Showing papers in "Journal of Applied Physiology in 2007"
TL;DR: Although elite athletes are not clinically immune deficient, it is possible that the combined effects of small changes in several immune parameters may compromise resistance to common minor illnesses, such as upper respiratory tract infection.
Abstract: Regular moderate exercise is associated with a reduced incidence of infection compared with a completely sedentary state. However, prolonged bouts of strenuous exercise cause a temporary depression of various aspects of immune function (e.g., neutrophil respiratory burst, lymphocyte proliferation, monocyte antigen presentation) that usually lasts ∼3–24 h after exercise, depending on the intensity and duration of the exercise bout. Postexercise immune function dysfunction is most pronounced when the exercise is continuous, prolonged (>1.5 h), of moderate to high intensity (55–75% maximum O2 uptake), and performed without food intake. Periods of intensified training (overreaching) lasting 1 wk or more may result in longer lasting immune dysfunction. Although elite athletes are not clinically immune deficient, it is possible that the combined effects of small changes in several immune parameters may compromise resistance to common minor illnesses, such as upper respiratory tract infection. However, this may ...
941 citations
TL;DR: The present review focuses on muscle-derived cytokines, their regulation by exercise, and their possible roles in metabolism and skeletal muscle function and it discusses which cytokines should be classified as true myokines.
Abstract: During the past 20 yr, it has been well documented that exercise has a profound effect on the immune system. With the discovery that exercise provokes an increase in a number of cytokines, a possible link between skeletal muscle contractile activity and immune changes was established. For most of the last century, researchers sought a link between muscle contraction and humoral changes in the form of an "exercise factor," which could mediate some of the exercise-induced metabolic changes in other organs such as the liver and the adipose tissue. We suggest that cytokines and other peptides that are produced, expressed, and released by muscle fibers and exert either paracrine or endocrine effects should be classified as "myokines." Since the discovery of interleukin (IL)-6 release from contracting skeletal muscle, evidence has accumulated that supports an effect of IL-6 on metabolism. We suggested that muscle-derived IL-6 fulfils the criteria of an exercise factor and that such classes of cytokines should be named "myokines." Interestingly, recent research demonstrates that skeletal muscles can produce and express cytokines belonging to distinctly different families. Thus skeletal muscle has the capacity to express several myokines. To date the list includes IL-6, IL-8, and IL-15, and contractile activity plays a role in regulating the expression of these cytokines in skeletal muscle. The present review focuses on muscle-derived cytokines, their regulation by exercise, and their possible roles in metabolism and skeletal muscle function and it discusses which cytokines should be classified as true myokines.
700 citations
TL;DR: In this paper, a 35-day high-intensity resistance training (RT) program was used to assess the early changes in muscle size and architecture during a bilateral leg extension three times per week on a gravity-independent flywheel ergometer.
Abstract: The onset of whole muscle hypertrophy in response to overloading is poorly documented. The purpose of this study was to assess the early changes in muscle size and architecture during a 35-day high-intensity resistance training (RT) program. Seven young healthy volunteers performed bilateral leg extension three times per week on a gravity-independent flywheel ergometer. Cross-sectional area (CSA) in the central (C) and distal (D) regions of the quadriceps femoris (QF), muscle architecture, maximal voluntary contraction (MVC), and electromyographic (EMG) activity were measured before and after 10, 20, and 35 days of RT. By the end of the training period, MVC and EMG activity increased by 38.9 ± 5.7 and 34.8% ± 4.7%, respectively. Significant increase in QF CSA (3.5 and 5.2% in the C and D regions, respectively) was observed after 20 days of training, along with a 2.4 ± 0.7% increase in fascicle length from the 10th day of training. By the end of the 35-day training period, the total increase in QF CSA for regions C and D was 6.5 ± 1.1 and 7.4 ± 0.8%, respectively, and fascicle length and pennation angle increased by 9.9 ± 1.2 and 7.7 ± 1.3%, respectively. The results show for the first time that changes in muscle size are detectable after only 3 wk of RT and that remodeling of muscle architecture precedes gains in muscle CSA. Muscle hypertrophy seems to contribute to strength gains earlier than previously reported; flywheel training seems particularly effective for inducing these early structural adaptations.
530 citations
TL;DR: It is suggested that global obesity and, to a greater extent, central obesity directly affect inflammation, which in turn negatively affects muscle strength, contributing to the development and progression of sarcopenic obesity.
Abstract: The aging process is often paralleled by decreases in muscle and increases in fat mass. At the extreme these two processes lead to a condition known as “sarcopenic obesity” (Roubenoff R. Ann NY Aca...
505 citations
TL;DR: The timing of the gene induction indicated early elevation of proteolytic genes, followed by prolonged elevation of cytokines and suppression of myostatin during and after an acute bout of resistance (RE) or run (RUN) exercise.
Abstract: The aim of this study was to examine the time course induction of select proteolytic [muscle ring finger-1 (MuRF-1), atrogin-1, forkhead box 3A (FOXO3A), calpain-1, calpain-2], myostatin, and cytok...
446 citations
TL;DR: An overview of muscle proteases, outline intracellular sources of reactive oxygen species, and summarize the evidence that connects oxidative stress to signaling pathways contributing to disuse muscle atrophy are provided.
Abstract: Skeletal muscle inactivity is associated with a loss of muscle protein and reduced force-generating capacity. This disuse-induced muscle atrophy results from both increased proteolysis and decreased protein synthesis. Investigations of the cell signaling pathways that regulate disuse muscle atrophy have increased our understanding of this complex process. Emerging evidence implicates oxidative stress as a key regulator of cell signaling pathways, leading to increased proteolysis and muscle atrophy during periods of prolonged disuse. This review will discuss the role of reactive oxygen species in the regulation of inactivity-induced skeletal muscle atrophy. The specific objectives of this article are to provide an overview of muscle proteases, outline intracellular sources of reactive oxygen species, and summarize the evidence that connects oxidative stress to signaling pathways contributing to disuse muscle atrophy. Moreover, this review will also discuss the specific role that oxidative stress plays in signaling pathways responsible for muscle proteolysis and myonuclear apoptosis and highlight gaps in our knowledge of disuse muscle atrophy. By presenting unresolved issues and suggesting topics for future research, it is hoped that this review will serve as a stimulus for the expansion of knowledge in this exciting field.
445 citations
TL;DR: The similar increase in fascicle length observed between the training groups mitigates against contraction mode being the predominant stimulus, and muscle architectural adaptations occur rapidly in response to resistance training but are strongly influenced by factors other than contraction mode.
Abstract: Studies using animal models have been unable to determine the mechanical stimuli that most influence muscle architectural adaptation. We examined the influence of contraction mode on muscle architectural change in humans, while also describing the time course of its adaptation through training and detraining. Twenty-one men and women performed slow-speed (30 degrees /s) concentric-only (Con) or eccentric-only (Ecc) isokinetic knee extensor training for 10 wk before completing a 3-mo detraining period. Fascicle length of the vastus lateralis (VL), measured by ultrasonography, increased similarly in both groups after 5 wk (Delta(Con) = +6.3 +/- 3.0%, Delta(Ecc) = +3.1 +/- 1.6%, mean = +4.7 +/- 1.7%; P < 0.05). No further increase was found at 10 wk, although a small increase (mean approximately 2.5%; not significant) was evident after detraining. Fascicle angle increased in both groups at 5 wk (Delta(Con) = +11.1 +/- 4.0%, Delta(Ecc) = +11.9 +/- 5.4%, mean = 11.5 +/- 3.2%; P < 0.05) and 10 wk (Delta(Con) = +13.3 +/- 3.0%, Delta(Ecc) = +21.4 +/- 6.9%, mean = 17.9 +/- 3.7%; P < 0.01) in VL only and remained above baseline after detraining (mean = 13.2%); smaller changes in vastus medialis did not reach significance. The similar increase in fascicle length observed between the training groups mitigates against contraction mode being the predominant stimulus. Our data are also strongly indicative of 1) a close association between VL fascicle length and shifts in the torque-angle relationship through training and detraining and 2) changes in fascicle angle being driven by space constraints in the hypertrophying muscle. Thus muscle architectural adaptations occur rapidly in response to resistance training but are strongly influenced by factors other than contraction mode.
443 citations
TL;DR: It is shown that seven sessions of HIIT over 2 wk induced marked increases in whole body and skeletal muscle capacity for fatty acid oxidation during exercise in moderately active women.
Abstract: Our aim was to examine the effects of seven high-intensity aerobic interval training (HIIT) sessions over 2 wk on skeletal muscle fuel content, mitochondrial enzyme activities, fatty acid transport...
426 citations
TL;DR: Results are the first to report alterations in expression of muscle-specific miRNAs in adult skeletal muscle and suggest miRNAAs may have a role in the adaptation to functional overload.
Abstract: MicroRNAs (miRNAs) are a class of highly conserved, noncoding RNAs involved in posttranscriptional gene regulation. A small number of muscle-specific miRNAs have been identified and shown to have a role in myoblast proliferation and differentiation as well as embryonic muscle growth. The primary objective of the present study was to determine the expression level of the muscle-specific miRNAs in the soleus and plantaris muscles and whether their expression in the plantaris was altered in response to functional overload. Of the miRNAs examined, only miRNA-206 was differentially expressed between soleus and plantaris muscles, as reflected by the sevenfold higher expression in the soleus for both the primary miRNA (pri-miRNA) and mature miRNA (miR). Following 7 days of functional overload, transcript levels for both pri-miRNA-1-2 and pri-miRNA-133a-2 increased by ∼2-fold, whereas pri-miRNA-206 levels were elevated 18.3-fold. In contrast, expression of miR-1 and miR-133a were downregulated by ∼50% following overload. The discrepancy between pri-miRNA and miR expression following overload was not explained by a change in the expression of components of the miRNA biogenesis pathway, since Drosha and Exportin-5 transcript levels were significantly increased by 50% in response to functional overload, whereas Dicer expression remained unchanged. These results are the first to report alterations in expression of muscle-specific miRNAs in adult skeletal muscle and suggest miRNAs may have a role in the adaptation to functional overload.
391 citations
TL;DR: Low-intensity resistance exercise training combined with blood flow restriction (REFR) increases muscle size and strength as much as conventional resistance exercise with high loads but without increasing the intensity of the exercise.
Abstract: Low-intensity resistance exercise training combined with blood flow restriction (REFR) increases muscle size and strength as much as conventional resistance exercise with high loads. However, the cellular mechanism(s) underlying the hypertrophy and strength gains induced by REFR are unknown. We have recently shown that both the mammalian target of rapamycin (mTOR) signaling pathway and muscle protein synthesis (MPS) were stimulated after an acute bout of high-intensity resistance exercise in humans. Therefore, we hypothesized that an acute bout of REFR would enhance mTOR signaling and stimulate MPS. We measured MPS and phosphorylation status of mTOR-associated signaling proteins in six young male subjects. Subjects were studied once during blood flow restriction (REFR, bilateral leg extension exercise at 20% of 1 repetition maximum while a pressure cuff was placed on the proximal end of both thighs and inflated at 200 mmHg) and a second time using the same exercise protocol but without the pressure cuff [control (Ctrl)]. MPS in the vastus lateralis muscle was measured by using stable isotope techniques, and the phosphorylation status of signaling proteins was determined by immunoblotting. Blood lactate, cortisol, and growth hormone were higher following REFR compared with Ctrl (P < 0.05). Ribosomal S6 kinase 1 (S6K1) phosphorylation, a downstream target of mTOR, increased concurrently with a decreased eukaryotic translation elongation factor 2 (eEF2) phosphorylation and a 46% increase in MPS following REFR (P < 0.05). MPS and S6K1 phosphorylation were unchanged in the Ctrl group postexercise. We conclude that the activation of the mTOR signaling pathway appears to be an important cellular mechanism that may help explain the enhanced muscle protein synthesis during REFR.
384 citations
TL;DR: Drawing general conclusions that hypoxia-induced ROS may be a normal physiological response to imbalance in oxygen supply and demand or environmental stress and may play a yet undefined role in normal response mechanisms to these stimuli are drawn.
Abstract: The existence of hypoxia-induced reactive oxygen species (ROS) production remains controversial. However, numerous observations with a variety of methods and in many cells and tissue types are supp...
TL;DR: Glycation-related cross-linking of intramuscular connective tissue may contribute to altered muscle force transmission and muscle function with healthy aging.
Abstract: We examined intramuscular endomysial collagen, cross-linking, and advanced glycation end products, as well as the general and contractile protein concentration of 20 young (25 +/- 3 yr) and 22 old (78 +/- 6 yr, range: 70-93 yr) sedentary men and women to better understand the underlying basis of changes in skeletal muscle mass and function that occur with aging. The old individuals had an impaired ability (increased time) (P 0.05) with aging. The advanced glycation end product, pentosidine, was increased (P 0.05) with aging. These data suggest that the synthesis and degradation of proteins responsible for the generation (myosin and actin) and transfer (collagen and pyridinoline cross-links) of muscle force are tightly regulated in aging muscle. Glycation-related cross-linking of intramuscular connective tissue may contribute to altered muscle force transmission and muscle function with healthy aging.
TL;DR: Two major regulators of gene transcription and metabolism in response to oxidative, energetic, and mechanical stress in skeletal muscle are studied.
Abstract: Mitogen-activated protein kinases (MAPKs) and NF-κB are two major regulators of gene transcription and metabolism in response to oxidative, energetic, and mechanical stress in skeletal muscle. Chro...
TL;DR: It is concluded that the shear stimulus AUC, not the peak itself, is the critical determinant of the peak FMD response, indicating AUC as the best method of quantifying reactive hyperemiaShear stimulus for %FMD normalization.
Abstract: We investigated the independent contributions of the peak and continued reactive hyperemia on flow-mediated dilation (FMD). 1) For the duration manipulation experiment (DME), 10 healthy males exper...
TL;DR: Proton MRS can be used to noninvasively quantify human muscle Carnosine content and muscle carnosine is increased by oral beta-alanine supplementation in sprint-trained athletes; carnosinesine loading slightly but significantly attenuated fatigue in repeated bouts of exhaustive dynamic contractions; and the increase in muscle Carnival did not improve isometric endurance or 400-m race time.
Abstract: Carnosine (β-alanyl-l-histidine) is present in high concentrations in human skeletal muscle. The ingestion of β-alanine, the rate-limiting precursor of carnosine, has been shown to elevate the musc...
TL;DR: A substantial proportion of the between-individual variance in relationships between PAI, accelerometry, and HR is captured with simple calibration procedures, feasible for use in epidemiological studies.
Abstract: Combining accelerometry with heart rate (HR) monitoring may improve precision of physical activity measurement. Considerable variation exists in the relationships between physical activity intensity (PAI) and HR and accelerometry, which may be reduced by individual calibration. However, individual calibration limits feasibility of these techniques in population studies, and less burdensome, yet valid, methods of calibration are required. We aimed to evaluate the precision of different individual calibration procedures against a reference calibration procedure: a ramped treadmill walking-running test with continuous measurement of PAI by indirect calorimetry in 26 women and 25 men [mean (SD): 35 (9) yr, 1.69 (0.10) m, 70 (14) kg]. Acceleration (along the longitudinal axis of the trunk) and HR were measured simultaneously. Alternative calibration procedures included treadmill testing without calorimetry, submaximal step and walk tests with and without calorimetry, and nonexercise calibration using sleeping HR and gender. Reference accelerometry and HR models explained >95% of the between-individual variance in PAI (P < 0.001). This fraction dropped to 73 and 81%, respectively, for accelerometry and HR models calibrated with treadmill tests without calorimetry. Step-test calibration captured 62-64% (accelerometry) and 68% (HR) of the variance between individuals. Corresponding values were 63-76% and 59-61% for walk-test calibration. There was only little benefit of including calorimetry during step and walk calibration for HR models. Nonexercise calibration procedures explained 54% (accelerometry) and 30% (HR) of the between-individual variance. In conclusion, a substantial proportion of the between-individual variance in relationships between PAI, accelerometry, and HR is captured with simple calibration procedures, feasible for use in epidemiological studies.
TL;DR: It is concluded that both area- and length- based measurements can be used to determine relative infarct size over a wide range of severity, although the area-based measurements are substantially more compressed due to wall thinning, and that the estimation ofinfarct midlines is a simple, reliable approach to infarCT size assessment.
Abstract: Efficacy of potential treatments for myocardial infarction (MI) is commonly assessed by histological measurement of infarct size in rodent models. In experiments involving an acute MI setting, meas...
TL;DR: It is demonstrated that plasma acylated ghrelin concentration and hunger are suppressed during running.
Abstract: Ghrelin is an orexigenic hormone secreted from endocrine cells in the stomach and other tissues. Acylation of ghrelin is essential for appetite regulation. Vigorous exercise induces appetite suppre...
TL;DR: It is unlikely that changes in cerebral oxygenation limit incremental exercise performance in normoxia, yet it is possible that such changes play a more pivotal role in hypoxia.
Abstract: To determine if fatigue at maximal aerobic power output was associated with a critical decrease in cerebral oxygenation, 13 male cyclists performed incremental maximal exercise tests (25 W/min ramp...
TL;DR: It is suggested that increased mechanical loads and blunted neuromuscular responses are both required for the development of obstructive sleep apnea.
Abstract: Obstructive sleep apnea is caused by pharyngeal occlusion due to alterations in upper airway mechanical properties and/or disturbances in neuromuscular control. The objective of the study was to de...
TL;DR: The high-amount group had significant improvements in high-density lipoprotein (HDL)-cholesterol, HDL particle size, and large HDL levels that were sustained for 15 days after exercise stopped, compared with the other groups.
Abstract: Exercise has beneficial effects on lipoproteins. Little is known about how long the effects persist with detraining or whether the duration of benefit is effected by training intensity or amount. S...
TL;DR: The pitfalls of lung morphometry are discussed and solutions, from specimen preparation to the sampling scheme in multiple stages, are presented for obtaining unbiased estimates of morphometric parameters such as volumes, surfaces, lengths, and numbers.
Abstract: Quantitative data on lung structure are essential to set up structure-function models for assessing the functional performance of the lung or to make statistically valid comparisons in experimental morphology, physiology, or pathology. The methods of choice for microscopy-based lung morphometry are those of stereology, the science of quantitative characterization of irregular three-dimensional objects on the basis of measurements made on two-dimensional sections. From a practical perspective, stereology is an assumption-free set of methods of unbiased sampling with geometric probes, based on a solid mathematical foundation. Here, we discuss the pitfalls of lung morphometry and present solutions, from specimen preparation to the sampling scheme in multiple stages, for obtaining unbiased estimates of morphometric parameters such as volumes, surfaces, lengths, and numbers. This is demonstrated on various examples. Stereological methods are accurate, efficient, simple, and transparent; the precision of the estimates depends on the size and distribution of the sample. For obtaining quantitative data on lung structure at all microscopic levels, state-of-the-art stereology is the gold standard.
TL;DR: It is concluded that chronic intermittent hypoxia leads to hypercholesterolemia and lipid peroxidation in the absence of obesity, and the degree of metabolic dysregulation is dependent on the severity of the hypoxic stimulus.
Abstract: Obstructive sleep apnea (OSA) is characterized by chronic intermittent hypoxia (CIH) and associated with dysregulation of lipid metabolisms and atherosclerosis. Causal relationships between OSA and...
TL;DR: Results suggest that increases in MVC observed in the first few days of isometric resistance training can be accounted for by an increase in the rate of activation at the onset of muscle contraction.
Abstract: This study employed longitudinal measures of evoked spinal reflex responses (Hoffman reflex, V wave) to investigate changes in the activation of muscle and to determine if there are “linked” neural...
TL;DR: Endogenous H(2)S was cardioprotective in the rat model of MI and cystathionine-gamma-lyase protein localization in the myocardium of the infarct area was shown for the first time by using immunohistochemical staining.
Abstract: The role of hydrogen sulfide (H2S) in myocardial infarction (MI) has not been previously studied. We therefore investigated the effect of H2S in a rat model of MI in vivo. Animals were randomly div...
TL;DR: Current knowledge supports the likelihood that interactions between the primary genetic defect and disruptions in the normal production of free radicals contribute to the pathophysiology of muscular dystrophies.
Abstract: Null mutation of any one of several members of the dystrophin protein complex can cause progressive, and possibly fatal, muscle wasting. Although these muscular dystrophies arise from mutation of a single gene that is expressed primarily in muscle, the resulting pathology is complex and multisystemic, which shows a broader disruption of homeostasis than would be predicted by deletion of a single-gene product. Before the identification of the deficient proteins that underlie muscular dystrophies, such as Duchenne muscular dystrophy (DMD), oxidative stress was proposed as a major cause of the disease. Now, current knowledge supports the likelihood that interactions between the primary genetic defect and disruptions in the normal production of free radicals contribute to the pathophysiology of muscular dystrophies. In this review, we focus on the pathophysiology that results from dystrophin deficiency in humans with DMD and the mdx mouse model of DMD. Current evidence indicates three general routes through which free radical production can be disrupted in dystrophin deficiency to contribute to the ensuing pathology. First, constitutive differences in free radical production can disrupt signaling processes in muscle and other tissues and thereby exacerbate pathology. Second, tissue responses to the presence of pathology can cause a shift in free radical production that can promote cellular injury and dysfunction. Finally, behavioral differences in the affected individual can cause further changes in the production and stoichiometry of free radicals and thereby contribute to disease. Unfortunately, the complexity of the free radical-mediated processes that are perturbed in complex pathologies such as DMD will make it difficult to develop therapeutic approaches founded on systemic administration of antioxidants. More mechanistic knowledge of the specific disruptions of free radicals that underlie major features of muscular dystrophy is needed to develop more targeted and successful therapeutic approaches.
TL;DR: It is illustrated that, despite the reduced mitochondrial content, denervated muscle has greater mitochondrial apoptotic susceptibility, which coincided with elevated apoptosis, and these processes may contribute to denervation-induced muscle atrophy.
Abstract: Chronic muscle disuse induced by denervation reduces mitochondrial content and produces muscle atrophy. To investigate the molecular mechanisms responsible for these adaptations, we assessed 1) mit...
TL;DR: Evaluation of the factors regulating these processes and the functions of the reactive oxygen species generated are important in understanding the redox biology of skeletal muscle.
Abstract: Skeletal muscle has been recognized as a potential source for generation of reactive oxygen and nitrogen species for more than 20 years. Initial investigations concentrated on the potential role of mitochondria as a major source for generation of superoxide as a "by-product" of normal oxidative metabolism, but recent studies have identified multiple subcellular sites, where superoxide or nitric oxide are generated in regulated and controlled systems in response to cellular stimuli. Full evaluation of the factors regulating these processes and the functions of the reactive oxygen species generated are important in understanding the redox biology of skeletal muscle.
TL;DR: In vivo variations in regional lung density affect the interpretation of vertical gradients in pulmonary blood flow and is consistent with a simple conceptual model: the lung behaves like a Slinky, a deformable spring distorting under its own weight.
Abstract: In vivo radioactive tracer and microsphere studies have differing conclusions as to the magnitude of the gravitational effect on the distribution of pulmonary blood flow. We hypothesized that some ...
TL;DR: Correct ApEn, SampEn, and CCE provide global indices that can be helpful to monitor sympathovagal balance and evidence a progressive decrease of complexity as a function of the tilt table inclination, indicating that complexity is under control of the autonomic nervous system.
Abstract: Complexity (or its opposite, regularity) of heart period variability has been related to age and disease but never linked to a progressive shift of the sympathovagal balance. We compare several wel...