Gut microbial metabolite increases skeletal muscle regeneration through epigenetic mechanisms

Introduction: Reduction in skeletal muscle regeneration capacity, such as in inflammatory muscle diseases and aging, leads to progressive muscle strength decrement, which impairs mobility and increases risk of falls and mortality, with a negative impact of quality of life. This reduction in skeletal muscle regeneration has been associated with an impaired function of the skeletal muscle stem cells, namely, the satellite cells. These cells are localized beneath basal lamina in a quiescence state and can be activated and differentiated into new myofibers after muscle damage. Indeed, satellite cells need to exit the cell cycle for differentiation. Therefore, the search for biological tools that can improve activation/differentiation of satellite cells is of great interest to regenerative medicine. In this regard, butyrate, a gut microbial metabolite, which can induce cell cycle arrest through histone deacetylase inhibition, has emerged as a therapeutic tool in some diseases, such as cancer. Then, we hypothesize that butyrate could improve skeletal muscle regeneration by accelerating satellite cellsdifferentiation into myofibers through epigenetics mechanisms related to cell cycle exit. Objectives: To assess whether butyrate could improve skeletal muscle regeneration after barium chloride damage and its epigenetics mechanisms. Methods: Twenty C57Bl/6 male mice (CEUA: 133/2014), with 8 weeks of age, were grouped as follows: (1) control group with no injury + saline (C-Sal); (2) control group with no injury + butyrate (CBut); (3) injury with saline (I-Sal);and (4) injury + butyrate (I-But). The muscle injury was performed with the injection of 50 μL of barium chloride (1.2%) in both tibialis anterior and the muscles were harvested six and twelve days after injury for histological and molecular analyses. Butyrate were injected intraperitoneally (400 mg/kg) for 6 days. For in vitro assays, primary satellite cells were isolated and cultured as myoblasts. Myoblasts were treated with 300 μM of butyrate during proliferation and differentiation conditions in order to assess cell cycle molecules, differentiation index, and epigenetics mechanisms. The significance was assumed when P < 0.05. Results: Skeletal muscle regeneration, assessed by cross-sectional area of tibialis anterior muscle, was higher in I-But than I-Sal group (P < 0.05). Histogram analysis also showed higher frequency of smaller fibers in I-Sal than I-But group (P < 0.05). In vitro analyses showed a reduction in the myoblasts proliferation when treated with butyrate (P < 0.05). Also, butyrate treatment downregulated genes related to cell cycle activation (cdk1, cdk2, cdk4), and up-regulated genes related to cell cycle repression (p57) (P < 0.05). The myotubes differentiation, assessed by fusion index, were higher in myoblasts treated with butyrate (P < 0.05), which was followed by an upregulation of the myogenic marker of differentiation, myogenin (P < 0.05). Moreover, butyrate was able to decrease histone deacetylase (P < 0.05) and increase histone acetyltransferase enzymatic activities (P < 0.05). Conclusion and discussion: Butyrate increased skeletal muscle regeneration in mice by accelerating the myotubes differentiation through induction of cell cycle arrest in myoblasts. Preliminary data suggested that this improvement was epigenetically mediated

Atividade física habitual e variabilidade da frequência cardíaca de repouso em nipo-brasileiros praticantes e não praticantes de PARK GOLF

The aims of this study were to compare the habitual physical activity (HPA) level by means of steps.day-1 and the resting heart rate variability (HRV) parameters of nipo-brazilians practitioners (GPG) and non-practitioners (GNP) of Park Golf and verify the correlations between HPA and HRV. Thirty three subjects of both genders (68.2±6.3 years) participated of this study, being 20 subjects in GPG (68.3±6.3 years) and 13 in GNP (68.2±6.4 years). The subjects wore the pedometer for one week to measure the HPA. The HRV was analyzed beat-to-beat at rest in the supine position using a heart rate monitor and the respiratory frequency was controlled in 12 respiratory cycles per minute. The HPA level was higher in GPG when compared to GNP. There were no differences in the HRV between groups. Regarding gender, women presented higher mean steps.day-1 and parasympathetic indices of HRV. Men presented higher sympathetic indices. The HPA level was significantly correlated with body mass index (BMI) and with the mean R-R intervals. The greater HPA level reported in GPG was not sufficient to induce a more favorable resting HRV than in GNP.Os objetivos deste estudo foram comparar o nível de atividade física habitual (AFH) por meio do número de passos.dia-1 e os parâmetros da variabilidade da frequência cardíaca (VFC) de repouso em nipo-brasileiros praticantes (GPG) e não praticantes (GNP) de Park Golf e verificar as correlações entre o nível de AFH e a VFC. Trinta e três indivíduos de ambos os gêneros (68,2±6,3 anos) fizeram parte do estudo, sendo 20 sujeitos no GPG (68,3±6,3 anos) e 13 no GNP (68,2±6,4 anos). Os sujeitos utilizaram o pedômetro por uma semana para mensurar a AFH. A VFC foi analisada batimento-a-batimento no repouso em decúbito dorsal por meio de um cardiofrequencímetro. Durante a avaliação da VFC, houve controle da freqüência respiratória em 12 respirações por minuto. A AFH foi maior no GPG quando comparado ao GNP. Não foram observadas diferenças nos indicadores da VFC entre os grupos. Em relação aos gêneros, as mulheres apresentaram maiores médias de passos.dia-1 e valores de índices parassimpáticos pela VFC. Os homens obtiveram maiores índices simpáticos. O nível de AFH apresentou correlação significante com o índice de massa corporal (IMC) e com a média dos intervalos R-R. O maior nível de AFH encontrado no GPG não foi suficiente para promover VFC de repouso mais favorável em relação ao GNP

Effects of acute and chronic aerobic exercise in serum levels of cytokines and in gene expression of circulating leukocytes in patients with systemic lupus erythematosus

Introdução: O lúpus eritematoso sistêmico (LES) é uma doença autoimune caracterizada por uma alteração no sistema imunológico e uma inflamação crônica. O exercício físico agudo e crônico têm sido apontados como uma estratégia capaz de atenuar os acometimentos da doença e os fatores de risco cardiovasculares em pacientes com LES. Entretanto, ainda não se sabe se o exercício físico poderia piorar o quadro inflamatório e imunológico de pacientes com LES em remissão (LESREM) e atividade da doença (LESATIV). Objetivos: Avaliar o efeito agudo e crônico do exercício aeróbio na resposta das citocinas (IFN-y, IL-10, IL-6 e TNF-alfa) e receptores solúveis de TNF (sTNFR1 e sTNFR2) séricos e na expressão gênica em leucócitos circulantes de pacientes com LESREM e LESATIV. Métodos: A resposta das citocinas e dos sTNFRs às sessões agudas de exercício moderado (~50% do VO2pico) e intenso (~70% do VO2pico) foram avaliadas em 11 pacientes com LESATIV, 12 pacientes com LESREM e 10 controles saudáveis (GC), os quais foram pareados por sexo, idade e índice de massa corporal. A resposta da expressão gênica em leucócitos circulantes à sessão aguda intensa de exercício foi avaliada em quatro voluntárias por grupo (LESATIV, LESREM e GC). O treinamento aeróbio (12 semanas, 2x/semana, 30 a 50 minutos, FC entre os limiares ventilatórios) foi realizado por oito pacientes com LESREM. As citocinas e os sTNFRs foram avaliados por multiplex e a expressão gênica pelo método de PCRarray, com subsequente análise bioinformática. Resultados: Em resposta a sessão aguda moderada de exercício não houve alteração na resposta das citocinas e receptores solúveis de TNF (P > 0,05), com exceção da redução da IL-6 e do sTNFR1 na recuperação nos grupos LESATIV e GC (P 0,05), enquanto o IFN-y reduziu ao final do exercício (P = 0,05) e a IL-6 apresentou um aumento transitório ao final do exercício (P = 0,028). No grupo LESATIV, houve um aumento transitório da IL-10, IL-6 e TNF-alfa (P 0,05). Conclusão: As sessões agudas de exercício moderado e intenso não exacerbam o quadro inflamatório em pacientes com LESREM e LESATIV. Adicionalmente, uma sessão intensa de exercício parece modular a expressão gênica em leucócitos circulantes de pacientes com LESREM e LESATIV, porém, em menor quantidade comparados ao GC. Por fim, o treinamento aeróbio parece reduzir o milieu inflamatório em pacientes com LESREMBackground: Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by an altered immune system and a chronic inflammation. Acute and chronic physical exercise has been emerged as a strategy to attenuate the disease outcomes and the cardiovascular risk factors in SLE patients. However, it is not known yet if physical exercise could dysregulate the inflammatory process and immune system in active (SLEACTIVE) and inactive SLE patients (SLEINACTIVE). Aims: to assess the effects of acute and chronic aerobic exercise training on the serum cytokines (IFN-y, IL-10, IL-6 e TNF-?) and soluble TNF receptors (sTNFR1 and sTNFR2) levels and in the gene expression of circulating leukocytes in SLEACTIVE and SLEINACTIVE patients. Methods: Cytokines and sTNFRs responses to acute moderate (~50% of VO2peak) and intense (~70% of VO2peak) aerobic exercise were assessed in 11 SLEACTIVE patients, 12 SLEINACTIVE patients and 10 healthy controls (HC), who were matched for age, sex and body mass index. Leucocytes gene expression responses to acute intense exercise were assessed in four subjects of each group (SLEACTIVE, SLEINACTIVE, and HC). Aerobic exercise training (12 weeks, twice a week, 30 to 50 minutes, HR between ventilatory thresholds) was performed by eight SLEINACTIVE patients. Cytokines and sTNFRs were assessed by multiplex technique and the gene expression by a PCRarray method, followed by bioinformatics analysis. Results: In response to an acute moderate exercise there were no significant differences in cytokines and sTNFRs (P > 0.05), except for the reduction in IL-6 and sTNFR1 during recovery in SLEACTIVE and HC (P 0.05), while IFN-y reduced at the end of exercise (P = 0.05) and IL-6 increased transitorily at the end of exercise (P = 0.028). In the SLEACTIVE group, there was a transitory increase in IL-10, IL-6 and TNF-alfa (P 0.05). Conclusion: Acute moderate and intense aerobic exercise did not exacerbate the inflammatory process in SLEINACTIVE and SLEACTIVE patients. Additionally, acute intense aerobic exercise seems to modulate the gene expression in leukocytes of SLEINACTIVE and SLEACTIVE patients, however, in fewer genes than in HC group. Finally, the aerobic exercise training seems to reduce milieu inflammatory in SLEINACTIVE patient

<b> Correlation between critical force and critical velocity and their respective stroke rates </b>

<p> The critical power model has been utilized to estimate the anaerobic and aerobic capacities in swimming. There are studies which evidence the applicability of swimming velocity, force during tethered swimming and stroke rate data to the critical power model. However, the relationship among these estimates derived from freestyle and tethered swimming needs to be established. Therefore, the aim of this study was to evaluate the relationship between critical force (FCRIT) obtained from tethered swimming and critical velocity (VCRIT) during freestyle swimming (VCRIT), and their respective critical stroke rates (FBrCRIT). Eleven swimmers of both sexes (16.6 ± 1.3 years, 60 ± 10 kg, 172 ± 8 cm) underwent maximal tests to exhaustion in the tethered system and to as fast as possible trials during 200 and 400 m freestyle swimming. There were estimates of: 1) FCRIT and CIAnaer fi tting the three known equations derived from the critical power model (hyperbolic forcetime F-t, linear force-1/time F-1/t, linear impulse-time I-t); 2) VCRIT and CNAnaer during the freestyle tests using the linear distance-time relationship (d-t) and; 3) FBrCRIT and CBrAnaer during both kinds of tests (tethered and freestyle). The tethered performance data presented a good fi tting to the critical power model: FCRIT (R2 of 0.98, 0.97 and 0.99) and FBrCRIT-TETHERED (R2 of 0.96, 0.90 and 0.99). There was a high correlation between VCRIT and FCRIT (r= 0.89-0.91). Nevertheless, there was no signifi cant correlation among the estimates of FBrCRIT-TETHERED and FBrCRIT-FREESTYLE, neither among the anaerobic variables. These results indicate that FCRIT can be considered a reliable aerobic capacity index. However, the FBrCRIT-TETHERED did not approach this capacity, despite the good fi tting to the critical power model. <p> <b> RESUMO </b> O modelo da potência crítica tem sido utilizado para estimar a capacidade anaeróbia e aeróbia na natação. Há estudos demonstrando que a velocidade de nado livre, força no nado atado e freqüência de braçadas aderem ao modelo da potência crítica. Entretanto, a relação entre essas estimativas no nado livre e atado necessita ser elucidada. Assim, o objetivo do estudo foi avaliar a relação entre a força crítica (FCRIT) no nado atado e a velocidade crítica (VCRIT) em nado livre e as respectivas freqüências críticas de braçada (FBrCRIT). Onze nadadores de ambos os sexos (16,6 ± 1,3 anos, 60 ± 10 kg, 172 ± 8 cm) foram submetidos à natação atada até a exaustão e esforços máximos livres em 200 e 400 m. Foram estimados: 1) FCRIT e CIAnaer através três equações do modelo de potência crítica (hiperbólica força-tempo F-t, linear força-1/tempo F-1/t, linear impulso-tempo I-t); 2) VCRIT e CNAnaer na natação livre através da relação distância-tempo (d – t) e; 3) FBrCRIT e CBrAnaer nos dois testes (atado e livre). No nado atado houve elevado grau de ajuste dos dados ao modelo da potência crítica: FCRIT (R2 de 0,98, 0,97 e 0,99) e FBrCRIT-ATADO (R2 de 0,96, 0,90 e 0,99). Houve correlação signifi cativa entre a VCRIT e FCRIT (r = 0,89-0,91). Entretanto, não houve correlação signifi cativa entre as FBrCRIT-ATADO e a FBrCRIT-LIVRE, nem entre as variáveis anaeróbias. Esses resultados indicam que a FCRIT pode ser apontada como um indicador de capacidade aeróbia. Porém, a FBrCRIT-ATADO, apesar de se ajustar ao modelo de potência crítica, não se mostrou um bom indicador desta capacidade

Oxygen uptake kinetics during supra-maximal exercise: Mathematical modelling

http://dx.doi.org/10.5007/1980-0037.2008v10n1p43 Precise estimation of oxygen uptake kinetics parameters is essential to understand its control and/or limit uptake mechanisms. The purpose of the present study was to characterize the oxygen uptake kinetics responses during supramaximal cycle ergometer exercise using two modeling techniques. Eleven male subjects (age = 25.4 ± 4.9 years, height = 177.0 ± 4.0 cm, mass = 77.1 ± 11.3 kg, VO2max = 40.3 ± 6.3 mL.kg-1.min-1) performed a series of square- have exercise transitions to exhaustion at intensities equivalent to 100, 113, 133 and 153% of VO2max. The time constant of the primary component was estimated with an exponential and semi-logarithmic model, comparisons were made using repeated measures ANOVA and the Tukey post hoc tests, with statistical signifi cance accepted when p<0.05. In order to calculate the time constant by the semi-logarithmic model it is necessary to estimate oxygen demand, which was performed by means of a regression procedure. The exponential model resulted in lower values for the time constant (35.1 ± 8.0s; 32.5 ± 7.4s; 29.6 ± 11.3s; 25.3 ± 7.5s) compared to the semi-logarithmic model (107.9 ± 27.1s; 104.5 ± 24.3s; 114.1 ± 30.4s; 125.3 ± 24.9s) at all intensities. The observation of this confl icting oxygen uptake kinetics behavior depending upon which mathematical model is applied suggests that physiological inferences on the basis of parameters obtained during supra-maximal exercise should be made with caution

Índices técnicos correspondentes à velocidade crítica e à máxima velocidade de 30 minutos em nadadores com diferentes níveis de performance aeróbia Technical indexes corresponding to the critical speed and the maximal speed of 30 minutes in swimmers with different aerobic performance levels

O principal objetivo deste estudo foi verificar o efeito do nível de performance aeróbia na relação entre os índices técnicos correspondentes à velocidade crítica (VC) e à velocidade máxima de 30 minutos (V30) em nadadores. Participaram deste estudo, 23 nadadores do gênero masculino com características antropométricas similares, divididos segundo o nível de performance aeróbia em grupo G1 (maior performance) (n = 13) e G2 (menor performance) (n = 10). Os indivíduos tinham pelo menos quatro anos de experiência no esporte e treinavam um volume semanal de 30.000 a 45.000m. A VC foi determinada através do coeficiente angular da regressão linear entre as distâncias (200 e 400m) e seus respectivos tempos. A V30 foi determinada através da máxima distância realizada em um teste de 30 minutos. Todas as variáveis foram determinadas no nado crawl. A VC foi significantemente maior do que a V30 no grupo G1 (1,30 ± 0,04 vs. 1,23 ± 0,06m.s-1) e no G2 (1,17 ± 0,08 vs. 1,07 ± 0,06m.s-1). As duas variáveis foram maiores no grupo G1. As taxas de braçada correspondentes à VC (TBVC) e à V30 (TBV30) obtidas nos grupos G1 (33,07 ± 4,34 vs. 31,38 ± 4,15 ciclos.min-1) e G2 (35,57 ± 6,52 vs. 33,54 ± 5,89 ciclos.min-1) foram similares entre si. A TBVC foi significantemente menor no grupo 1 do que no grupo 2, enquanto que a TBV30 não foi diferente entre os grupos. Os comprimentos de braçada correspondentes à VC (CBVC) e à V30 (CBV30) foram significantemente maiores no grupo G1 (2,41 ± 0,33 vs. 2,38 ± 0,30m.ciclo-1) do que no G2 (2,04 ± 0,43 vs. 1,97 ± 0,40m.ciclo-1), e similares entre si nos dois grupos. As correlações (r) entre a VC e a V30 e as variáveis técnicas correspondentes às duas velocidades foram significantes em todas as comparações (0,68 a 0,91). Portanto, a relação entre a velocidade e as variáveis técnicas correspondentes à VC e à V30 não é modificada pelo nível de performance aeróbia.<br>The main objective of this study was to verify the effect of aerobic performance level on the relationship between the technical indexes corresponding to critical speed (CS) and maximal speed of 30 minutes (S30) in swimmers. Participated of this study 23 male swimmers with similar anthropometric characteristics, divided by aerobic performance level in groups G1 (n = 13) and G2 (n = 10). They had at least four years of experience in the modality and a weekly training volume between 30,000 to 45,000 m. The CS was determined through the angular coefficient of the linear regression line between the distances (200 and 400 m) and respective times. The S30 was determined through the maximal distance covered in a 30 minutes test. All variables were determined in front crawl. CS was higher than S30 in G1 (1.30 ± 0.04 vs. 1.23 ± 0.06 m.s-1) and G2 (1.17 ± 0.08 vs. 1.07 ± 0.06 m.s -1). These variables were higher in group G1. The stroke rate corresponding to CS (SRCS) and S30 (SRS30) obtained in group G1 (33.07 ± 4.34 vs. 31.38 ± 4.15 cycles.min-1) and G2 (35.57 ± 6.52 vs. 33.54 ± 5.89 cycles.min-1) were similar. The SRCS was significantly lower in group G1 than G2, while SRS30 was not different between groups. The stroke length corresponding to CS (SLCS) and S30 (SLS30) was significantly higher in group G1 (2.41 ± 0.33 vs. 2.38 ± 0.30 m.cycle-1) than in G2 (2.04 ± 0.43 vs. 1.97 ± 0.40 m.cycle-1), and had similar values in both groups. The correlation (r) between CS and S30 and technical variables corresponding to CS and S30 were significant in all comparisons (0.68 to 0.91). Thus, the relationship between the speed and technical variables corresponding to CS and S30 was not modified by the aerobic performance level