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Showing papers in "Journal of Applied Physiology in 2005"


Journal ArticleDOI
TL;DR: It is suggested that myokines may be involved in mediating the health-beneficial effects of exercise and that these in particular are involved in the protection against chronic diseases associated with low-grade inflammation such as diabetes and cardiovascular diseases.
Abstract: Regular exercise offers protection against all-cause mortality, primarily by protection against cardiovascular disease and Type 2 diabetes mellitus. The latter disorders have been associated with chronic low-grade systemic inflammation reflected by a two- to threefold elevated level of several cytokines. Adipose tissue contributes to the production of TNF-alpha, which is reflected by elevated levels of soluble TNF-alpha receptors, IL-6, IL-1 receptor antagonist, and C-reactive protein. We suggest that TNF-alpha rather than IL-6 is the driver behind insulin resistance and dyslipidemia and that IL-6 is a marker of the metabolic syndrome, rather than a cause. During exercise, IL-6 is produced by muscle fibers via a TNF-independent pathway. IL-6 stimulates the appearance in the circulation of other anti-inflammatory cytokines such as IL-1ra and IL-10 and inhibits the production of the proinflammatory cytokine TNF-alpha. In addition, IL-6 enhances lipid turnover, stimulating lipolysis as well as fat oxidation. We suggest that regular exercise induces suppression of TNF-alpha and thereby offers protection against TNF-alpha-induced insulin resistance. Recently, IL-6 was introduced as the first myokine, defined as a cytokine that is produced and released by contracting skeletal muscle fibers, exerting its effects in other organs of the body. Here we suggest that myokines may be involved in mediating the health-beneficial effects of exercise and that these in particular are involved in the protection against chronic diseases associated with low-grade inflammation such as diabetes and cardiovascular diseases.

2,659 citations


Journal ArticleDOI
TL;DR: Chronic sleep loss, behavioral or sleep disorder related, may represent a novel risk factor for weight gain, insulin resistance, and Type 2 diabetes.
Abstract: Chronic sleep loss as a consequence of voluntary bedtime restriction is an endemic condition in modern society. Although sleep exerts marked modulatory effects on glucose metabolism, and molecular mechanisms for the interaction between sleeping and feeding have been documented, the potential impact of recurrent sleep curtailment on the risk for diabetes and obesity has only recently been investigated. In laboratory studies of healthy young adults submitted to recurrent partial sleep restriction, marked alterations in glucose metabolism including decreased glucose tolerance and insulin sensitivity have been demonstrated. The neuroendocrine regulation of appetite was also affected as the levels of the anorexigenic hormone leptin were decreased, whereas the levels of the orexigenic factor ghrelin were increased. Importantly, these neuroendocrine abnormalities were correlated with increased hunger and appetite, which may lead to overeating and weight gain. Consistent with these laboratory findings, a growing body of epidemiological evidence supports an association between short sleep duration and the risk for obesity and diabetes. Chronic sleep loss may also be the consequence of pathological conditions such as sleep-disordered breathing. In this increasingly prevalent syndrome, a feedforward cascade of negative events generated by sleep loss, sleep fragmentation, and hypoxia are likely to exacerbate the severity of metabolic disturbances. In conclusion, chronic sleep loss, behavioral or sleep disorder related, may represent a novel risk factor for weight gain, insulin resistance, and Type 2 diabetes.

1,090 citations


Journal ArticleDOI
TL;DR: It is concluded that short sprint interval training (approximately 15 min of intense exercise over 2 wk) increased muscle oxidative potential and doubled endurance capacity during intense aerobic cycling in recreationally active individuals.
Abstract: Parra et al. (Acta Physiol. Scand 169: 157–165, 2000) showed that 2 wk of daily sprint interval training (SIT) increased citrate synthase (CS) maximal activity but did not change “anaerobic” work c...

811 citations


Journal ArticleDOI
TL;DR: Public health initiatives promoting moderate increases in physical activity may offer the best balance between efficacy and feasibility to improve metabolic and cardiovascular health in largely sedentary populations.
Abstract: Epidemiological studies suggest that physically active individuals have a 30-50% lower risk of developing type 2 diabetes than do sedentary persons and that physical activity confers a similar risk reduction for coronary heart disease. Risk reductions are observed with as little as 30 min of moderate-intensity activity per day. Protective mechanisms of physical activity include the regulation of body weight; the reduction of insulin resistance, hypertension, atherogenic dyslipidemia, and inflammation; and the enhancement of insulin sensitivity, glycemic control, and fibrinolytic and endothelial function. Public health initiatives promoting moderate increases in physical activity may offer the best balance between efficacy and feasibility to improve metabolic and cardiovascular health in largely sedentary populations.

752 citations


Journal ArticleDOI
TL;DR: If the expanding epidemic of obesity seen in the United States continues, the prevalence of SDB will almost certainly increase, along with the proportion ofSDB attributable to obesity.
Abstract: Excess weight is a well-established predictor of sleep-disordered breathing (SDB). Clinical observations and population studies throughout the United States, Europe, Asia, and Australia have consis...

723 citations


Journal ArticleDOI
TL;DR: In conclusion, the described microanalytical technique enables continuous sampling of extremely small quantities of substances directly from soft tissue, with minimal system perturbation and without harmful effects on subjects.
Abstract: Myofascial pain associated with myofascial trigger points (MTrPs) is a common cause of nonarticular musculoskeletal pain. Although the presence of MTrPs can be determined by soft tissue palpation, ...

568 citations


Journal ArticleDOI
TL;DR: The effects of exercise and diet in the prevention of chronic disease are discussed, the effects of lifestyle modification for both mitigating disease progression and reversing existing disease are highlighted, and potential mechanisms for beneficial effects are suggested.
Abstract: Currently, modern chronic diseases, including cardiovascular diseases, Type 2 diabetes, metabolic syndrome, and cancer, are the leading killers in Westernized society and are increasing rampantly in developing nations. In fact, obesity, diabetes, and hypertension are now even commonplace in children. Clearly, however, there is a solution to this epidemic of metabolic disease that is inundating today's societies worldwide: exercise and diet. Overwhelming evidence from a variety of sources, including epidemiological, prospective cohort, and intervention studies, links most chronic diseases seen in the world today to physical inactivity and inappropriate diet consumption. The purpose of this review is to 1) discuss the effects of exercise and diet in the prevention of chronic disease, 2) highlight the effects of lifestyle modification for both mitigating disease progression and reversing existing disease, and 3) suggest potential mechanisms for beneficial effects.

563 citations


Journal ArticleDOI
TL;DR: The specificity of cell response to stiffness and how this may be important in particular tissue systems is discussed and the mechanoresponse to real pathological states is linked and speculated on the possible biological significance of mechanosensing.
Abstract: Many cell types respond to forces as acutely as they do to chemical stimuli, but the mechanisms by which cells sense mechanical stimuli and how these factors alter cellular structure and function i...

524 citations


Journal ArticleDOI
TL;DR: The changes seen in the IL-6-infused muscles suggest alterations in the balance of growth factor-related signaling in favor of a more catabolic profile, which suggests that downregulation ofgrowth factor-mediated intracellular signaling may be a mechanism contributing to the development of muscle atrophy induced by elevated IL- 6.
Abstract: Chronic, low-level elevation of circulating interleukin (IL)-6 is observed in disease states as well as in many outwardly healthy elderly individuals. Increased plasma IL-6 is also observed after intense, prolonged exercise. In the context of skeletal muscle, IL-6 has variously been reported to regulate carbohydrate and lipid metabolism, increase satellite cell proliferation, or cause muscle wasting. In the present study, we used a rodent local infusion model to deliver modest levels of IL-6, comparable to that present after exercise or with chronic low-level inflammation in the elderly, directly into a single target muscle in vivo. The aim of this study was to examine the direct effects of IL-6 on skeletal muscle in the absence of systemic changes in this cytokine. Data included cellular and molecular markers of cytokine and growth factor signaling (phosphorylation and mRNA content) as well as measurements to detect muscle atrophy. IL-6 infusion resulted in muscle atrophy characterized by a preferential loss of myofibrillar protein (-17%). IL-6 induced a decrease in the phosphorylation of ribosomal S6 kinase (-60%) and STAT5 (-33%), whereas that of STAT3 was increased approximately twofold. The changes seen in the IL-6-infused muscles suggest alterations in the balance of growth factor-related signaling in favor of a more catabolic profile. This suggests that downregulation of growth factor-mediated intracellular signaling may be a mechanism contributing to the development of muscle atrophy induced by elevated IL-6.

522 citations


Journal ArticleDOI
TL;DR: Body surface area was found to be a more important determinant of the size of each of the cardiovascular structures than age, height, or weight alone and fit a complex model predicted by the nonlinear decrease of heart rate with growth.
Abstract: Basic fluid dynamic principles were used to derive a theoretical model of optimum cardiovascular allometry, the relationship between somatic and cardiovascular growth. The validity of the predicted models was then tested against the size of 22 cardiovascular structures measured echocardiographically in 496 normal children aged 1 day to 20 yr, including valves, pulmonary arteries, aorta and aortic branches, pulmonary veins, and left ventricular volume. Body surface area (BSA) was found to be a more important determinant of the size of each of the cardiovascular structures than age, height, or weight alone. The observed vascular and valvar dimensions were in agreement with values predicted from the theoretical models. Vascular and valve diameters related linearly to the square root of BSA, whereas valve and vascular areas related to BSA. The relationship between left ventricular volume and body size fit a complex model predicted by the nonlinear decrease of heart rate with growth. Overall, the relationship between cardiac output and body size is the fundamental driving factor in cardiovascular allometry.

463 citations


Journal ArticleDOI
TL;DR: The effect of exercise on muscle insulin sensitivity is mimicked by hypoxia and by treatment of muscles with 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside to activate AMP-activated protein kinase.
Abstract: Exercise/muscle contraction activates glucose transport. The increase in muscle glucose transport induced by exercise is independent of insulin. As the acute effect of exercise on glucose transport...

Journal ArticleDOI
TL;DR: Data indicate that muscle output in high-force isometric and dynamic muscle actions is positively related to the stiffness of the tendinous structures, possibly by means of a more effective force transmission from the contractile elements to the bone.
Abstract: Contractile force is transmitted to the skeleton through tendons and aponeuroses, and, although it is appreciated that the mechanocharacteristics of these tissues play an important role for movement performance with respect to energy storage, the association between tendon mechanical properties and the contractile muscle output during high-force movement tasks remains elusive. The purpose of the study was to investigate the relation between the mechanical properties of the connective tissue and muscle performance in maximal isometric and dynamic muscle actions. Sixteen trained men participated in the study. The mechanical properties of the vastus lateralis tendon-aponeurosis complex were assessed by ultrasonography. Maximal isometric knee extensor force and rate of torque development (RTD) were determined. Dynamic performance was assessed by maximal squat jumps and countermovement jumps on a force plate. From the vertical ground reaction force, maximal jump height, jump power, and force-/velocity-related determinants of jump performance were obtained. RTD was positively related to the stiffness of the tendinous structures (r = 0.55, P < 0.05), indicating that tendon mechanical properties may account for up to 30% of the variance in RTD. A correlation was observed between stiffness and maximal jump height in squat jumps and countermovement jumps (r = 0.64, P < 0.05 and r = 0.55, P < 0.05). Power, force, and velocity parameters obtained during the jumps were significantly correlated to tendon stiffness. These data indicate that muscle output in high-force isometric and dynamic muscle actions is positively related to the stiffness of the tendinous structures, possibly by means of a more effective force transmission from the contractile elements to the bone.

Journal ArticleDOI
TL;DR: The Redox Theory for the mechanism of HPV proposes the coordinated action of a redox sensor (the proximal mitochondrial electron transport chain) that generates a diffusible mediator [a reactive O(2) species (ROS)] that regulates an effector protein [voltage-gated potassium (K(v) and calcium channels].
Abstract: Humans encounter hypoxia throughout their lives. This occurs by destiny in utero, through disease, and by desire, in our quest for altitude. Hypoxic pulmonary vasoconstriction (HPV) is a widely con...

Journal ArticleDOI
TL;DR: The metabolic equivalent (MET) is a physiological concept that represents a simple procedure for expressing energy cost of physical activities as multiples of resting metabolic rate (RM) as discussed by the authors, which is a common physiological concept.
Abstract: The metabolic equivalent (MET) is a widely used physiological concept that represents a simple procedure for expressing energy cost of physical activities as multiples of resting metabolic rate (RM...

Journal ArticleDOI
TL;DR: It was hypothesised that exercise intensity is of primary importance to the regulation of fat oxidation and that gender, body composition, physical activity level, and training status are secondary and can explain part of the observed interindividual variation.
Abstract: The aim of the present study was to establish fat oxidation rates over a range of exercise intensities in a large group of healthy men and women. It was hypothesised that exercise intensity is of p...

Journal ArticleDOI
TL;DR: The findings suggest that the elastic recoil takes place not as a spring-like bouncing but as a catapult action in natural human walking.
Abstract: The present study was designed to explore how the interaction between the fascicles and tendinous tissues is involved in storage and utilization of elastic energy during human walking. Eight male subjects walked with a natural cadence (1.4 ± 0.1 m/s) on a 10-m-long force plate system. In vivo techniques were employed to record the Achilles tendon force and to scan real-time fascicle lengths for two muscles (medial gastrocnemius and soleus). The results showed that tendinous tissues of both medial gastrocnemius and soleus muscles lengthened slowly throughout the single-stance phase and then recoiled rapidly close to the end of the ground contact. However, the fascicle length changes demonstrated different patterns and amplitudes between two muscles. The medial gastrocnemius fascicles were stretched during the early single-stance phase and then remained isometrically during the late-stance phase. In contrast, the soleus fascicles were lengthened until the end of the single-stance phase. These findings suggest that the elastic recoil takes place not as a spring-like bouncing but as a catapult action in natural human walking. The interaction between the muscle fascicles and tendinous tissues plays an important role in the process of release of elastic energy, although the leg muscles, which are commonly accepted as synergists, do not have similar mechanical behavior of fascicles in this catapult action.

Journal ArticleDOI
TL;DR: In summary, acute SD was associated with increased sympathetic and decreased parasympathetic cardiovascular modulation and decreased BRS, most consistently in the seated position and during simple reaction-time testing.
Abstract: Cardiovascular autonomic modulation during 36 h of total sleep deprivation (SD) was assessed in 18 normal subjects (16 men, 2 women, 26.0 ± 4.6 yr old). ECG and continuous blood pressure (BP) from ...

Journal ArticleDOI
TL;DR: The data show that increased corticospinal excitability may develop over several weeks of skill training and indicate that these changes may be of importance for task acquisition and that different adaptive changes are involved in neural adaptation to strength training.
Abstract: Changes in corticospinal excitability induced by 4 wk of heavy strength training or visuomotor skill learning were investigated in 24 healthy human subjects. Measurements of the input-output relati...

Journal ArticleDOI
TL;DR: The results indicate the amount of amplitude cancellation that can occur in various experimental conditions and its influence on absolute and relative measures of EMG amplitude.
Abstract: The purpose of the study was to quantify the influence of selected motor unit properties and patterns of activity on amplitude cancellation in the simulated surface electromyogram (EMG). The study ...

Journal ArticleDOI
TL;DR: The available data suggest that sleep apnea is independently associated with altered glucose metabolism and may predispose to the eventual development of Type 2 diabetes mellitus, and the cause-and-effect relationship remains to be determined.
Abstract: Sleep is a complex behavioral state that occupies one-third of the human life span. Although viewed as a passive condition, sleep is a highly active and dynamic process. The sleep-related decrease ...

Journal ArticleDOI
TL;DR: The hypothesis is that the most proximal behavioral cause of insulin resistance is physical inactivity, and several streams of scientific research have demonstrated a role for physical activity in the etiology and prevention of diabetes and its related morbidity.
Abstract: Diabetes has reached epidemic proportions worldwide and is associated with a large economic burden, increased risk of cardiovascular disease, and premature mortality. Hyperglycemia is the hallmark clinical manifestation of diabetes and evolves through a multifactorial etiology of genetic, environmental, and behavioral enablers. Approximately 90% of diabetes cases are the non-insulin-dependent phenotype, which is characterized by a progressive deterioration in insulin-mediated glucose disposal, particularly by peripheral tissues. Our hypothesis is that the most proximal behavioral cause of insulin resistance is physical inactivity. Indeed, several streams of scientific research have demonstrated a role for physical activity in the etiology and prevention of diabetes and its related morbidity. In this review we will discuss some of the key observational and experimental studies that have examined associations among physical activity, cardiorespiratory fitness, and non-insulin-dependent diabetes.

Journal ArticleDOI
TL;DR: Regular exercise without weight loss is associated with a substantial reduction in total and visceral fat and in skeletal muscle lipid in both obesity and T2D.
Abstract: It is unclear whether chronic exercise without caloric restriction or weight loss is a useful strategy for obesity reduction in obese men with and without Type 2 diabetes (T2D). We examined the eff...

Journal ArticleDOI
TL;DR: These studies confirm in humans that high capillary pressure induces a high-permeability-type lung edema in the absence of inflammation, a concept first introduced under the term "stress failure."
Abstract: High-altitude pulmonary edema (HAPE) develops in rapidly ascending nonacclimatized healthy individuals at altitudes above 3,000 m. An excessive rise in pulmonary artery pressure (PAP) preceding ede...

Journal ArticleDOI
TL;DR: The pathogenesis of obstructive sleep apnea has been under investigation for over 25 years, during which a number of factors that contribute to upper airway collapse during sleep have been identified and suggests that OSA may be a heterogeneous disorder, rather than a single disease entity.
Abstract: The pathogenesis of obstructive sleep apnea (OSA) has been under investigation for over 25 years, during which a number of factors that contribute to upper airway (UA) collapse during sleep have been identified. Structural/anatomic factors that constrict space for the soft tissues surrounding the pharynx and its lumen are crucial to the development of OSA in many patients. Enlargement of soft tissues enveloping the pharynx, including hypertrophied tonsils, adenoids, and tongue, is also an important factor predisposing to UA collapse, inasmuch as this can impinge on the pharyngeal lumen and narrow it during sleep. Other factors, including impairment of UA mechanoreceptor sensitivity and reflexes that maintain pharyngeal patency and respiratory control system instability, have also been identified as possible mechanisms facilitating UA instability. This suggests that OSA may be a heterogeneous disorder, rather than a single disease entity. Therefore, the extent to which various pathogenic factors contribute to the phenomenon of repetitive collapse of the UA during sleep probably varies from patient to patient. Further elucidation of specific pathogenic mechanisms in individuals with OSA may facilitate the development of new therapies that can be tailored to individual patient needs according to the underlying mechanism(s) of their disease.

Journal ArticleDOI
TL;DR: Associations between ACTN3 genotype and muscle size and elbow flexor isometric and dynamic strength in a large group of men and women enrolled in a 12-wk standardized elbowflexor/extensor resistance training program of the nondominant arm were studied.
Abstract: The α-actinin 3 (ACTN3) gene encodes a protein of the Z disk of myofibers, and a polymorphism of ACTN3 results in complete loss of the protein. The ACTN3 genotype (R577X) has been found to be assoc...

Journal ArticleDOI
TL;DR: Recent studies in transgenic and knockout animals show that AMP-activated protein kinase is not the sole mediator of the signal to GLUT4 translocation and suggest that there may be redundant signaling pathways leading to contraction-stimulated glucose transport.
Abstract: Contracting skeletal muscles acutely increases glucose transport in both healthy individuals and in people with Type 2 diabetes, and regular physical exercise is a cornerstone in the treatment of the disease. Glucose transport in skeletal muscle is dependent on the translocation of GLUT4 glucose transporters to the cell surface. It has long been believed that there are two major signaling mechanisms leading to GLUT4 translocation. One mechanism is insulin-activated signaling through insulin receptor substrate-1 and phosphatidylinositol 3-kinase. The other is an insulin-independent signaling mechanism that is activated by contractions, but the mediators of this signal are still unknown. Accumulating evidence suggests that the energy-sensing enzyme AMP-activated protein kinase plays an important role in contraction-stimulated glucose transport. However, more recent studies in transgenic and knockout animals show that AMP-activated protein kinase is not the sole mediator of the signal to GLUT4 translocation and suggest that there may be redundant signaling pathways leading to contraction-stimulated glucose transport. The search for other possible signal intermediates is ongoing, and calcium, nitric oxide, bradykinin, and the Akt substrate AS160 have been suggested as possible candidates. Further research is needed because full elucidation of an insulin-independent signal leading to glucose transport would be a promising pharmacological target for the treatment of Type 2 diabetes.

Journal ArticleDOI
TL;DR: There is agreement about the need for high levels of physical activity to maintain weight loss, but there is a need for more research to understand why physical activity is critical for weight loss maintenance.
Abstract: There is an inverse relationship between physical activity and weight gain. However, additional research is needed to quantify the amount of physical activity required to prevent weight gain in different populations, improve the way we convey physical activity recommendations to the public, and help the individuals increase their physical activity. Although physical activity does not appear to contribute significantly to weight loss, it is critical for maintenance of weight loss. Available data are consistent in that 60-90 min/day of moderate-intensity physical activity is required to maintain a significant weight loss. Although there is agreement about the need for high levels of physical activity to maintain weight loss, there is a need for more research to understand why physical activity is critical for weight loss maintenance. Finally, additional research is needed to determine whether there is an optimal level of physical activity below which it is difficult for most people to achieve a balance between energy intake and expenditure at a healthy body weight. The increasing prevalence of obesity may reflect the fact that the majority of the population has fallen below such a level of physical activity.

Journal ArticleDOI
TL;DR: A modest exercise program, consistent with recommendations from the Centers for Disease Control/American College of Sports Medicine (CDC/ACSM), prevented significant increases in visceral fat and subcutaneous and total abdominal fat without changes in caloric intake.
Abstract: Despite the importance of randomized, dose-response studies for proper evaluation of effective clinical interventions, there have been no dose-response studies on the effects of exercise amount on ...

Journal ArticleDOI
TL;DR: It is concluded that fibrin-based gels provide a novel method to engineer three-dimensional functional muscle tissue and that these tissues may be used to model the development of skeletal muscle in vitro.
Abstract: The transition of a muscle cell from a differentiated myotube into an adult myofiber is largely unstudied. This is primarily due to the difficulty of isolating specific developmental stimuli in vivo and the inability to maintain viable myotubes in culture for sufficient lengths of time. To address these limitations, a novel method for rapidly generating three-dimensional engineered muscles using fibrin gel casting has been developed. Myoblasts were seeded and differentiated on top of a fibrin gel. Cell-mediated contraction of the gel around artificial anchors placed 12 mm apart culminates 10 days after plating in a tubular structure of small myotubes (10-μm diameter) surrounded by a fibrin gel matrix. These tissues can be connected to a force transducer and electrically stimulated between parallel platinum electrodes to monitor physiological function. Three weeks after plating, the three-dimensional engineered muscle generated a maximum twitch force of 329 ± 26.3 μN and a maximal tetanic force of 805.8 ± 55 μN. The engineered muscles demonstrated normal physiological function including length-tension and force-frequency relationships. Treatment with IGF-I resulted in a 50% increase in force production, demonstrating that these muscles responded to hormonal interventions. Although the force production was maximal at 3 wk, constructs can be maintained in culture for up to 6 wk with no intervention. We conclude that fibrin-based gels provide a novel method to engineer three-dimensional functional muscle tissue and that these tissues may be used to model the development of skeletal muscle in vitro.

Journal ArticleDOI
TL;DR: Data indicate a myogenic and metabolic gene induction with RE and Run exercise and provides basic information for the timing of human muscle biopsy samples for gene-expression studies involving exercise.
Abstract: The aim of this study was to examine the time course activation of select myogenic (MRF4, Myf5, MyoD, myogenin) and metabolic (CD36, CPT1, HKII, and PDK4) genes after an acute bout of resistance (R...