RESUMEN
Estradiol (E2) deficiency arising from menopause is closely related to changes in body composition and declines of muscle mass and strength in elderly women. Whole-body vibration training (WBV) is an emerging approach expected to improve muscle mass and strength of older person, but the underlying mechanisms remain unclear. The balance between protein synthesis and degradation is a determining factor for muscle mass and strength, which is regulated by Akt-mTOR and FoxO1 signal pathway, respectively. In the present study, we firstly determined whether the effects of WBV on muscle mass and strength in ovariectomized female mice was affected by estrogen level, then investigated whether this was associated with Akt-mTOR and FoxO1 signal pathways. We found that (1) WBV, E2 supplementation (E) and WBV combined with E2 supplementation (WBV+E) significantly increased serum estradiol content, quadriceps muscle mass and grip strength in ovariectomized mice, accompanied with alterations of body composition (reducing fat content, increasing lean body mass and lean percent), furthermore, the altered degrees of these indicators by WBV+E were greater than WBV alone; (2) WBV, E and WBV+E remarkably increased the activities of Akt and mTOR and decreased FoxO1 activity, and the changed degrees by WBV+E were greater than WBV alone; (3) Pearson correlation coefficient revealed that serum estradiol content was positively correlated with Akt and mTOR activities, while inversely associated with FoxO1 activity. We concluded that WBV could significantly increase muscle mass and strength in ovariectomized mice, which might achieve through activating Akt-mTOR and suppressing FoxO1 signal pathways, and the improving effect of WBV on muscle mass and strength was better when in the presence of estrogen.
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Estradiol , Estrógenos , Proteína Forkhead Box O1 , Fuerza Muscular , Ovariectomía , Serina-Treonina Quinasas TOR , Vibración , Animales , Femenino , Vibración/uso terapéutico , Ratones , Fuerza Muscular/fisiología , Serina-Treonina Quinasas TOR/metabolismo , Estradiol/sangre , Proteína Forkhead Box O1/metabolismo , Estrógenos/sangre , Estrógenos/metabolismo , Transducción de Señal , Composición Corporal/fisiología , Humanos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Músculo Esquelético/metabolismo , Músculo Esquelético/fisiología , Condicionamiento Físico Animal/fisiología , Condicionamiento Físico Animal/métodosRESUMEN
Insufficient energy intake to meet energy expenditure demands of physical activity can result in systemic neuroendocrine and metabolic abnormalities in activity-dependent anorexia and relative energy deficiency in sport (REDs). REDs affects >40% of athletes, yet the lack of underlying molecular changes has been a hurdle to have a better understanding of REDs and its treatment. To assess the molecular changes in response to energy deficiency, we implemented the "exercise-for-food" paradigm, in which food reward size is determined by wheel-running activity. By using this paradigm, we replicated several aspects of REDs in female and male mice with high physical activity and gradually reduced food intake, which results in weight loss, compromised bone health, organ-specific mass changes, and altered rest-activity patterns. By integrating transcriptomics of 19 different organs, we provide a comprehensive dataset that will guide future understanding of REDs and may provide important implications for metabolic health and (athletic) performance.
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Ratones Endogámicos C57BL , Transcriptoma , Animales , Ratones , Masculino , Femenino , Metabolismo Energético , Deficiencia Relativa de Energía en el Deporte/genética , Deficiencia Relativa de Energía en el Deporte/metabolismo , Condicionamiento Físico Animal , Modelos Animales de EnfermedadRESUMEN
Background: Exercise is recognized for its broad health benefits, influencing various physiological processes, including the behavior of adipose tissue macrophages (ATMs). While existing studies mainly associate ATM activity with obesity and metabolic syndrome, our study explores the impact of aerobic exercise on ATM microRNA expression profiling in a non-obese context, highlighting its general health-promoting mechanisms. Methods: Sixty male C57BL/6 mice were randomly assigned to either a sedentary (S) or an exercise (E) group. The S group remained inactive, while the E group underwent a one-week treadmill adaptation, followed by an 8-week aerobic treadmill exercise protocol (60 min/day, 5 days/week, at 65%-75% VO2max). Post-training, glucose tolerance and the serum lipid levels were measured in mice subjected to both exercise and non-exercise conditions. ATMs harvested from visceral adipose tissues were analyzed and sorted using flow cytometer. To further investigate the effects of exercise in ATMs at the molecular level, miRNA microarray analysis was performed, followed by bioinformatic analysis. Results: The 8-week regimen of moderate-intensity aerobic exercise ameliorated glucolipid metabolism and fostered a dynamic shift toward an M2 macrophage phenotype in the adipose tissue, independent of obesity. A total of 62 differentially expressed miRNAs were identified in ATMs of mice post-exercise. Notably, six miRNAs (miR-212-5p, miR-511-5p, miR-7b-5p, miR-142-3p, miR-1894-3p, and miR-31-5p) as well as their target gene were consistently altered and associated with macrophage polarization and metabolic regulation. Conclusion: Our findings broaden the understanding of how exercise regulates ATM functions through significant changes in microRNA profiles, emphasizing its potential to enhance health and prevent chronic conditions. This study supports the application of aerobic exercise for its preventive effects on chronic diseases and underscores the importance of microRNA profiling in understanding the immune-modulatory impacts of exercise.
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Tejido Adiposo , Perfilación de la Expresión Génica , Macrófagos , Ratones Endogámicos C57BL , MicroARNs , Condicionamiento Físico Animal , Animales , MicroARNs/genética , Macrófagos/metabolismo , Macrófagos/inmunología , Masculino , Ratones , Tejido Adiposo/metabolismo , Metabolismo de los Lípidos , TranscriptomaRESUMEN
Systemic arterial hypertension is accompanied by autonomic impairments that, if not contained, promotes cardiac functional and morphological damages. Pyridostigmine bromide (PYR) treatment results in positive effects on autonomic control and beneficial cardiac remodeling. These findings were also observed after aerobic physical training (APT). However, little is known about PYR effects on left ventricular contractility, mainly when it is combined with APT. We aimed to investigate the effects of chronic acetylcholinesterase inhibition on cardiac autonomic tone balance, coronary bed reactivity, and left ventricular contractility in spontaneously hypertensive rats (SHR) submitted to APT. Male SHR (18 weeks) were divided into two groups (N = 16): untrained and submitted to APT for 14 weeks (18th to 32nd week). Half of each group was treated with PYR (15 mg/kg/day) for two weeks (31st to 32nd week). The experimental protocol consisted of recording hemodynamic parameters, double autonomic blockade with atropine and propranolol, and assessment of coronary bed reactivity and ventricular contractility in isolated hearts using the Langendorff technique. PYR and APT reduced blood pressure, heart rate, and sympathetic influence on the heart. The Langendorff technique showed that APT increased coronary perfusion pressure and left ventricle contractility in response to coronary flow and ß-agonist administration. However, treatment with PYR annulled the effects of APT. In conclusion, although chronic treatment with PYR reduces cardiac sympathetic tonic influence, it does not favor coronary bed reactivity and cardiac contractility gains. PYR treatment in the trained SHR group nullified the coronary vascular reactivity and cardiac contractility gains.
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Inhibidores de la Colinesterasa , Hipertensión , Contracción Miocárdica , Condicionamiento Físico Animal , Bromuro de Piridostigmina , Ratas Endogámicas SHR , Animales , Inhibidores de la Colinesterasa/farmacología , Masculino , Ratas , Contracción Miocárdica/efectos de los fármacos , Hipertensión/tratamiento farmacológico , Hipertensión/fisiopatología , Bromuro de Piridostigmina/farmacología , Presión Sanguínea/efectos de los fármacos , Frecuencia Cardíaca/efectos de los fármacos , Hemodinámica/efectos de los fármacos , Vasos Coronarios/efectos de los fármacos , Vasos Coronarios/fisiopatología , Función Ventricular Izquierda/efectos de los fármacos , Acetilcolinesterasa/metabolismoRESUMEN
OBJECTIVE: To explore the mechanism underlying the therapeutic effect of Bufei Yishen Formula III combined with exercise rehabilitation (ECC-BYF III + ER) on chronic obstructive pulmonary disease (COPD) and further identify hub genes. MATERIALS AND METHODS: Gene Set Enrichment Analysis was used to identify the COPD-associated pathways and reversal pathways after ECC-BYF III + ER treatment. Protein-protein interaction network analysis and cytoHubba were used to identify the hub genes. These genes were verified using independent datasets, molecular docking and quantitative real-time polymerase chain reaction experiment. RESULTS: Using the high-throughput sequencing data of COPD rats from our laboratory, 49 significantly disturbed pathways were identified in COPD model compared with control group via gene set enrichment analysis (false discovery rate < 0.05). The 34 pathways were reversed after ECC-BYF III + ER treatment. In the 2306 genes of these 34 pathways, 121 of them were differentially expressed in COPD rats compared with control samples. A protein-protein interaction network comprising 111 nodes and 274 edges was created, and 34 candidate genes were identified. Finally, seven COPD hub genes (Il1b, Ccl2, Cxcl1, Apoe, Ccl7, Ccl12, and Ccl4) were well identified and verified in independent COPD rat data from our laboratory and the public dataset GSE178513. The area under the receiver operating characteristic curve values ranged from 0.86 to 1 and from 0.67 to 1, respectively. The reliability of the mentioned genes, which can bind to the active ingredients of ECC-BYF III through molecular docking, were further verified through qRT-PCR experiments. CONCLUSION: Thirty-four COPD-related pathways and seven hub genes that may be regulated by ECC-BYF III + ER were identified and well verified. The findings of this study may provide insights into the treatment and mechanism underlying COPD.
GSEA method can circumvent the limitations of the preacquisition of DEGs for ORA and is suitable for small sample data.34 COPD-related pathways that can be regulated by ECC-BYF III + ER were identified.Seven COPD hub genes were identified and well verified in independent RNA-seq data and PCR experiment, and they may play a crucial role in TCM treatment.
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Medicamentos Herbarios Chinos , Simulación del Acoplamiento Molecular , Mapas de Interacción de Proteínas , Enfermedad Pulmonar Obstructiva Crónica , Enfermedad Pulmonar Obstructiva Crónica/genética , Enfermedad Pulmonar Obstructiva Crónica/rehabilitación , Animales , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Ratas , Masculino , Modelos Animales de Enfermedad , Terapia por Ejercicio/métodos , Condicionamiento Físico Animal , Ratas Sprague-Dawley , Terapia CombinadaRESUMEN
Despite the already dire impact of pancreatic cancer, a growing subset of patients with obesity exhibits an amplified risk of disease and worse outcomes. Mouse models have revealed that obesity is distinctly pathogenic, accelerating pancreatic ductal adenocarcinoma (PDAC) progression and inducing increased desmoplasia and myeloid cell infiltration in the tumor microenvironment. However, whether and how obesity-countering interventions, such as exercise, reverse the protumorigenic effects of obesity is incompletely understood. In this issue of Cancer Research, Pita-Grisanti and colleagues investigate the impact of physical activity (PA) in disrupting obesity-driven PDAC. Employing a variety of sophisticated models, including autochthonous genetically engineered mice, orthotopic syngeneic allografts, high-fat diet-induced obesity, and PA interventions in mice and humans, the authors found that PA impedes PDAC development in obese mice but does not impact the growth of advanced tumors. These antitumor effects correlated with reduced inflammation and fibrosis in the tumor microenvironment, a decline in high-fat diet-induced circulating inflammatory cytokines, and an increase in the IL15 signaling axis in white adipose tissue. Although adipose-targeted IL15 therapy was effective in suppressing advanced tumor growth in lean mice, obese mice were resistant to its therapeutic benefits. Together, the findings argue that PA delays obesity-driven early PDAC progression, implicating the preferential benefit of exercise as a preventative strategy. They further identify changes in obesity-associated local and systemic cytokine production as a possible mechanism for the antitumor effects of PA and help define context-specific determinants of response for emerging IL15-based immunotherapies. See related article by Pita-Grisanti et al., p. 3058.
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Carcinoma Ductal Pancreático , Obesidad , Neoplasias Pancreáticas , Microambiente Tumoral , Animales , Obesidad/complicaciones , Obesidad/metabolismo , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/prevención & control , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/etiología , Humanos , Ratones , Carcinoma Ductal Pancreático/patología , Carcinoma Ductal Pancreático/prevención & control , Carcinoma Ductal Pancreático/metabolismo , Ejercicio Físico/fisiología , Condicionamiento Físico Animal , Dieta Alta en Grasa/efectos adversos , Modelos Animales de EnfermedadRESUMEN
Aerobic exercise has many effects on brain function, particularly at the hippocampus. Exercise has been shown to increase the rate of adult neurogenesis within the dentate gyrus and decrease the density of perineuronal nets in area CA1. The relationship between the rate of neurogenesis and the density of perineuronal nets in CA1 is robust; however, these studies only ever examined these effects across longer time scales, with running manipulations of 4 weeks or longer. With such long periods of manipulation, the precise temporal nature of the relationship between running-induced neurogenesis and reduced perineuronal net density in CA1 is unknown. Here, we provided male and female mice with home cage access to running wheels for 0, 1, 2, or 4 weeks and quantified hippocampal neurogenesis and CA1 perineuronal net density. In doing so, we observed a 2-week delay period prior to the increase in neurogenesis, which coincided with the same delay prior to decreased CA1 perineuronal net density. These results highlight the closely linked temporal relationship between running-induced neurogenesis and decreased perineuronal net expression in CA1.
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Región CA1 Hipocampal , Ratones Endogámicos C57BL , Neurogénesis , Carrera , Animales , Masculino , Carrera/fisiología , Femenino , Región CA1 Hipocampal/fisiología , Factores de Tiempo , Red Nerviosa/fisiología , Condicionamiento Físico Animal , RatonesRESUMEN
Our previous studies have demonstrated that konjac glucomannan (KGM) can prevent dysbiosis induced by antibiotics. While exercise may also impact the gut microbiome, there are limited studies reporting its protective effect on antibiotic-induced dysbiosis. Therefore, this study investigated the preventive and regulatory effects of a combination of 6-week exercise and KGM intervention on antibiotic-induced dysbiosis in C57BL/6J mice compared with a single intervention. The results showed that combined exercise and KGM intervention could restore the changes in the relative abundance of Bacteroides (3.73% with CTL versus 14.23% with ATBX versus 4.46% with EK) and Prevotellaceae_Prevotella (0.33% with CTL versus 0.00% with ATBX versus 0.30% with EK) induced by antibiotics (p < 0.05), and minimized the Bray-Curtis distance induced by antibiotics (0.55 with CTL versus 0.81 with ATBX versus 0.80 with EXC versus 0.83 with KGM versus 0.75 with EK). Compared with the combined intervention, exercise intervention also produced a certain level of recovery effects; the relative abundance of Rikenellaceae (1.96% with CTL versus 0.09% with ATBX versus 0.49% with EXC) was restored, while KGM supplementation showed the best preventive effect. In addition, the combination of exercise and KGM significantly enriched microbial purine metabolic pathways (p < 0.05). These findings indicate that combining exercise with KGM could be a promising approach to reducing the side effects of antibiotics on the gut microbiome.
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Antibacterianos , Disbiosis , Microbioma Gastrointestinal , Mananos , Ratones Endogámicos C57BL , Condicionamiento Físico Animal , Animales , Mananos/farmacología , Disbiosis/prevención & control , Disbiosis/inducido químicamente , Antibacterianos/farmacología , Antibacterianos/efectos adversos , Microbioma Gastrointestinal/efectos de los fármacos , Ratones , Masculino , Terapia CombinadaRESUMEN
6'-Sialyllactose (6'-SL), found in human breast milk, exhibits anti-inflammatory, immune function-enhancing, brain development-promoting, and gut health-improving effects. However, its effects on muscle fatigue remain unknown. Here, we aimed to investigate the effects of 6'-SL on blood lactate level, muscle fiber type, and oxidative phosphorylation protein complexes (OXPHOS) in muscle after exercise using C57BL/6J male mice. C57BL/6J mice were randomly assigned to control or 100 mg/kg 6'-SL. After 12 weeks of 6'-SL administration, the mice were made to perform treadmill exercise; their blood lactate and glucose levels were measured at the basal level (rest) and 0, 5, and 10 min after treadmill exercise. Results showed that 6'-SL treatment in C57BL/6J mice significantly reduced blood lactate level and improved blood glucose level. Moreover, 6'-SL increased the expression of slow-myosin heavy chain (MHC) and OXPHOS in gastrocnemius muscle. In addition, 6'-SL treatment for 12 weeks did not affect food intake, serum biomarkers of tissue injury, and lipid profiles compared with those of the controls. These findings indicate that non-toxic 6'-SL suppressed muscle fatigue during exercise by promoting protein expression of muscle fibers, especially slow-twitch muscle fibers characterized by abundant OXPHOS complexes and decreased blood lactate level. This study suggests that 6'-SL holds promise as a nutritional supplement in exercise and clinical settings, subject to further validation.
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Ácido Láctico , Ratones Endogámicos C57BL , Fatiga Muscular , Músculo Esquelético , Condicionamiento Físico Animal , Animales , Masculino , Ácido Láctico/sangre , Ratones , Fatiga Muscular/efectos de los fármacos , Músculo Esquelético/metabolismo , Músculo Esquelético/efectos de los fármacos , Lactosa/análogos & derivados , Lactosa/farmacología , Glucemia/metabolismo , Glucemia/efectos de los fármacosRESUMEN
The present study aimed to investigate age-related changes in histone variant H3.3 and its role in the aging process of mouse tibialis anterior muscle. H3.3 level significantly increased with age and correlated with H3K27me3 level. Acute exercise successfully upregulated the target gene expression in 8-wk-old mice, whereas no upregulation was noted in 53-wk-old mice. H3K27me3 level was increased at these loci in response to acute exercise in 8-wk-old mice. However, in 53-wk-old mice, H3.3 and H3K27me3 levels were increased at rest and were not affected by acute exercise. Furthermore, forced H3.3 expression in the skeletal muscle of 8-wk-old mice led to a gradual improvement in motor function. The results suggest that age-related H3.3 accumulation induces the formation of repressive chromatin in the mouse tibialis anterior muscle. However, H3.3 accumulation also appears to play a positive role in enhancing skeletal muscle function.
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Envejecimiento , Cromatina , Histonas , Músculo Esquelético , Animales , Histonas/metabolismo , Músculo Esquelético/metabolismo , Ratones , Envejecimiento/metabolismo , Envejecimiento/fisiología , Cromatina/metabolismo , Masculino , Condicionamiento Físico Animal/fisiología , Ratones Endogámicos C57BLRESUMEN
Doxorubicin (DOX) is a potent chemotherapeutic agent with well-documented dose-dependent cardiotoxicity. Regular exercise is recognized for its cardioprotective effects against DOX-induced cardiac inflammation, although the precise mechanisms remain incompletely understood. The activation of inflammasomes has been implicated in the pathogenesis and treatment of DOX-induced cardiotoxicity, with the nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome emerging as a key mediator in cardiovascular inflammation. This study aimed to investigate the role of exercise in modulating the NLRP3 inflammasome to protect against DOX-induced cardiac inflammation. Male Sprague-Dawley rats were randomly assigned to receive a 10-day course of DOX or saline injections, with or without a preceding 10-week treadmill running regimen. Cardiovascular function and histological changes were subsequently evaluated. DOX-induced cardiotoxicity was characterized by cardiac atrophy, systolic dysfunction, and hypotension, alongside activation of the NLRP3 inflammasome. Our findings revealed that regular exercise preserved cardiac mass and hypertrophic indices and prevented DOX-induced cardiac dysfunction, although it did not fully preserve blood pressure. These results underscore the significant cardioprotective effects of exercise against DOX-induced cardiotoxicity. While regular exercise did not entirely prevent DOX-induced hypotension, our findings demonstrate that it confers protection against DOX-induced cardiotoxicity by suppressing NLRP3 inflammasome activation in the heart, underscoring its anti-inflammatory role. Further research should explore the temporal dynamics and interactions among exercise, pyroptosis, and other pathways in DOX-induced cardiotoxicity to enhance translational applications in cardiovascular medicine.
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Cardiomiopatías , Modelos Animales de Enfermedad , Doxorrubicina , Inflamasomas , Proteína con Dominio Pirina 3 de la Familia NLR , Condicionamiento Físico Animal , Ratas Sprague-Dawley , Animales , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Doxorrubicina/efectos adversos , Ratas , Masculino , Inflamasomas/metabolismo , Cardiomiopatías/inducido químicamente , Cardiomiopatías/metabolismo , Cardiotoxicidad/metabolismo , Cardiotoxicidad/prevención & controlRESUMEN
To improve exercise performance, the supplement of nutrients has become a common practice before prolonged exercise. Trimethylamine N-oxide (TMAO) has been shown to ameliorate oxidative stress damage, which may be beneficial in improving exercise capacity. Here, we assessed the effects of TMAO on mice with exhaustive swimming, analyzed the metabolic changes, and identified significantly altered metabolic pathways of skeletal muscle using a nuclear magnetic resonance-based (NMR-based) metabolomics approach to uncover the effects of TMAO improving exercise performance of mice. We found that TMAO pre-administration markedly prolonged the exhaustive time in mice. Further investigation showed that TMAO pre-administration increased levels of 3-hydroxybutyrate, isocitrate, anserine, TMA, taurine, glycine, and glutathione and disturbed the three metabolic pathways related to oxidative stress and protein synthesis in skeletal muscle. Our results provide a metabolic mechanistic understanding of the effects of TMAO supplements on the exercise performance of skeletal muscle in mice. This work may be beneficial in exploring the potential of TMAO to be applied in nutritional supplementation to improve exercise performance. This work will lay a scientific foundation and be beneficial to exploring the potential of TMAO to apply in nutritional supplementation.
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Metabolómica , Metilaminas , Músculo Esquelético , Condicionamiento Físico Animal , Animales , Metilaminas/metabolismo , Metilaminas/farmacología , Ratones , Metabolómica/métodos , Músculo Esquelético/metabolismo , Músculo Esquelético/efectos de los fármacos , Masculino , Metaboloma/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Espectroscopía de Protones por Resonancia Magnética , NataciónRESUMEN
BACKGROUND: Chronic Chagas cardiomyopathy (CCC) is caused by an inflammatory process induced by Trypanosoma cruzi, which leads to myocarditis with reactive and reparative fibrosis. CCC progresses with myocardial perfusion abnormalities and histopathological events that affect cardiorespiratory fitness (CRF). OBJECTIVES: We evaluated the effects of aerobic physical training (APT) on myocardial perfusion and on morphological and functional impairments related with inflammation and fibrosis in Syrian hamsters with CCC. As a secondary objective, we analyzed the cross-sectional areas of the skeletal muscle. METHODS: Hamsters with CCC and their respective controls were divided into four groups: CCC sedentary, CCC-APT, sedentary control and APT control. Seven months after infection, the animals underwent echocardiography, myocardial perfusion scintigraphy and cardiopulmonary exercise testing. Moderate-intensity APT was performed for fifty minutes, five times a week, for eight weeks. Subsequently, the animals were reassessed. Histopathological analysis was conducted after the above-mentioned procedures. The level of significance was set at 5% in all analyses (p<0.05). RESULTS: CCC sedentary animals presented worse myocardial perfusion defects (MPD) over time, reduced left ventricle ejection fraction (LVEF) and showed more inflammation and fibrosis when compared to other groups (mixed ANOVA analysis). Conversely, APT was able to mitigate the progression of MPD, ameliorate inflammation and fibrosis and improve CRF efficiency in CCC-APT animals. CONCLUSIONS: Our study demonstrated that APT ameliorated cardiac dysfunction, MPD, and reduced inflammation and fibrosis in CCC hamster models. Additionally, CCC-SED animals presented skeletal muscle atrophy while CCC-APT animals showed preserved skeletal muscle CSA. Understanding APT's effects on CCC's pathophysiological dimensions is crucial for future research and therapeutic interventions.
FUNDAMENTO: A Cardiomiopatia Chagásica Crônica (CCC) é causada por um processo inflamatório induzido pelo Trypanosoma cruzi, que leva à miocardite com fibrose reativa e reparativa. A CCC progride com alterações de perfusão miocárdica e eventos histopatológicos que afetam a Aptidão Cardiorrespiratória (ACR). OBJETIVOS: Avaliamos os efeitos do Treinamento Físico Aeróbico (TFA) na perfusão miocárdica e nos comprometimentos morfológicos e funcionais relacionados à inflamação e fibrose em hamsters sírios com CCC. Como objetivo secundário, analisamos as áreas de secção transversa do músculo esquelético. MÉTODOS: Hamsters com CCC e seus respectivos controles foram divididos em quatro grupos: CCC sedentário, CCC-TFA, controle sedentário e controle TFA. Sete meses após a infecção, os animais foram submetidos à ecocardiografia, à cintilografia de perfusão miocárdica e ao teste de esforço cardiopulmonar. TFA de intensidade moderada foi realizado durante cinquenta minutos, cinco vezes por semana, por oito semanas. Posteriormente, os animais foram reavaliados. A análise histopatológica foi realizada após os procedimentos acima mencionados. O nível de significância foi estabelecido em 5% em todas as análises (p<0,05). RESULTADOS: Animais com CCC sedentários apresentaram piores Defeitos de Perfusão Miocárdica (DPM) ao longo do tempo, Fração de Ejeção do Ventrículo Esquerdo (FEVE) reduzida, e apresentaram mais inflamação e fibrose quando comparados aos demais grupos (análise ANOVA mista). Por outro lado, o TFA foi capaz de mitigar a progressão do DPM, atenuar a inflamação e a fibrose e melhorar a eficiência da ACR em animais CCC-TFA. CONCLUSÃO: Nosso estudo demonstrou que o TFA melhorou a disfunção cardíaca, DPM e reduziu a inflamação e a fibrose em modelos de hamster com CCC. Além disso, os animais CCC-SED apresentaram atrofia do músculo esquelético, enquanto os animais CCC-TFA apresentaram a AST do músculo esquelético preservada. Compreender os efeitos da TFA nas dimensões fisiopatológicas da CCC é crucial para futuras pesquisas e intervenções terapêuticas.
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Cardiomiopatía Chagásica , Modelos Animales de Enfermedad , Fibrosis , Condicionamiento Físico Animal , Animales , Cardiomiopatía Chagásica/fisiopatología , Cardiomiopatía Chagásica/terapia , Condicionamiento Físico Animal/fisiología , Enfermedad Crónica , Masculino , Miocardio/patología , Ecocardiografía , Cricetinae , Inflamación , Factores de Tiempo , Mesocricetus , Músculo Esquelético/fisiopatología , Músculo Esquelético/patología , Prueba de Esfuerzo , Imagen de Perfusión Miocárdica/métodos , Reproducibilidad de los Resultados , Miocarditis/fisiopatología , Miocarditis/terapiaRESUMEN
OBJECTIVE: Glucagon-like peptide-1 (GLP1) and leptin (Lep) are afferent signals that regulate energy metabolism. Lactational hypernutrition results in hyperphagia and adiposity in adult life, and these events can be prevented by exercise. We evaluated the effects of swimming training on hypothalamic (GLP1-R) and Lep receptor (Lep-R) gene expressions in lactational hypernutrition-induced obesity. METHODS: On the 3rd postnatal day, the litter sizes of lactating dams were adjusted to small litters (SL; 3 pups/dams) or normal litters (NL; 9 pups/dams). After weaning (21 days), NL and SL male rats were randomly distributed to sedentary (Sed) and exercised (Exe) groups. Exercised mice swam (30 min/3 times/week) for 68 days. Food intake and body weight gain were registered. At 92 days, intraperitoneal glucose and insulin tolerance tests were performed and rats were euthanized at 93 days; adipose tissue depots were weighed, and blood counts and plasma biochemical analyses performed. Hypothalamus were isolated to evaluate Lep-R and GLP1-R gene expressions. RESULTS: Small litters sedentary rats presented increased body weight gain, adiposity, insulin sensibility and higher fasting values of glucose and triglycerides, besides higher hypothalamic gene expressions of Lep-R and GLP1-R, compared to NLSed animals. SLExe rats did not develop obesity or metabolic abnormalities and Lep-R and GLP1-R hypothalamic gene expressions were normalized. CONCLUSION: Lactational hypernutrition induces obesity and metabolic dysfunction in adult life, in association with higher hypothalamic expressions of the Lep-R and GLP1-R genes. Exercise prevented obesity and improved metabolic state in SL overnourished rats, and normalized their hypothalamic Lep-R and GLP1-R gene expressions.
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Hipotálamo , Obesidad , Condicionamiento Físico Animal , Ratas Wistar , Receptores de Leptina , Natación , Animales , Hipotálamo/metabolismo , Obesidad/metabolismo , Obesidad/genética , Obesidad/prevención & control , Condicionamiento Físico Animal/fisiología , Condicionamiento Físico Animal/métodos , Masculino , Receptores de Leptina/genética , Receptores de Leptina/metabolismo , Femenino , Natación/fisiología , Tamaño de la Camada , Receptor del Péptido 1 Similar al Glucagón/metabolismo , Receptor del Péptido 1 Similar al Glucagón/genética , Ratas , Lactancia/metabolismo , Lactancia/fisiología , Péptido 1 Similar al Glucagón/metabolismo , Leptina/sangre , Leptina/metabolismo , Distribución Aleatoria , Expresión Génica , Ingestión de Alimentos/fisiología , Adiposidad/fisiologíaRESUMEN
Skeletal muscle is a highly heterogeneous tissue, and its contractile proteins are composed of different isoforms, forming various types of muscle fiber, each of which has its own metabolic characteristics. It has been demonstrated that endurance exercise induces the transition of muscle fibers from fast-twitch to slow-twitch muscle fiber type. Herein, we discover a novel epigenetic mechanism for muscle contractile property tightly coupled to its metabolic capacity during muscle fiber type transition with exercise training. Our results show that an 8-week endurance exercise induces histone methylation remodeling of PGC-1α and myosin heavy chain (MHC) isoforms in the rat gastrocnemius muscle, accompanied by increased mitochondrial biogenesis and an elevated ratio of slow-twitch to fast-twitch fibers. Furthermore, to verify the roles of reactive oxygen species (ROS) and AMPK in exercise-regulated epigenetic modifications and muscle fiber type transitions, mouse C2C12 myotubes were used. It was shown that rotenone activates ROS/AMPK pathway and histone methylation enzymes, which then promote mitochondrial biogenesis and MHC slow isoform expression. Mitoquinone (MitoQ) partially blocking rotenone-treated model confirms the role of ROS in coupling mitochondrial biogenesis with muscle fiber type. In conclusion, endurance exercise couples mitochondrial biogenesis with MHC slow isoform by remodeling histone methylation, which in turn promotes the transition of fast-twitch to slow-twitch muscle fibers. The ROS/AMPK pathway may be involved in the regulation of histone methylation enzymes by endurance exercise.
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Histonas , Cadenas Pesadas de Miosina , Biogénesis de Organelos , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma , Condicionamiento Físico Animal , Especies Reactivas de Oxígeno , Animales , Histonas/metabolismo , Ratones , Ratas , Especies Reactivas de Oxígeno/metabolismo , Masculino , Cadenas Pesadas de Miosina/metabolismo , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/metabolismo , Metilación , Fibras Musculares Esqueléticas/metabolismo , Epigénesis Genética , Fibras Musculares de Contracción Lenta/metabolismo , Resistencia Física/fisiología , Fibras Musculares de Contracción Rápida/metabolismo , Músculo Esquelético/metabolismo , Línea Celular , Proteínas Quinasas Activadas por AMP/metabolismoRESUMEN
Prolonged strenuous exercise induces oxidative stress, leading to oxidative damage, skeletal muscle fatigue, and reduced exercise performance. The body compensates for oxidative stress through antioxidant actions, while related enzymes alone may not overcome excessive oxidative stress during prolonged strenuous exercise. Phycocyanin is an important antioxidant supplement derived from blue-green algae, which may be helpful in this type of situation. This study determined the effects of phycocyanin on exercise performance from prolonged strenuous exercise. Forty Sprague Dawley male rats were divided into 5 groups (n = 8 /group); Control group (C), Exercise group (E), and Exercise with supplement groups receiving low dose (Phycocyanin = 100 mg/kg BW; ELP) and high dose (Phycocyanin = 200 mg/kg BW; EHP) or vitamin C (Vitamin C = 200 mg/kg BW; VC). Phycocyanin was found to decrease oxidative damage markers, muscle fatigue, and muscle atrophy through the activated AKT/mTOR pathway. This was also found to have greater increases in antioxidants via Nrf2 signaling and increases ATP synthesis, GLUT4 transporters, and insulin signaling due to increased IRS-1/AKT signaling. In conclusion, phycocyanin was found to reduce oxidative damage and muscle atrophy, including an increase in insulin signaling in skeletal muscles leading to increased exercise performance in rats.
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Músculo Esquelético , Factor 2 Relacionado con NF-E2 , Estrés Oxidativo , Ficocianina , Condicionamiento Físico Animal , Proteínas Proto-Oncogénicas c-akt , Ratas Sprague-Dawley , Transducción de Señal , Serina-Treonina Quinasas TOR , Animales , Estrés Oxidativo/efectos de los fármacos , Masculino , Factor 2 Relacionado con NF-E2/metabolismo , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Serina-Treonina Quinasas TOR/metabolismo , Transducción de Señal/efectos de los fármacos , Ratas , Ficocianina/farmacología , Proteínas Sustrato del Receptor de Insulina/metabolismo , Fatiga Muscular/efectos de los fármacos , Antioxidantes/metabolismo , Antioxidantes/farmacologíaRESUMEN
Xi-Kun Yuan Pin-Shi Ni Zhen-Hao Yan Zhi Yu Zhuang-Zhi Wang Chen-Kai Zhang Fang-Hui Li Xiao-Ming Yu 1Sports Department, Nanjing University of Science and Technology ZiJin College, Nanjing, China, 2School of Sport Sciences, Nanjing Normal University, Nanjing, China, 3Shanghai Seventh People's Hospital, Shanghai, China To investigate the effects of life-long exercise (LLE) on age-related inflammatory cytokines, apoptosis, oxidative stress, ferroptosis markers, and the NRF2/KAEP 1/Klotho pathway in rats. Eight-month-old female Sprague-Dawley rats were divided into four groups: 1) LLE: 18-month LLE training starting at 8 months of age, 2) Old moderate-intensity continuous training (OMICT): 8 months of moderate-intensity continuous training starting at 18 months of age, 3) Adult sedentary (ASED): 8 month-old adult sedentary control group, and 4) Old sedentary (OSED): a 26-month-old sedentary control group. Hematoxylin eosin staining was performed to observe the pathological changes of kidney tissue injury in rats; Masson's staining to observe the deposition of collagen fibers in rat kidney tissues; and western blotting to detect the expression levels of IL-6, IL 1beta, p53, p21, TNF-alpha, GPX4, KAEP 1, NRF2, SLC7A11, and other proteins in kidney tissues. Results: Compared with the ASED group, the OSED group showed significant morphological changes in renal tubules and glomeruli, which were swollen and deformed, with a small number of inflammatory cells infiltrated in the tubules. Compared with the OSED group, the expression levels of inflammation-related proteins such as IL-1beta, IL-6, TNF alpha, and MMP3 were significantly lower in the LLE group. Quantitative immunofluorescence analysis and western blotting revealed that compared with the ASED group, KAEP 1 protein fluorescence intensity and protein expression levels were significantly enhanced, while Klotho and NRF2 protein fluorescence intensity and protein expression levels were reduced in the OSED group. Compared with the OSED group, KAEP 1 protein fluorescence intensity and protein expression levels were reduced in the LLE and OMICT groups. Klotho and KAEP 1 protein expression levels and immunofluorescence intensity were higher in the LLE group than in the OSED group. The expression levels of GPX4 and SLC7A11, two negative marker proteins associated with ferroptosis, were significantly higher in the LLE group than in the OSED group, while the expression of p53 a cellular senescence-associated protein that negatively regulates SLC7A11, and the downstream protein p21 were significantly decreased. LLE may ameliorated aging-induced oxidative stress, inflammatory response, apoptosis, and ferroptosis by regulating Klotho and synergistically activating the NRF2/KAEP 1 pathway. Keywords: Life-long exercise, Moderate intensity continuous training, Aging, Kidney tissue, Ferroptosis.
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Apoptosis , Ferroptosis , Riñón , Proteínas Klotho , Factor 2 Relacionado con NF-E2 , Estrés Oxidativo , Condicionamiento Físico Animal , Ratas Sprague-Dawley , Animales , Factor 2 Relacionado con NF-E2/metabolismo , Estrés Oxidativo/fisiología , Femenino , Apoptosis/fisiología , Ratas , Ferroptosis/fisiología , Riñón/metabolismo , Riñón/patología , Condicionamiento Físico Animal/fisiología , Envejecimiento/metabolismo , Envejecimiento/patología , Inflamación/metabolismo , Inflamación/patología , Transducción de Señal/fisiología , Glucuronidasa/metabolismo , Biomarcadores/metabolismoRESUMEN
Recent studies suggest that lactate intake has a positive effect on glycogen recovery after exercise. However, it is important to verify the effect of lactate supplementation alone and the timing of glycogen recovery. Therefore, in this study, we aimed to examine the effect of lactate supplementation immediately after exercise on glycogen recovery in mice liver and skeletal muscle at 1, 3, and 5 h after exercise. Mice were randomly divided into the sedentary, exercise-only, lactate, and saline-treated groups. mRNA expression and activation of glycogen synthesis and lactate transport-related factors in the liver and skeletal muscle were assessed using real-time polymerase chain reaction. Skeletal muscle glycogen concentration showed an increasing trend in the lactate group compared with that in the control group at 3 and 5 h after post-supplementation. Additionally, exogenous lactate supplementation significantly increased the expression of core glycogen synthesis enzymes, lactate transporters, and pyruvate dehydrogenase E1 alpha 1 in the skeletal muscles. Conversely, glycogen synthesis, lactate transport, and glycogen oxidation to acetyl-CoA were not significantly affected in the liver by exogenous lactate supplementation. Overall, these results suggest that post-exercise lactate supplement enables glycogen synthesis and recovery in skeletal muscles.
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Glucógeno , Ácido Láctico , Hígado , Condicionamiento Físico Animal , Animales , Glucógeno/metabolismo , Ácido Láctico/metabolismo , Condicionamiento Físico Animal/fisiología , Masculino , Hígado/metabolismo , Hígado/efectos de los fármacos , Ratones , Músculo Esquelético/metabolismo , Músculo Esquelético/efectos de los fármacos , Ratones Endogámicos C57BL , Transportadores de Ácidos Monocarboxílicos/metabolismoRESUMEN
The present study aimed to explore the effect of swimming exercise on vascular calcification in type 2 diabetic rats and its related molecular mechanism. Male Sprague Dawley (SD) rats were randomly divided into normal control (NC), diabetes control (DC) and diabetes+exercise (DE) groups. The DC and DE groups were intraperitoneally injected with streptozotocin (STZ) and fed with high-fat diet to establish type 2 diabetes mellitus model. The NC and DC groups did not exercise, and the DE group performed swimming exercise for 8 weeks. ELISA was used to detect the serum glycated hemoglobin A1c (HbA1c) level. The aortas of rats were taken as sample. Assay kits were used to detect vascular calcium content and alkaline phosphatase (ALP) activity. Von Kossa staining was used to detect calcium deposition. qRT-PCR was used detect the expression of microRNA-145 (miR-145). Western blot was used to detect the protein expression levels of smooth muscle contraction markers, calcification marker and related proteins. The results showed that, compared with the NC group, the blood glucose, serum HbA1c level, vascular calcium content and ALP activity in the DC group were significantly increased, the protein expression levels of smooth muscle contraction markers smooth muscle protein 22α (SM22α) and α-smooth muscle actin (α-SMA) were significantly down-regulated, and the protein expression level of calcification marker osteopontin (OPN) was significantly up-regulated; Compared with the DC group, the serum HbA1c level, vascular calcium content and ALP activity in the DE group were significantly decreased, the protein expression levels of SM22α and α-SMA were significantly up-regulated, and the protein expression level of OPN was significantly down-regulated; Compared with the NC group, the expression of miR-145-5p in the DC group was significantly down-regulated, and the protein expression levels of transforming growth factor-ß (TGF-ß), SMAD2, ERK1/2 and p-ERK1/2 were significantly up-regulated; Compared with the DC group, the expression of miR-145-5p was significantly up-regulated in the DE group, while the expressions of TGF-ß, ERK1/2 and p-ERK1/2 were significantly down-regulated. These results suggest that miR-145/TGF-ß signaling is involved in the improving effects of 8-week swimming exercise on glucose metabolism disorder, vascular smooth muscle cell phenotype switching and vascular calcification in type 2 diabetes mellitus.
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Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , MicroARNs , Condicionamiento Físico Animal , Ratas Sprague-Dawley , Natación , Calcificación Vascular , Animales , Masculino , Ratas , MicroARNs/metabolismo , MicroARNs/genética , Calcificación Vascular/metabolismo , Calcificación Vascular/etiología , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Experimental/metabolismo , Natación/fisiología , Factor de Crecimiento Transformador beta/metabolismoRESUMEN
This paper aimed to investigate the effects of exercise on hepatic platelet-activating factor (PAF) metabolism in rats fed a high-fat diet. Thirty-two male Sprague-Dawley (SD) rats were divided into control group (C), high-fat diet group (H), exercise group (EC), and high-fat diet+exercise group (EH). Serum lipids, glucose, insulin and markers of hepatic injury after a 16-week dietary and/or exercise intervention (60 min/day, 6 times/week) were measured by biochemical analysis; liver lipidomic profiles were analyzed by liquid chromatograph-mass spectrometer (LC-MS). Gene and protein expression of enzymes related to PAF metabolism were determined by qPCR and Western blot respectively. The results showed that high-fat diet feeding significantly increased the levels of low-density lipoprotein-cholesterol (LDL-C) and liver injury markers including purine nucleoside phosphorylase (PNP) and malondialdehyde (MDA) in rats, which were decreased by exercise. Furthermore, high-fat diet feeding significantly increased the hepatic PAF content, which was also attenuated by exercise. In addition, although high-fat diet treatment resulted in an increase in the expression of both PAF synthetase (PAF-CPT and PLA2) and hydrolase (Lp-PLA2 and PAF-AH(II)), induction of PAF synthetase was much greater than that of PAF hydrolase. While exercise increased the expression of Lp-PLA2 and PAF-AH(II) and decreased the expression of PAF-CPT and PLA2, key PAF synthesizing enzymes. In conclusion, high-fat diet-induced increase in hepatic PAF content is mainly due to the increase of its pathological synthesis at the translational level. Exercise reduces hepatic PAF content in high-fat fed rats by increasing PAF hydrolysis and decreasing its synthesis.