoxia in humans.

The ventilatory sensitivity to CO2, in hyperoxia, is increased after an 8-h exposure to hypoxia. The purpose of the present study was to determine whether this increase arises through an increase in peripheral or central chemosensitivity. Ten healthy volunteers each underwent 8-h exposures to 1) isocapnic hypoxia, with end-tidal PO2 (PET(O2)) = 55 Torr and end-tidal PCO2 (PET(CO2)) = eucapnia; 2) poikilocapnic hypoxia, with PET(O2) = 55 Torr and PET(CO2) = uncontrolled; and 3) air-breathing control. The ventilatory response to CO2 was measured before and after each exposure with the use of a multifrequency binary sequence with two levels of PET(CO2): 1.5 and 10 Torr above the normal resting value. PET(O2) was held at 250 Torr. The peripheral (Gp) and the central (Gc) sensitivities were calculated by fitting the ventilatory data to a two-compartment model. There were increases in combined Gp + Gc (26%, P < 0.05), Gp (33%, P < 0.01), and Gc (23%, P = not significant) after exposure to hypoxia. There were no significant differences between isocapnic and poikilocapnic hypoxia. We conclude that sustained hypoxia induces a significant increase in chemosensitivity to CO2 within the peripheral chemoreflex.     

Invited review: Effects of acute exercise and exercise training on insulin resistance.

Insulin resistance of skeletal muscle glucose transport is a key defect in the development of impaired glucose tolerance and Type 2 diabetes. It is well established that both an acute bout of exercise and chronic endurance exercise training can have beneficial effects on insulin action in insulin-resistant states. This review summarizes the present state of knowledge regarding these effects in the obese Zucker rat, a widely used rodent model of obesity-associated insulin resistance, and in insulin-resistant humans with impaired glucose tolerance or Type 2 diabetes. A single bout of prolonged aerobic exercise (30-60 min at approximately 60-70% of maximal oxygen consumption) can significantly lower plasma glucose levels, owing to normal contraction-induced stimulation of GLUT-4 glucose transporter translocation and glucose transport activity in insulin-resistant skeletal muscle. However, little is currently known about the effects of acute exercise on muscle insulin signaling in the postexercise state in insulin-resistant individuals. A well-established adaptive response to exercise training in conditions of insulin resistance is improved glucose tolerance and enhanced skeletal muscle insulin sensitivity of glucose transport. This training-induced enhancement of insulin action is associated with upregulation of specific components of the glucose transport system in insulin-resistant muscle and includes increased protein expression of GLUT-4 and insulin receptor substrate-1. It is clear that further investigations are needed to further elucidate the specific molecular mechanisms underlying the beneficial effects of acute exercise and exercise training on the glucose transport system in insulin-resistant mammalian skeletal muscle.     

Twenty-four-hour metabolic responses to resistance exercise in women

Seven nonobese adult females (40 +/- 8 years) were studied in a room calorimeter on a day that resistance exercise (REX) was performed (4 sets of 10 exercises) and on a nonexercise control day (CON). Twenty-four-hour energy expenditure (EE) on the REX day (mean +/- SD, 2,328 +/- 327 kcal.d(-1)) was greater than CON (2,001 +/- 369 kcal.d(-1), p < 0.001). The net increase in EE during and immediately after (30 minutes) exercise represented 76 +/- 12% of the total increase in 24-hour EE. Twenty four-hour RQ on the REX day (0.86 +/- 0.06) did not differ from CON (0.87 +/- 0.02). Twenty four-hour carbohydrate oxidation was elevated on the REX day, but 24-hour fat and protein oxidation were not different. Thus, in women, the increase in EE due to resistance exercise is largely seen during and immediately after the exercise. The increased energy demand is met by increased carbohydrate oxidation, with no increase in 24-hour fat oxidation.     

Acute testosterone and cortisol responses to high power resistance exercise

This study examined the acute hormonal responses to a single high power resistance exercise training session. Four weight trained men (X ± SD; age [yrs] = 24.5 ± 2.9; hgt [m] = 1.82 ± 0.05; BW [kg] = 96.9 ± 10.6; 1 RM barbell squat [kg] = 129.3 ± 17.4) participated as subjects in two randomly ordered sessions. During the lifting session, serum samples were collected pre- and 5 min post-exercise, and later analyzed for testosterone (Tes), cortisol (Cort), their ratio (Tes/Cort), and lactate (HLa). The lifting protocol was 10 × 5 speed squats at 70% of system mass (1 RM + BW) with 2 min inter-set rest intervals. Mean power and velocity were determined for each repetition using an external dynamometer. On the control day, the procedures and times (1600–1900 h) were identical except the subjects did not lift. Tes and Cort were analyzed via EIA. Mean ± SD power and velocity was 1377.1 ± 9.6 W and 0.79 ± 0.01 m s⁻¹ respectively for all repetitions, and did not decrease over the 10 sets (p < 0.05). Although not significant, post-exercise Tes exhibited a very large effect size (nmol L⁻¹; pre = 12.5 ± 2.9, post = 20.0 ± 3.9; Cohen’s D = 1.27). No changes were observed for either Cort or the Tes/Cort ratio. HLa significantly increased post-exercise (mmol L⁻¹; pre = 1.00 ± 0.09, post = 4.85 ± 1.10). The exercise protocol resulted in no significant changes in Tes, Cort or the Tes/Cort ratio, although the Cohen’s D value indicates a very large effect size for the Tes response. The acute increase for Tes is in agreement with previous reports that high power activities can elicit a Tes response. High power resistance exercise protocols such as the one used in the present study produce acute increases of Tes. These results indicate that high power resistance exercise can contribute to an anabolic hormonal response with this type of training, and may partially explain the muscle hypertrophy observed in athletes who routinely employ high power resistance exercise.     

Hormonal and growth factor responses to heavy resistance exercise protocols

To examine endogenous anabolic hormone and growth factor responses to various heavy resistance exercise protocols (HREPs), nine male subjects performed each of six randomly assigned HREPs, which consisted of identically ordered exercises carefully designed to control for load [5 vs. 10 repetitions maximum (RM)], rest period length (1 vs. 3 min), and total work effects. Serum human growth hormone (hGH), testosterone (T), somatomedin-C (SM-C), glucose, and whole blood lactate (HLa) concentrations were determined preexercise, midexercise (i.e., after 4 of 8 exercises), and at 0, 5, 15, 30, 60, 90, and 120 min postexercise. All HREPs produced significant (P less than 0.05) temporal increases in serum T concentrations, although the magnitude and time point of occurrence above resting values varied across HREPs. No differences were observed for T when integrated areas under the curve (AUCs) were compared. Although not all HREPs produced increases in serum hGH, the highest responses were observed consequent to the H10/1 exercise protocol (high total work, 1 min rest, 10-RM load) for both temporal and time integrated (AUC) responses. The pattern of SM-C increases varied among HREPs and did not consistently follow hGH changes. Whereas temporal changes were observed, no integrated time (AUC) differences between exercise protocols occurred. These data indicate that the release patterns (temporal or time integrated) observed are complex functions of the type of HREPs utilized and the physiological mechanisms involved with determining peripheral circulatory concentrations (e.g., clearance rates, transport, receptor binding). All HREPs may not affect muscle and connective tissue growth in the same manner because of possible differences in hormonal and growth factor release.     

Effects of low-intensity resistance exercise under acute systemic hypoxia on hormonal responses

Previous studies have shown that low-intensity resistance exercises with vascular occlusion and slow movement effectively increase muscular size and strength. Researchers have speculated that local hypoxia by occlusion and slow movement may contribute to such adaptations via promoting anabolic hormone secretions by the local accumulation of metabolites. In this study, we determined the effects of low-intensity resistance exercise under acute systemic hypoxia on metabolic and hormonal responses. Eight male subjects participated in 2 experimental trials: (a) low-intensity resistance exercise while breathing normoxic air (normoxic resistance exercise [NR]), (b) low-intensity resistance exercise while breathing 13% oxygen (hypoxic resistance exercise [HR]). The resistance exercises (bench press and leg press) consisted of 14 repetitions for 5 sets at 50% of maximum strength with 1 minute of rest between sets. Blood lactate (LA), serum growth hormone (GH), norepinephrine (NE), testosterone, and cortisol concentrations were measured before normoxia and hypoxia exposures; 15 minutes after the exposures; and at 0, 15, and 30 minutes after the exercises. The LA levels significantly increased after exercises in both trials (p ≤ 0.05). The area under the curve for LA after exercises was significantly higher in the HR trial than in the NR trial (p ≤ 0.05). The GH significantly increased only after the HR trial (p ≤ 0.05). The NE and testosterone significantly increased after the exercises in both trials (p ≤ 0.05). Cortisol did not significantly change in both trials. These results suggest that low-intensity resistance exercise in the hypoxic condition caused greater metabolic and hormonal responses than that in the normoxic condition. Coaches may consider low-intensity resistance exercise under systemic hypoxia as a potential training method for athletes who need to maintain muscle mass and strength during the long in-season.