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The continuous dynamic reshaping of mitochondria by fusion and fission events is critical to keep mitochondrial quality and function under control in response to changes in energy and stress. Maintaining a functional, highly interconnected mitochondrial reticulum ensures rapid energy production and distribution. Moreover, mitochondrial networks act as dynamic signaling hub to adapt to the metabolic demands imposed by contraction, energy expenditure, and general metabolism. However, excessive mitochondrial fusion or fission results in the disruption of the skeletal muscle mitochondrial network integrity and activates a retrograde response from mitochondria to the nucleus, leading to muscle atrophy, weakness and influencing whole-body homeostasis. These actions are mediated via the secretion of mitochondrial-stress myokines such as FGF21 and GDF15. Here we will summarize recent discoveries in the role of mitochondrial fusion and fission in the control of muscle mass and in regulating physiological homeostasis and disease progression.
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Mitocôndrias Musculares , Dinâmica Mitocondrial , Músculo Esquelético , Músculo Esquelético/metabolismo , Mitocôndrias Musculares/fisiologia , HumanosRESUMO
Myokines, released from the muscle, enable communication between the working muscles and other tissues. Their release during physical exercise is assumed to depend on immune-hormonal-metabolic interactions concerning mode (endurance or resistance exercise), duration, and intensity. This meta-analysis aims to examine the acute changes of circulating myokines inducing immunoregulatory effects caused by a bout of resistance exercise and to consider potential moderators of the results. Based on this selection strategy, a systematic literature search was conducted for resistance exercise intervention studies measuring interleukin (IL-) 6, IL-10, IL-1ra, tumor necrosis factor (TNF-) α, IL-15, IL-7, transforming growth factor (TGF-) ß1, and fractalkines (FKN) before and immediately after resistance exercise in healthy individuals. Random-effects meta-analysis was performed for each myokine. We identified a moderate positive effect of resistance exercise for IL-6 and IL-1ra. Regarding IL-15 and TNF-α, small to moderate effects were found. For IL-10, no significant effect was observed. Due to no data, meta-analyses for IL-7, TGF-ß1, and FKN could not be performed. No moderators (training status, type of exercise, risk of bias, age, sex, time of day, exercise volume, exercise intensity, exercise dose) of the results were detected for all tested myokines. Taken together, this systematic review and meta-analysis showed immediate positive effects of an acute resistance exercise session on IL-6, IL-1ra, TNF-α, and IL-15 levels.
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Interleucina-15 , Treinamento Resistido , Humanos , Interleucina-15/metabolismo , Interleucina-10/metabolismo , Interleucina-6/metabolismo , Miocinas , Proteína Antagonista do Receptor de Interleucina 1 , Fator de Necrose Tumoral alfa/metabolismo , Músculo Esquelético/metabolismo , Interleucina-7/metabolismo , Exercício Físico/fisiologiaRESUMO
Anatomically connected bones and muscles determine movement of the body. Forces exerted on muscles are then turned to bones to promote osteogenesis. The crosstalk between muscle and bone has been identified as mechanotransduction previously. In addition to the mechanical features, bones and muscles are also secretory organs which interact closely with one another through producing myokines and osteokines. Moreover, besides the mechanical features, other factors, such as nutrition metabolism, physiological rhythm, age, etc., also affect bone-muscle crosstalk. What's more, osteogenesis and myogenesis within motor system occur almost in parallel. Pathologically, defective muscles are always detected in bone associated diseases and induce the osteopenia, inflammation and abnormal bone metabolism, etc., through biomechanical or biochemical coupling. Hence, we summarize the study findings of bone-muscle crosstalk and propose potential strategies to improve the skeletal or muscular symptoms of certain diseases. Altogether, functional improvement of bones or muscles is beneficial to each other within motor system.
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Osso e Ossos , Músculo Esquelético , Humanos , Osso e Ossos/metabolismo , Osso e Ossos/patologia , Músculo Esquelético/metabolismo , Animais , Osteogênese/fisiologia , Mecanotransdução Celular , Desenvolvimento MuscularRESUMO
OBJECTIVES: To assess the ability of dual-energy X-ray absorptiometry (DXA) and hand-grip dynamometer to measure damage in inflammatory myopathies (IM). METHODS: . Forty adult IM patients with a disease duration ≥12 months, low or no disease activity for ≥6 months, were prospectively enrolled. Thirty healthy age and sex-matched volunteers were enrolled as controls. Whole-body DXA and hand-grip dynamometer were used to measure muscle mass, grip strength and diagnose sarcopenia (EWGSOP2 criteria). Relationships between the results of strength in 12 muscles, functional tests, patient-reported disability, IMACS damage score, and history of the disease were assessed. The serum levels of potential molecular actors of the damage were measured. RESULTS: DXA and grip strength measurements took ≤20 min. Both muscle mass and grip strength were decreased in IM patients vs volunteers (-10% and -30% respectively) with a dispersion that varied widely (IQR -24.3% to + 7.8% and -51.3% to -18.9% respectively). Muscle mass and grip strength were non-redundantly correlated (r up to 0.6, p= 0.0001) with strength in 14 muscles (manual muscle test and hand-held dynamometer), functions (of limbs, respiratory and deglutition muscles), patient-reported disability, damage (extension and severity in muscular and extra-muscular domains), and blood-levels of several myokines. Seven IM patients (17.5%) were sarcopenic. They had the worst damage, functions impairment, disability and history of severe myopathy. Decreased irisin and osteonectin levels were associated with sarcopenia (AUC 0.71 and 0.80, respectively). CONCLUSION: DXA and hand-grip dynamometer are useful tools to assess damage in IM. Irisin and osteonectin may play a role in IM damage pathogenesis.
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INTRODUCTION: Physical activity is associated with improved disease progression and cancer-specific survival in patients with prostate cancer (PCa). However, the mechanisms underlying these associations remain unclear, while the relative impact of exercise modes is unknown. This study aims to examine the differential impact of exercise mode on tumour-suppressive skeletal muscle-associated systemic molecules as well as their delivery mechanism. This study will compare the effects of the two main exercise modes, aerobic and resistance, on (1) circulatory myokine levels, (2) skeletal muscle-induced extracellular vesicle abundance and cargo contents, and (3) uptake of extracellular vesicles (EVs) in PCa cells in patients with localised or advanced PCa. METHODS: A single-group cross-over design will be used for patients at opposite ends of the disease spectrum. A total of 32 patients (localised PCa, n = 16; metastatic castrate-resistant PCa, n = 16) will be recruited while capitalising on two ongoing studies. Ethics amendment has been approved for two ongoing trials to share data, implement the acute exercise sessions, and collect additional blood samples from patients. The patients will undertake two exercise sessions (aerobic only and resistance only) in random order one week apart. Blood will be collected before, after, and 30 min post-exercise. Circulating/EV-contained myokine levels (irisin, IL-6, IL-15, FGF-21, and SPARC) and plasma skeletal muscle-induced EVs will be measured using ELISA and flow cytometry. PCa cell line growth with or without collected plasma will be examined using PCa cell lines (LNCaP, DU-145, and PC-3), while evaluating cellular uptake of EVs. Ethics amendments have been approved for two capitalising studies to share data, implement acute exercise sessions and collect additional samples from the patients. DISCUSSION: If findings show a differential impact of exercise mode on the establishment of an anti-cancer systemic environment, this will provide fundamental knowledge for developing targeted exercise prescriptions for patients with PCa across different disease stages. Findings will be reported in peer-reviewed publications and scientific conferences, in addition to working with national support groups to translate findings for the broader community. TRIAL REGISTRATION: The registration for the two capitalising studies are NCT02730338 and ACTRN12618000225213.
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Estudos Cross-Over , Exercício Físico , Vesículas Extracelulares , Miocinas , Neoplasias da Próstata , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Exercício Físico/fisiologia , Terapia por Exercício/métodos , Vesículas Extracelulares/metabolismo , Músculo Esquelético/metabolismo , Miocinas/sangue , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Neoplasias da Próstata/terapia , Estudos Clínicos como AssuntoRESUMO
BACKGROUND: The related functions of skeletal muscle and brain decrease significantly with age, and muscle-brain-related diseases are primarily associated with each other. Exercise can promote the secretion of myokines in skeletal muscle, showing a beneficial effect on the function of both, reflecting muscle-brain crosstalk. However, the key mechanism of action of exercise-regulated myokines in muscle-brain diseases remains unclear. SUMMARY: This review is intended to sort out and explore the key mechanism of the effect of exercise regulatory myokines on muscle-brain diseases through summarizing the relevant literature on the level of motor regulatory myokines in recent years and pay special attention to the impact of exercise type, intensity, and duration on myokine expression levels. KEY MESSAGES: The mechanism by which exercise regulates myokine levels in muscle-brain diseases is explained, and an effective exercise prescription for myokine expression that is more suitable for the elderly based on relevant literature is proposed. This work may hold certain value for subsequent exercise treatment of chronic diseases in the elderly and for further research on muscle-brain crosstalk.
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Encefalopatias , Miocinas , Humanos , Idoso , Citocinas/metabolismo , Músculo Esquelético/metabolismo , Encéfalo/metabolismo , Encefalopatias/metabolismo , EnvelhecimentoRESUMO
PURPOSE: To describe serum irisin and fibroblast growth factor-21 (FGF-21) concentrations in healthy female adolescents with different training activity patterns and their associations with bone mineral properties and metabolic markers. METHODS: A total of 62 adolescent girls aged 14-18 years were recruited: 22 rhythmic gymnasts, 20 swimmers, and 20 untrained controls. Bone mineral characteristics by dual-energy X-ray absorptiometry, daily energy intake by dietary recall, serum irisin, FGF-21, undercarboxylated osteocalcin, and C-terminal telopeptide of type I collagen were measured in all girls. RESULTS: Whole body and lumbar spine areal bone mineral density and lumbar spine bone mineral content were higher in the rhythmic gymnasts group compared with swimmers and untrained controls groups (P < .05). Serum irisin, FGF-21, undercarboxylated osteocalcin, and C-terminal telopeptide of type I collagen levels were not significantly different between the groups. In the rhythmic gymnasts group, serum FGF-21 concentration was positively correlated with lumbar spine areal bone mineral density independently of confounding factors (r = .51; P = .027). CONCLUSIONS: Serum irisin and FGF-21 levels were not different between adolescent eumenorrheic girls with different training activity patterns. FGF-21 was positively associated with lumbar spine areal bone mineral density, which predominantly consists of trabecular bone in adolescent rhythmic gymnasts.
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Arsenic is a well-known environmental toxicant and emerging evidence suggests that arsenic exposure has potential skeletal muscle toxicity; however, the underlying mechanism has not yet been clarified. The aim of this study was to investigate the correlation among adverse effects of subchronic and chronic environmental arsenic exposure on skeletal muscle as well as specific myokines secretion and angiotensin II (AngII)-melatonin (MT) axis in rats. Four-week-old rats were exposed to arsenite (iAs) in drinking water at environmental relevant concentration of 10 ppm for 3 or 9 months. Results indicated that the gastrocnemius muscle had atrophied and its mass was decreased in rats exposed to arsenite for 9 months, whereas, they had no significant changes in rats exposed to arsenite for 3 months. The levels of serum-specific myokine irisin and gastrocnemius muscle insulin-like growth factor-1 (IGF-1) were increased in 3-month exposure group and decreased in 9-month exposure group, while serum myostatin (MSTN) was increased significantly in 9-month exposure group. In addition, serum AngII level increased both in 3- and 9-month exposure groups, while serum MT level increased in 3-month exposure group and decreased in 9-month exposure group. Importantly, the ratio of AngII to MT level in serum increased gradually with the prolongation of arsenite exposure. It showed a certain correlation between AngII-MT axis and gastrocnemius muscle mass, gastrocnemius muscle level of IGF-1 or serum levels of irisin and MSTN. In conclusion, the disruption of AngII-MT axis balance may be a significant factor for skeletal muscle atrophy induced by chronic environmental arsenic exposure.
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Arsênio , Arsenitos , Melatonina , Ratos , Animais , Angiotensina II , Fator de Crescimento Insulin-Like I , Melatonina/farmacologia , Arsenitos/toxicidade , Fibronectinas , Músculo Esquelético , AtrofiaRESUMO
Interaction with the environment appears necessary for the maturation of sensorimotor and cognitive functions in early life. In rats, a model of sensorimotor restriction (SMR) from postnatal day 1 (P1) to P28 has shown that low and atypical sensorimotor activities induced the perturbation of motor behavior due to muscle weakness and the functional disorganization of the primary somatosensory and motor cortices. In the present study, our objective was to understand how SMR affects the muscle-brain dialogue. We focused on irisin, a myokine secreted by skeletal muscles in response to exercise. FNDC5/irisin expression was determined in hindlimb muscles and brain structures by Western blotting, and irisin expression in blood and cerebrospinal fluid was determined using an ELISA assay at P8, P15, P21 and P28. Since irisin is known to regulate its expression, Brain-Derived Neurotrophic Factor (BDNF) levels were also measured in the same brain structures. We demonstrated that SMR increases FNDC5/irisin levels specifically in the soleus muscle (from P21) and also affects this protein expression in several brain structures (as early as P15). The BDNF level was increased in the hippocampus at P8. To conclude, SMR affects FNDC5/irisin levels in a postural muscle and in several brain regions and has limited effects on BDNF expression in the brain.
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Fator Neurotrófico Derivado do Encéfalo , Fibronectinas , Animais , Ratos , Encéfalo , Músculo Esquelético , CogniçãoRESUMO
Type 2 diabetes (T2D) is characterized by muscle metabolic dysfunction that exercise can minimize, but some patients do not respond to an exercise intervention. Myokine secretion is intrinsically altered in patients with T2D, but the role of myokines in exercise resistance in this patient population has never been studied. We sought to determine if changes in myokine secretion were linked to the response to an exercise intervention in patients with T2D. The participants followed a 10-week aerobic exercise training intervention, and patients with T2D were grouped based on muscle mitochondrial function improvement (responders versus non-responders). We measured myokines in serum and cell-culture medium of myotubes derived from participants pre- and post-intervention and in response to an in vitro model of muscle contraction. We also quantified the expression of genes related to inflammation in the myotubes pre- and post-intervention. No significant differences were detected depending on T2D status or response to exercise in the biological markers measured, with the exception of modest differences in expression patterns for certain myokines (IL-1ß, IL-8, IL-10, and IL-15). Further investigation into the molecular mechanisms involving myokines may explain exercise resistance with T2D; however, the role in metabolic adaptations to exercise in T2D requires further investigation.
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Diabetes Mellitus Tipo 2 , Terapia por Exercício , Fibras Musculares Esqueléticas , Treinamento Resistido , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Citocinas/metabolismo , Citocinas/sangue , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/terapia , Terapia por Exercício/métodos , Interleucina-10/metabolismo , Interleucina-10/sangue , Interleucina-15/metabolismo , Interleucina-15/sangue , Interleucina-1beta/metabolismo , Interleucina-1beta/sangue , Interleucina-8/metabolismo , Interleucina-8/sangue , Contração Muscular , Fibras Musculares Esqueléticas/metabolismo , Músculo Esquelético/metabolismo , MiocinasRESUMO
We considered in this study the possibility of developing an indirect procedure for detecting myostatin inhibition/suppression, a practice that is prohibited as doping in sport. We have specifically considered the potential diagnostic utility of human serum myokines as indirect markers of myostatin inhibition. Myostatin, its main antagonist follistatin, and other myokines (follistatin-like 1, musclin, oncostatin, osteonectin, irisin, brain derived neurotrophic factor, and insulin-like growth factor-1) were selected as a panel of potential biomarkers whose levels may be altered following myostatine suppression. The serum levels of myostatin and of the nine myokines were measured in elite athletes of different age, sex, and sport discipline, and their cross correlation assessed by multivariate analysis. All myokines resulted to be measurable in human serum, except for musclin and irisine, whose levels were below the limits of quantitation in a reduced number of samples. Serum concentrations varied of different orders in magnitude (musclin and osteonectin < 1 ng/mL; follistatin, myostatine and irisine 1-5 ng/mL; brainderived neurotrophic factor, follistatin-like 1 and iinsulin-like growth factor-1 > 10 ng/mL), while no significant differences were found between female and male subjects, with the exceptions of follistatin-like 1 and musclin, showing a higher concentrations in females (p < 0.05). Levels of insulin-like growth factor 1 and brain derived neurotrophic factor were significantly higher in power athletes than in endurance ones. Multivariate statistics showed that musclin, follistatin-like 1 and oncostatin are more clustered and correlated to myostatin than other myokines, suggesting they could be considered as potential biomarkers of doping by myostatin inhibitors.
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High intensity interval training (HIIT) has been shown to consistently elicit rapid and significant adaptations in a number of physiological systems, across many different healthy and clinical populations. In addition, there is increasing interest in how some acute, yet transient responses to high intensity exercise potentially reduce the risks of particular diseases. Recent work has shown that discrete, brief bouts of high intensity exercise (termed 'exercise snacks') can improve glucose control and vascular health and thus counter the negative cardiometabolic consequences of prolonged, uninterrupted periods of inactivity. In this brief review, we advance the case, using evidence available from pre-clinical studies in the exercise oncology literature, that brief, frequently completed bouts of high intensity exercise embedded within an individual's overall daily and weekly physical activity schedule, may transiently impact the tumour microenvironment and improve the health outcomes for those who have been diagnosed and treated for cancer.
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Doenças Cardiovasculares , Neoplasias , Humanos , Lanches , Exercício Físico/fisiologia , Doenças Cardiovasculares/prevenção & controle , Neoplasias/terapia , Microambiente TumoralRESUMO
Brown and beige adipose tissue share similar functionality, being both tissues specialized in producing heat through nonshivering thermogenesis and also playing endocrine roles through the release of their secretion factors called batokines. This review elucidates the influence of physical exercise, and myokines released in response, on the regulation of thermogenic and secretory functions of these adipose tissues and discusses the similarity of batokines actions with physical exercise in the remodeling of adipose tissue. This adipose tissue remodeling promoted by autocrine and paracrine batokines or physical exercise seems to optimize its functionality associated with better health outcomes.
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Tecido Adiposo Bege , Tecido Adiposo Marrom , Humanos , Termogênese/fisiologia , Obesidade , Exercício FísicoRESUMO
PURPOSE: Beyond classical procedures, bioinformatic-assisted approaches and computational biology offer unprecedented opportunities for scholars. However, these amazing possibilities still need epistemological criticism, as well as standardized procedures. Especially those topics with a huge body of data may benefit from data science (DS)-assisted methods. Therefore, the current study dealt with the combined expert-assisted and DS-assisted approaches to address the broad field of muscle secretome. We aimed to apply DS tools to fix the literature research, suggest investigation targets with a data-driven approach, predict possible scenarios, and define a workflow. METHODS: Recognized scholars with expertise on myokines were invited to provide a list of the most important myokines. GeneRecommender, GeneMANIA, HumanNet, and STRING were selected as DS tools. Networks were built on STRING and GeneMANIA. The outcomes of DS tools included the top 5 recommendations. Each expert-led discussion has been then integrated with an DS-led approach to provide further perspectives. RESULTS: Among the results, 11 molecules had already been described as bona-fide myokines in literature, and 11 molecules were putative myokines. Most of the myokines and the putative myokines recommended by the DS tools were described as present in the cargo of extracellular vesicles. CONCLUSIONS: Including both supervised and unsupervised learning methods, as well as encompassing algorithms focused on both protein interaction and gene represent a comprehensive approach to tackle complex biomedical topics. DS-assisted methods for reviewing existent evidence, recommending targets of interest, and predicting original scenarios are worth exploring as in silico recommendations to be integrated with experts' ideas for optimizing molecular studies.
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Músculo Esquelético , Secretoma , Humanos , Músculo Esquelético/metabolismo , Exercício Físico/fisiologia , Biologia Computacional/métodosRESUMO
PURPOSE OF REVIEW: Strong evidence is evolving that physical exercise prevents hypertension and reduces blood pressure in patients with pre- and manifest HTN. Yet, identifying and confirming the effectiveness of exercise are challenging. Herein, we discuss conventional and novel biomarkers such as extracellular vesicles (EVs) which may track responses to HTN before and after exercise. RECENT FINDINGS: Evolving data shows that improved aerobic fitness and vascular function as well as lowered oxidative stress, inflammation, and gluco-lipid toxicity are leading biomarkers considered to promote HTN, but they explain only about a half of the pathophysiology. Novel biomarkers such as EVs or microRNA are providing additional input to understand the complex mechanisms involved in exercise therapy for HTN patients. Conventional and novel biomarkers are needed to fully understand the integrative "cross-talk" between tissues to regulate vasculature physiology for blood pressure control. These biomarker studies will lead to more specific disease markers and the development of even more personalized therapy in this field. However, more systematic approaches and randomized controlled trials in larger cohorts are needed to assess exercise effectiveness across the day and with different exercise types.
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Hipertensão , MicroRNAs , Humanos , Hipertensão/terapia , Exercício Físico/fisiologia , Pressão Sanguínea , BiomarcadoresRESUMO
Skeletal muscle has a robust endocrine function as a powerful organ and can secrete and release cytokines or polypeptides known as myokines. These myokines have significant regulatory effects on signal transduction in skeletal muscle and the metabolism of peripheral tissues and organs and exert biological effects via autocrine, paracrine, or endocrine forms. Obesity and aging cause myokine secretion dysregulation, and hastening sarcopenic obesity (SO) development. Exercise is currently an excellent intervention and prevention method for SO. Meanwhile, exercise impacts many organs and tissues. These organs and tissues will produce various myokines in response to movement and metabolism throughout the body to govern muscle differentiation, growth, and remodeling. According to accumulating data, exercise can increase the release of myokines from diverse tissues into the blood and postpone the SO onset and progression by influencing protein metabolism, inflammation, mitochondrial quality control, and other mechanisms.
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Citocinas , Sarcopenia , Humanos , Citocinas/metabolismo , Sarcopenia/terapia , Sarcopenia/metabolismo , Exercício Físico/fisiologia , Músculo Esquelético/metabolismo , Obesidade/terapia , Obesidade/metabolismoRESUMO
The skeletal muscle is an endocrine organ that produces proteins and peptides, collectively termed as myokines. The temperature of skeletal muscles varies during exercise and/or with changes in ambient temperature. However, whether myokine secretion is regulated by heat stimulation is unclear. Thus, we aimed to explore the effects of environmental heat stimulation on myokine secretion. We initially investigated the secretome of C2C12 myotubes and identified several novel heat-responsive myokines. The concentration of C-C motif chemokine ligand 5 (CCL5) dramatically decreased by 0.3-fold in response to heat stress. After 3 h heat stimulation of C2C12 cells, the expression of heat shock protein 70 was induced, and the gene expression and secretion of CCL5 was significantly attenuated in C2C12 cells. We then examined the effects of acute heat stress on serum CCL5 levels in mice and Ccl5 gene expression in skeletal muscles. Mice were maintained at 23°C, exposed to 45°C for 30 min, and then returned to the 23°C chamber for recovery. The expression of Ccl5 in the skeletal muscle significantly decreased after 3 h of recovery. Serum CCL5 levels increased by approximately 1.9-fold after 30 min of heat exposure and then significantly decreased by approximately 0.7-fold after 23 h of recovery. This study suggests that heat stimulation decreases CCL5 secretion from the skeletal muscle in vitro and in vivo. Given its fundamental role in inflammation by recruiting several immune cells, CCL5 has a potential role in controlling inflammatory responses in the body after heat stimulation.
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Fibras Musculares Esqueléticas , Músculo Esquelético , Animais , Camundongos , Ligantes , Fibras Musculares Esqueléticas/metabolismo , Músculo Esquelético/metabolismo , Expressão Gênica , Quimiocinas/metabolismoRESUMO
Exercise-released extracellular vesicles (EVs) are emerging as a novel class of exerkines that promotes systemic beneficial effects. However, slight differences in the applied exercise protocols in terms of mode, intensity and duration, as well as the need for standardized protocols for EV isolation, make the comparison of the studies in the literature extremely difficult. This work aims to investigate the EV amount and EV-associated miRNAs released in circulation in response to different physical exercise regimens. Healthy individuals were subjected to different exercise protocols: acute aerobic exercise (AAE) and training (AT), acute maximal aerobic exercise (AMAE) and altitude aerobic training (AAT). We found a tendency for total EVs to increase in the sedentary condition compared to trained participants following AAE. Moreover, the cytofluorimetric analysis showed an increase in CD81+/SGCA+/CD45- EVs in response to AAE. Although a single bout of moderate/maximal exercise did not impact the total EV number, EV-miRNA levels were affected as a result. In detail, EV-associated miR-206, miR-133b and miR-146a were upregulated following AAE, and this trend appeared intensity-dependent. Finally, THP-1 macrophage treatment with exercise-derived EVs induced an increase of the mRNAs encoding for IL-1ß, IL-6 and CD163 using baseline and immediately post-exercise EVs. Still, 1 h post-exercise EVs failed to stimulate a pro-inflammatory program. In conclusion, the reported data provide a better understanding of the release of circulating EVs and their role as mediators of the inflammatory processes associated with exercise.
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Vesículas Extracelulares , MicroRNAs , Humanos , MicroRNAs/genética , Macrófagos , Exercício FísicoRESUMO
The mineralocorticoid receptor (MR) is able to regulate the transcription of a number of genes in the myotube, although its roles in skeletal muscle (SM) metabolism still await demonstration. SM represents a major site for glucose uptake, and its metabolic derangements play a pivotal role in the development of insulin resistance (IR). The aim of this study was to investigate the contribution of SM MR in mediating derangements of glucose metabolism in a mouse model of diet-induced obesity. We observed that mice fed a high-fat diet (HFD mice) showed impaired glucose tolerance compared to mice fed a normal diet (ND mice). Mice fed a 60% HFD treated with the MR antagonist Spironolactone (HFD + Spiro) for 12 weeks revealed an improvement in glucose tolerance, as measured with an intraperitoneal glucose tolerance test, compared with HFD mice. To investigate if blockade of SM MR could contribute to the favorable metabolic effects observed with pharmacological MR antagonism, we analyzed MR expression in the gastrocnemius, showing that SM MR protein abundance is downregulated by HFD compared to ND mice and that pharmacological treatment with Spiro was able to partially revert this effect in HFD + Spiro mice. Differently from what we have observed in adipose tissue, where HDF increased adipocyte MR expression, SM MR protein was down-regulated in our experimental model, suggesting a completely different role of SM MR in the regulation of glucose metabolism. To confirm this hypothesis, we investigated the effects of MR blockade on insulin signaling in a cellular model of IRin C2C12 myocytes, which were treated with or without Spiro. We confirmed MR protein downregulation in insulin-resistant myotubes. We also analyzed Akt phosphorylation upon insulin stimulation, and we did not observe any difference between palmitate- and palmitate + Spiro-treated cells. These results were confirmed by in vitro glucose uptake analysis. Taken together, our data indicate that reduced activity of SM MR does not improve insulin signaling in mouse skeletal myocytes and does not contribute to the favorable metabolic effects on glucose tolerance and IR induced by systemic pharmacological MR blockade.
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Resistência à Insulina , Receptores de Mineralocorticoides , Animais , Camundongos , Receptores de Mineralocorticoides/metabolismo , Músculo Esquelético/metabolismo , Resistência à Insulina/fisiologia , Insulina/metabolismo , Dieta Hiperlipídica/efeitos adversos , Glucose/metabolismo , Palmitatos/metabolismo , Camundongos Endogâmicos C57BLRESUMO
The purpose of the study was to assess the impact of single whole-body cryostimulation (WBC) preceding submaximal exercise on oxidative stress and inflammatory biomarkers in professional, male athletes. The subjects (n = 32, age 25.2 ± 37) were exposed to low temperatures (-130 °C) in a cryochamber and then participated in 40 min of exercise (85% HRmax). Two weeks afterwards, the control exercise (without WBC) was performed. Blood samples were taken before the start of the study, immediately after the WBC procedure, after exercise preceded by WBC (WBC exercise) and after exercise without WBC. It has been shown that catalase activity after WBC exercise is lower in comparison with activity after control exercise. The interleukin 1ß (IL-1-1ß) level was higher after control exercise than after WBC exercise, after the WBC procedure and before the start of the study (p < 0.01). The WBC procedure interleukin 6 (IL-6) level was compared with the baseline level (p < 0.01). The level of Il-6 was higher both after WBC exercise and after control exercise compared with the level recorded after the WBC procedure (p < 0.05). Several significant correlations between the studied parameters were shown. In conclusion, the changes in the cytokine concentration in the athletes' blood confirm that body exposition to extremely low temperatures before exercise could regulate the inflammatory reaction course and secretion of cytokines during exercise. A single session of WBC in the case of well-trained, male athletes does not significantly affect the level of oxidative stress indicators.