Oxidative removal of lactate after strenuous exercise

Metabolic fate of lactate after strenuous exercise which lasted 2-3 min was investigated in rats and mice. 14C-labeled lactate or glucose was injected into the aorta of rats through an catheter. 14C-glucose was injected intraperitoneally into the mice after supramaximal exercise. The mice ran twice with a 4 hr interval to investigate muscle 14C-lactate metabolism which was produced from muscle 14C-glycogen. A great deal of blood and muscle 14C-lactate was expired as 14CO2 after the exercise. The results indicate that oxidative removal is the major fate of lactate metabolism after strenuous exercise and that blood glucose is the major substrate for muscle glycogen resynthesis. Light intensity exercise after strenuous exercise (active recovery) enhances oxidative removal of blood and muscle lactate. Gluconeogenesis from lactate to glycogen within the skeletal muscle is not a major pathway of muscle lactate metabolism, while high intensity training can activate this pathway.     

Do invading leucocytes contribute to the decrease in glutathione concentrations indicating oxidative stress in exercised muscle, or are they important for its recovery?

Mice were subjected to one session of strenuous running exercise and their soleus muscles were examined in respect of changes in ultrastructure and to their concentration of reduced glutathione [GSH] which are indicators of oxidative stress. It was hypothesized that invading leucocytes contributed to oxidative stress and they were functionally inhibited in one experimental group by the administration of colchicine. Exercise led to an immediate decrease in [GSH] of about 60%, which slowly recovered during 96 h after exercise. With the administration of colchicine after exercise, [GSH] was higher than in the untreated exercise group 48 h after exercise, indicating an inhibition of the ability of leucocytes to produce oxidative stress. However, at 96 h after exercise, [GSH] was lower in the treated exercise group than in the untreated group. The morphological evaluation of the percentage of affected fibres showed that the invasion of leucocytes increased muscle fibre damage. The results suggested that invading leucocytes enhanced production of reactive species of oxygen that may have participated in inducing muscle damage. However, inhibition of leucocyte invasion did not permit their scavenger action of removing cell debris, which appeared to produce even more oxidative stress in the muscle.     

Abnormal collagen synthesis in skeletal muscle of dystrophic chicken

Specific molecular properties of skeletal muscle collagens from normal and dystrophic chickens have been compared. When dystrophy develops in skeletal muscle tissue there was an increase in the amount of total collagen and an increased proportion of Type III collagen in the tissue. The results from the cross-link study as well as the analysis of the solubility of collagen showed that skeletal muscle of dystrophic chicken produces more immature collagen fibers compared to normal chicken. These findings strongly indicate an important role of collagen in the pathogenesis of the extensive connective tissue prolipheration characteristic of muscular dystrophies.     

Exercise,but not quercetin,ameliorates inflammation,mitochondrial biogenesis,and lipid metabolism in skeletal muscle after strenuous exercise by high-fat diet mice

[Purpose]

The purpose of this study was to investigate whether moderate exercise and quercetin intake with a low fat diet contribute to inflammatory cytokine production, mitochondrial biogenesis, and lipid metabolism in skeletal muscle after strenuous exercise by high-fat diet mice.

[Methods]

Male C57BL/6 mice were randomly divided into four groups: (1) High-fat for 12 weeks and low-fat diet control (C; n = 6); (2) high-fat diet for 12 weeks and low-fat diet with quercetin (Q; n = 4); (3) high-fat diet for 12 weeks and low-fat diet with exercise (E; n = 4); or (4) high-fat diet for 12 weeks and low-fat diet with exercise and quercetin (EQ; n = 5). Quercetin (10 mg/kg) was administered once per day, 5 day/week for 8 weeks. Exercise training was performed at moderate intensity for 8 weeks, 5 days/week for 30–60 min/day. Mice were subjected to a strenuous exercise bout of 60 min at a speed of 25 m/min (VO₂ max 85%) conducted as an exercise-induced fatigue just before sacrifice.

[Results]

As results, body weights were significantly different among the groups. Exercise training significantly reduced inflammatory cytokines after strenuous exercise in skeletal muscle of high-fat diet mice. Exercise training increased Tfam mRNA in the soleus muscle after strenuous exercise. Exercise training significantly decreased lipogenesis markers in skeletal muscle of obese mice after strenuous exercise. Moderate exercise significantly increased lipolysis markers in the tibialis anterior muscle.

[Conclusion]

These findings suggest that exercise training reduced inflammatory cytokine levels and improved mitochondrial biogenesis and lipid metabolism. However quercetin supplementation did not affect these parameters. Thus, long-term moderate exercise training has positive effects on obesity.     

Cardiac,skeletal muscle and serum irisin responses to with or without water exercise in young and old male rats: Cardiac muscle produces more irisin than skeletal muscle

Irisin converts white adipose tissue (WAT) into brown adipose tissue (BAT), as regulated by energy expenditure. The relationship between irisin concentrations after exercise in rats compared humans after exercise remains controversial. We therefore: (1) measured irisin expression in cardiac and skeletal muscle, liver, kidney, peripheral nerve sheath and skin tissues, as also serum irisin level in 10 week-old rats without exercise, and (2) measured tissue supernatant irisin levels in cardiac and skeletal muscle, and in response to exercise in young and old rats to establishing which tissues produced most irisin. Young (12 months) and old rats (24 months) with or without 10 min exercise (water floating) and healthy 10 week-old Sprague-Dawley rats without exercise were used. Irisin was absent from sections of skeletal muscle of unexercised rats, the only part being stained being the perimysium. In contrast, cardiac muscle tissue, peripheral myelin sheath, liver, kidneys, and skin dermis and hypodermis were strongly immunoreactivity. No irisin was seen in skeletal muscle of unexercised young and old rats, but a slight amount was detected after exercise. Strong immunoreactivity occurred in cardiac muscle of young and old rats with or without exercise, notably in pericardial connective tissue. Serum irisin increased after exercise, being higher in younger than older rats. Irisin in tissue supernatants (cardiac and skeletal muscle) was high with or without exercise. High supernatant irisin could come from connective tissues around skeletal muscle, especially nerve sheaths located within it. Skeletal muscle is probably not a main irisin source.     

Antioxidant effect of diphenyl diselenide on oxidative stress caused by acute physical exercise in skeletal muscle and lungs of mice

This study was designed to examine if diphenyl diselenide (PhSe)₂, an organoselenium compound, attenuates oxidative stress caused by acute physical exercise in skeletal muscle and lungs of mice. Swiss mice were pre‐treated with (PhSe)₂ (5 mg kg^‐1 day^‐1) for 7 days. At the 7th day, the animals were submitted to acute physical exercise which consisted of continuous swimming for 20 min. The animals were euthanized 1 and 24 h after the exercise test. The levels of thiobarbituric acid reactive species (TBARS), non‐protein thiols (NPSH) and ascorbic acid and the activity of catalase (CAT) were measured in the lungs and skeletal muscle of mice. Glycogen content was determined in the skeletal muscle of mice. Parameters in plasma (urea and creatinine) were determined. The results demonstrated an increase in TBARS levels induced by acute physical exercise in the skeletal muscle and lungs of mice. Animals submitted to exercise showed an increase in non‐enzymatic antioxidant defenses (NPSH and ascorbic acid) in the skeletal muscle. In lungs of mice, activity of CAT was increased. (PhSe)₂ protected against the increase in TBARS levels and ameliorated antioxidant defenses in the skeletal muscle and lungs of mice submitted to physical exercise. These results indicate that acute physical exercise caused a tissue‐specific oxidative stress in the skeletal muscle and lungs of mice. (PhSe)₂ protected against oxidative damage induced by acute physical exercise in mice. Copyright © 2009 John Wiley & Sons, Ltd.     

Physical exercise stimulates autophagy in normal skeletal muscles but is detrimental for collagen VI-deficient muscles

Autophagy is a catabolic process that provides the degradation of altered/damaged organelles through the fusion between autophagosomes and lysosomes. Proper regulation of the autophagic flux is fundamental for the homeostasis of skeletal muscles in physiological conditions and in response to stress. Defective as well as excessive autophagy is detrimental for muscle health and has a pathogenic role in several forms of muscle diseases. Recently, we found that defective activation of the autophagic machinery plays a key role in the pathogenesis of muscular dystrophies linked to collagen VI. Impairment of the autophagic flux in collagen VI null (Col6a1–/–) mice causes accumulation of dysfunctional mitochondria and altered sarcoplasmic reticulum, leading to apoptosis and degeneration of muscle fibers. Here we show that physical exercise activates autophagy in skeletal muscles. Notably, physical training exacerbated the dystrophic phenotype of Col6a1–/– mice, where autophagy flux is compromised. Autophagy was not induced in Col6a1–/– muscles after either acute or prolonged exercise, and this led to a marked increase of muscle wasting and apoptosis. These findings indicate that proper activation of autophagy is important for muscle homeostasis during physical activity.     

The serum levels of growth factors: PDGF, TGF-beta and VEGF are increased after strenuous physical exercise.

Strenuous physical exercise induces muscle fibers damage and non-specific inflammatory response. Activated by inflammatory process cells may serve as the source of wide spectrum of inflammatory mediators and growth factors. Namely Platelet Derived Growth Factor (PDGF), Transforming Growth Factor-beta (TGF-beta) and Vascular Endothelial Growth Factor (VEGF) could be released. The aim of present study was to assess the impact of physical exercise on growth factors generation in healthy young people. 14 young sportsmen were enrolled into the study. They performed strenuous physical exercise. Blood samples were drawn before, immediately after, and 2 hours after the exercise bout. Serum PDGF, TGF-beta and VEGF concentrations were measured using commercially available ELISA kit based on immunoenzimatic method. Serum level of PDGF increased significantly from 1.7 ng/ml before to 4.64 ng/ml (2.73-fold) immediately after, and to 3.3 ng/ml (1.94-fold) 2 hours after exertion. Serum level of TGF-beta increased significantly from 20.58 ng/ml before to 55.37 ng/ml (2.7-fold) immediately after, and to 40.03 ng/ml (1.95-fold) 2 hours after exertion. Serum level of VEGF increased significantly from 91.83 pg/ml before to 165.61 pg/ml (1.8-fold) immediately after the exercise. Two hours after the exertion serum level of VEGF was 137.22 pg/ml, what is 1.49-fold above the basal level; however not being significantly different. In summery, observed increased level of growth factors could be involved in the process of adaptation of human organism to physical training. In addition, in the context of the role of inflammation in the pathogenesis of various diseases, our results point to the potentially deleterious effect of strenuous physical exercise.     

Up-regulation of mitogen activated protein kinases in mdx skeletal muscle following chronic treadmill exercise

Dystrophin, a product of the Duchenne muscular dystrophy gene, is a cytoskeletal protein of skeletal and cardiac muscle fibers. Dystrophin-deficient muscle fibers are abnormally vulnerable to mechanical stress including physical exercise, which is a powerful stimulator of mitogen-activated protein kinases (MAPKs). To examine how treadmill exercise affects MAPK family members in dystrophin-deficient skeletal muscle, we subjected both mdx mice, an animal model for Duchenne muscular dystrophy, and C57BL/10 mice to treadmill exercise and examined the phosphorylated protein levels of extracellular-signal regulated kinase (ERK1/2), p38 MAPK and c-Jun N terminal kinase 1 and 2 (JNK1 and JNK2) in the gastrocnemius muscle. Phosphorylation of ERK1/2, p38 MAPK and JNK2, but not JNK1, increased more in the muscles of exercise trained mdx mice than in muscles of trained C57BL/10 or untrained mdx mice. These results show that physical exercise aberrantly up-regulates the phosphorylated form of ERK1/2, p38 MAPK and JNK2 in dystrophin-deficient skeletal muscle and that their up-regulation might play a role in the degeneration and regeneration process of dystrophic features.     

Physical exercise stimulates autophagy in normal skeletal muscles but is detrimental for collagen VI-deficient muscles

Autophagy is a catabolic process that provides the degradation of altered/damaged organelles through the fusion between autophagosomes and lysosomes. Proper regulation of the autophagic flux is fundamental for the homeostasis of skeletal muscles in physiological conditions and in response to stress. Defective as well as excessive autophagy is detrimental for muscle health and has a pathogenic role in several forms of muscle diseases. Recently, we found that defective activation of the autophagic machinery plays a key role in the pathogenesis of muscular dystrophies linked to collagen VI. Impairment of the autophagic flux in collagen VI null (Col6a1–/–) mice causes accumulation of dysfunctional mitochondria and altered sarcoplasmic reticulum, leading to apoptosis and degeneration of muscle fibers. Here we show that physical exercise activates autophagy in skeletal muscles. Notably, physical training exacerbated the dystrophic phenotype of Col6a1–/– mice, where autophagy flux is compromised. Autophagy was not induced in Col6a1–/– muscles after either acute or prolonged exercise, and this led to a marked increase of muscle wasting and apoptosis. These findings indicate that proper activation of autophagy is important for muscle homeostasis during physical activity.     

Effects of strenuous maternal exercise on fetal organ weights and skeletal muscle development in rats

The purpose of the present study was to observe the effects of strenuous maternal aerobic exercise throughout gestation on fetal outcome in the rat. The strenuous exercise intensity consisted of a treadmill speed of 30 m.min-1 on a 10 degrees incline, for 120 min.day-1, 5 days.week-1. The rats were conditioned to run on a motor-driven treadmill by following a progressive two-week exercise program, so that by the end of the two weeks the rats were capable of running comfortably at this strenuous intensity in the non-pregnant state. Following the two-week running programme, the rats were paired by weight and randomly assigned to either a pregnant group that continued the running program throughout gestation (pregnant runner), or a pregnant group that did not continue the running program throughout pregnancy (pregnant control). At birth the neonates born to the pregnant running group did not differ in average neonatal body weight values, number per litter or total litter weight values when compared to controls, nor were superficial gross abnormalities observed in neonates born to the pregnant control or pregnant running groups. The strenuous maternal exercise intensity did not alter neonatal organ weight values (brain, heart, liver, lung, kidney), nor neonatal skeletal muscle (gastrocnemius, sternomastoid, diaphragm) when compared to control values. It is suggested that maternal exercise of this intensity throughout gestation does not affect fetal outcome in the rat, and may be due to the animals accustomization to the strenuous exercise protocol prior to pregnancy.     

Effects of reactive oxygen species and interplay of antioxidants during physical exercise in skeletal muscles

A large number of researches have led to a substantial growth of knowledge about exercise and oxidative stress. Initial investigations reported that physical exercise generates free radical-mediated damages to cells; however, in recent years, studies have shown that regular exercise can upregulate endogenous antioxidants and reduce oxidative damage. Yet, strenuous exercise perturbs the antioxidant system by increasing the reactive oxygen species (ROS) content. These alterations in the cellular environment seem to occur in an exercise type-dependent manner. The source of ROS generation during exercise is debatable, but now it is well established that both contracting and relaxing skeletal muscles generate reactive oxygen species and reactive nitrogen species. In particular, exercises of higher intensity and longer duration can cause oxidative damage to lipids, proteins, and nucleotides in myocytes. In this review, we summarize the ROS effects and interplay of antioxidants in skeletal muscle during physical exercise. Additionally, we discuss how ROS-mediated signaling influences physical exercise in antioxidant system.     

MRI analysis of structural changes in skeletal muscles and surrounding tissues following long-term walking exercise with training equipment

Muscular recovery after exercise is an important topic in sports medicine, and accurate and quantitative measurements of changes in muscle are required to assess muscular recovery. In the present study, we report a new analytical method to measure muscular changes quantitatively. The technique consists of three independent methods: image processing of two-dimensional MR images, morphological analysis using three-dimensional MR images, and diffusion tensor MRI. Using this method, we investigated changes in the quadriceps and biceps femoris and gluteus maximus muscles and surrounding tissues before and after 1 mo of exercise wearing training equipment. The subjects were 21 healthy adult female volunteers, 14 of whom wore training equipment and 7 who wore normal equipment. The percentage of adipose tissue in muscle after exercise in subjects who wore training equipment was on average 4.4% (P < 0.001) lower than that before exercise, and the peak point of the dorsal hip after exercise with use of the equipment was on average 10.8 mm higher than that before exercise. Further, the fractional anisotropy of water diffusion in muscles increased by an average of 0.039 (P < 0.001) after exercise with use of training equipment. In contrast, there was no significant difference before and after exercise in subjects who wore normal equipment. These results show that walking exercise while wearing training equipment thickens and tightens the muscular fiber tissues. This noninvasive measurement approach may allow quantitation of the athletic ability of the muscles, which is not measured conventionally, and is an effective method for analyzing skeletal muscles.     

Induction and adaptation of chaperone-assisted selective autophagy CASA in response to resistance exercise in human skeletal muscle

Chaperone-assisted selective autophagy (CASA) is a tension-induced degradation pathway essential for muscle maintenance. Impairment of CASA causes childhood muscle dystrophy and cardiomyopathy. However, the importance of CASA for muscle function in healthy individuals has remained elusive so far. Here we describe the impact of strength training on CASA in a group of healthy and moderately trained men. We show that strenuous resistance exercise causes an acute induction of CASA in affected muscles to degrade mechanically damaged cytoskeleton proteins. Moreover, repeated resistance exercise during 4 wk of training led to an increased expression of CASA components. In human skeletal muscle, CASA apparently acts as a central adaptation mechanism that responds to acute physical exercise and to repeated mechanical stimulation.     

Exercise-induced increase in the capacity of rat skeletal muscle to oxidize ketones.

During and after strenuous prolonged exercise, sedentary individuals develop high blood levels of acetoacetate and beta-hydroxybutyrate whereas exercise-trained animals and human subjects do not. We have investigated the possibility that exercise training can increase the capacity of skeletal muscle to oxidize ketones. In this study we measured rates of D-beta[3-14-C]-hydroxybutyrate and [3-14-C]acetoacetate oxidation, and the levels of activity of the enzymes involved in the oxidation of ketones in homogenates of gastrocnemius muscles of exercise-trained and of untrained male rats. The trained animals had markedly lower blood ketone levels immediately and 60 min after a 90 min long bout of exercise than did the sedentary animals. The rates of D-beta-[13-14C]hydroxybutryate and [3-14-C]acetoacetate oxidation were twice as high in homogenates of muscles from the trained as compared to the sedentary rats. The increases in levels of activity in gastrocnemius muscle in response to the exercise program were: beta-hydroxybutyrate dehydrogenase threefold; 3-ketoacid CoA-transferase twofold; and acetoacetyl-CoA thiolase 55%. This exercise-induced increase in the capacity of skeletal muscle to oxidize ketones could play a role in preventing development of ketosis in the physically trained animal during and following prolonged strenuous exercise.     

Inflammatory markers CD11b, CD16, CD66b, CD68, myeloperoxidase and neutrophil elastase in eccentric exercised human skeletal muscles

The aim of the present study was to investigate leucocyte markers, CD11b, CD16, CD66b, CD68, myeloperoxidase and neutrophil elastase on skeletal muscle biopsies from biceps brachii after unaccustomed eccentric exercise followed by the second bout of exercise 3 weeks later. The subjects (10 subjects received COX-2 inhibitor (Celecoxib) and 13 subjects received placebo) were divided into three categories: mild, moderate and severe effect of eccentric exercise, according to the reduction and recovery of muscle force-generating capacity after performing 70 maximal eccentric actions with elbow flexors on an isokinetic dynamometer. The results showed that the CD66b antibody was applicable for localization of neutrophils in human skeletal muscle, whereas the other studied neutrophil markers recognized also other leucocytes than neutrophils. The number of CD66b positive cells in skeletal muscle was very low and was not affected by the exercise. The macrophage marker CD68 showed reactivity also against satellite cells and fibroblast-like cells in skeletal muscle and therefore cannot be applied as a quantitative value for inflammatory cells. Skeletal muscle fibre injury, shown as dystrophin negative fibres, was observed approximately in half of the biopsies at 4 and 7 days after the first exercise bout in the categories moderate and severe effect of eccentric exercise. These subjects represent the most prominent loss in muscle force-generating capacity both at the category and the individual levels. Furthermore, deformed skeletal muscle fibres were observed in five subjects in these categories after the second bout of exercise. The present results suggest that neutrophils are not involved in skeletal muscle fibre injury and the reduction in muscle force-generating capacity after a single bout of eccentric exercise is a good indirect indicator of muscle damage in humans. Furthermore, prolonged regeneration process could be one of the reasons for impaired peripheral muscle function after high-force eccentric exercise.     

Exercise-induced oxidative stress in humans: cause and consequences

The observation that muscular exercise is associated with oxidative stress in humans was first reported over 30 years ago. Since this initial report, numerous studies have confirmed that prolonged or high-intensity exercise results in oxidative damage to macromolecules in both blood and skeletal muscle. Although the primary tissue(s) responsible for reactive oxygen species (ROS) production during exercise remains a topic of debate, compelling evidence indicates that muscular activity promotes oxidant production in contracting skeletal muscle fibers. Mitochondria, NADPH oxidase, PLA₂-dependent processes, and xanthine oxidase have all been postulated to contribute to contraction-induced ROS production in muscle but the primary site of contraction-induced ROS production in muscle fibers remains unclear. Nonetheless, contraction-induced ROS generation has been shown to play an important physiological function in the regulation of both muscle force production and contraction-induced adaptive responses of muscle fibers to exercise training. Although knowledge in the field of exercise and oxidative stress has grown markedly during the past 30 years, this area continues to expand and there is much more to be learned about the role of ROS as signaling molecules in skeletal muscle.     

Exercise capacity of mice genetically lacking muscle glycogen synthase: in mice, muscle glycogen is not essential for exercise

The glucose storage polymer glycogen is generally considered to be an important source of energy for skeletal muscle contraction and a factor in exercise endurance. A genetically modified mouse model lacking muscle glycogen was used to examine whether the absence of the polysaccharide affects the ability of mice to run on a treadmill. The MGSKO mouse has the GYS1 gene, encoding the muscle isoform of glycogen synthase, disrupted so that skeletal muscle totally lacks glycogen. The morphology of the soleus and quadriceps muscles from MGSKO mice appeared normal. MGSKO-null mice, along with wild type littermates, were exercised to exhaustion. There were no significant differences in the work performed by MGSKO mice as compared with their wild type littermates. The amount of liver glycogen consumed during exercise was similar for MGSKO and wild type animals. Fasting reduced exercise endurance, and after overnight fasting, there was a trend to reduced exercise endurance for the MGSKO mice. These studies provide genetic evidence that in mice muscle glycogen is not essential for strenuous exercise and has relatively little effect on endurance.     

Plasmatic markers of muscular stress in isokinetic exercise

In this paper we examined the variations of plasmatic concentrations of hypoxanthine and xanthine, and their relation with other important indicators of muscular stress creatine-kinase (CK), myoglobin, uric acid, leucocytes, in prolonged, isokynetic physical exercise, performed in a concentric mode at different joint excursion. Twenty healthy male subjects performed isokinetic exercises in concentric-concentric mode, with joint excursion of 30, 60, 90 deg/sec. Blood samples were drawn at rest, immediately after exercise and after 45 min of recovery. The plasmatic concentration of hypoxanthine increased at the end of physical exercise, compared to the rest value of about 1,5 micromol/L, up to a level of greater than 19 micromol/L; the values were higher after a period of recovery of 45 min and the increase varies considerably according to the type of exercise that was performed. Myoglobin has a slight but sensible increment too, with the same trend as hypoxanthine, while CK increase without correlation to the type of exercises. The relation with other indicators of muscular activity demonstrates that in none of the different isokinetic exercises, performed at concentric mode, was there ultrastructural damage, while it is possible to come across a considerable metabolic stress, which is dissimilar in the different kinds of exercises. The results suggest that hypoxanthine can be useful in monitoring the effectiveness of a work load and the metabolic stress consequences on the muscle tissue in training or rehabilitation programs. The results also suggest that even myoglobin, at small concentrations, can have the same function.     

Effect of exercise, training, and glycogen availability on IL-6 receptor expression in human skeletal muscle.

The cytokine interleukin-6 (IL-6) exerts it actions via the IL-6 receptor (IL-6R) in conjunction with the ubiquitously expressed gp130 receptor. IL-6 is tightly regulated in response to exercise, being affected by factors such as exercise intensity and duration, as well as energy availability. Although the IL-6 response to exercise has been extensively studied, little is known about the regulation of the IL-6R response. In the present study, we aimed to investigate the effect of exercise, training, and glycogen availability, factors known to affect IL-6, on the regulation of gene expression of the IL-6R in human skeletal muscle. Human subjects performed either 10 wk of training with an acute exercise bout before and after the training period, or a low-glycogen vs. normal-glycogen acute exercise trial. The IL-6R mRNA response was evaluated in both trials. In response to acute exercise, an increase in IL-6R mRNA levels was observed. Neither training nor intramuscular glycogen levels had an effect on the IL-6R mRNA response to exercise. However, after 10 wk of training, the skeletal muscle expressed a higher mRNA level of IL-6R compared with before training. The present study demonstrated that the IL-6R gene expression levels in skeletal muscle are increased in response to acute exercise, a response that is very well conserved, being affected by neither training status nor intramuscular glycogen levels, as opposed to IL-6. However, after the training period, IL-6R mRNA production was increased in skeletal muscle, suggesting a sensitization of skeletal muscle to IL-6 at rest.