RESUMO
The objective of this exploratory study was to assess the changes on lipidome and metabolome profiling of Longissimus lumborum bull muscle with different ultimate pH (pHu) and aging periods. The bull muscles classified as normal, intermediate, or high pHu were collected from a Brazilian commercial slaughterhouse, cut into steaks, individually vacuum-packaged, and aged for 3 days (3-d) or 21 days (21-d) at 2 °C. Muscle extracts were analyzed for the profiles of both lipids, by mass spectrometry (via direct flow-injection), and metabolites, by nuclear magnetic resonance, with downstream multivariate data analysis. As major results, pairwise comparisons identified C12:0 and C14:0 acylcarnitines as potential biomarkers of the intermediate pHu-muscle, which are related to lipid catabolism for alternative energy metabolism and indicate less protein breakage postmortem. Interestingly, the concentration of arginine at early postmortem aging (3-d) may influence the previously reported improved tenderness in normal and high pHu-muscles. Moreover, upregulation of fumarate, formate, and acetate with increased pHu muscle at 21-d aging indicate more intense tricarboxylic acid cycle, amino acid degradation, and pyruvate oxidation by reactive oxygen species, respectively. These three compounds (fumarate, formate, and acetate) discriminated statistically the muscle with high pHu at 21-d aging. The normal pHu-muscle showed higher concentrations of glycogenolysis and glycolysis metabolites, including glucose, mannose, and pyruvate. Hence, our results enhance knowledge of postmortem biochemical changes of beef within different pHu groups aged up to 21 days, which is essential to understand the mechanisms underpinning bull meat quality changes.
Assuntos
Metaboloma , Músculo Esquelético , Carne Vermelha , Animais , Bovinos , Carne Vermelha/análise , Músculo Esquelético/química , Músculo Esquelético/metabolismo , Concentração de Íons de Hidrogênio , Masculino , Lipidômica/métodos , Mudanças Depois da Morte , Brasil , Manipulação de Alimentos/métodos , Formiatos , Carnitina/análogos & derivados , Carnitina/metabolismo , Carnitina/análiseRESUMO
This study aimed to evaluate the influence of combined intermittent fasting (IF) and high-intensity interval training (HIIT) on morphology, caspase-independent apoptosis signaling pathway, and myostatin expression in soleus and gastrocnemius (white portion) muscles from healthy rats. Sixty-day-old male Wistar rats (n = 60) were divided into four groups: control (C), IF, high-intensity-interval training (T), and high-intensity-interval training and intermittent fasting (T-IF). The C and T groups received ad libitum chow daily; IF and T-IF received the same standard chow every other day. Animals from T and T-IF underwent a HIIT protocol five times a week for 12 weeks. IF reduced gastrocnemius mass and increased pro-apoptotic proteins apoptosis-inducing factor (AIF) and endonuclease G (EndoG) in soleus and cleaved-to-non-cleaved PARP-1 ratio and myostatin expression in gastrocnemius white portion. HIIT increased AIF and apoptosis repressor with caspase recruitment domain expression in soleus and cleaved-to-total PARP-1 ratio in gastrocnemius muscle white portion. The combination of IF and HIIT reduced fiber cross-sectional area in both muscles, increased EndoG and AIF expression, and decreased cleaved-to-non-cleaved PARP-1 ratio in gastrocnemius muscle white portion. Muscle responses to IF and HIIT are directly impacted by the muscle fiber type composition and are modulated, at least in part, by myostatin and caspase-independent apoptosis signaling.
Assuntos
Fator de Indução de Apoptose , Apoptose , Jejum , Treinamento Intervalado de Alta Intensidade , Fibras Musculares de Contração Lenta , Atrofia Muscular , Miostatina , Ratos Wistar , Transdução de Sinais , Animais , Masculino , Apoptose/fisiologia , Jejum/metabolismo , Jejum/fisiologia , Miostatina/metabolismo , Treinamento Intervalado de Alta Intensidade/métodos , Ratos , Transdução de Sinais/fisiologia , Atrofia Muscular/metabolismo , Atrofia Muscular/patologia , Fator de Indução de Apoptose/metabolismo , Fibras Musculares de Contração Lenta/metabolismo , Fibras Musculares de Contração Rápida/metabolismo , Fibras Musculares de Contração Rápida/patologia , Endodesoxirribonucleases/metabolismo , Condicionamento Físico Animal/métodos , Condicionamento Físico Animal/fisiologia , Músculo Esquelético/metabolismo , Jejum Intermitente , Poli(ADP-Ribose) Polimerase-1RESUMO
PURPOSE OF REVIEW: The gut microbiome regulates several health and disease-related processes. However, the potential bidirectional relationship between the gut microbiome and physical exercise remains uncertain. Here, we review the evidence related to the gut microbiome in athletes. RECENT FINDINGS: The effect of physical exercise on the intestinal microbiome and intestinal epithelial cells depends on the type, volume, and intensity of the activity. Strenuous exercise negatively impacts the intestinal microbiome, but adequate training and dietary planning could mitigate these effects. An increase in short-chain fatty acids (SCFAs) concentrations can modulate signaling pathways in skeletal muscle, contributing to greater metabolic efficiency, preserving muscle glycogen, and consequently optimizing physical performance and recovery. Furthermore, higher SCFAs concentrations appear to lower inflammatory response, consequently preventing an exacerbated immune response and reducing the risk of infections among athletes. Regarding dietary interventions, the optimal diet composition for targeting the athlete's microbiome is not yet known. Likewise, the benefits or harms of using probiotics, synbiotics, and postbiotics are not well established, whereas prebiotics appear to optimize SCFAs production. SUMMARY: The intestinal microbiome plays an important role in modulating health, performance, and recovery in athletes. SCFAs appear to be the main intestinal metabolite related to these effects. Nutritional strategies focusing on the intestinal microbiome need to be developed and tested in well controlled clinical trials.
Assuntos
Atletas , Exercício Físico , Ácidos Graxos Voláteis , Microbioma Gastrointestinal , Humanos , Microbioma Gastrointestinal/fisiologia , Exercício Físico/fisiologia , Ácidos Graxos Voláteis/metabolismo , Probióticos/administração & dosagem , Prebióticos , Dieta/métodos , Músculo Esquelético/metabolismoRESUMO
Near-infrared spectroscopy combined with vascular occlusion test (NIRS-VOT) is a reactive hyperemia technique for in vivo evaluation of skeletal muscle microvascular reactivity. Previous studies using NIRS-VOT have been shown to be able to detect impairments in microvascular function in high-risk cardiovascular disease populations, such as older individuals. It has been demonstrated that older individuals have slower reactive hyperemia compared with young individuals. Importantly, older individuals also show less desaturation during ischemia compared with young individuals. Based on these findings, it has been suggested that the slower reactive hyperemia observed in older individuals is explained by the lower desaturation during blood flow occlusion (reduced ischemic stimulus). This retrospective analysis compared reactive hyperemia in 36 young and 47 older tissue desaturation-matched individuals that underwent 5-min blood flow occlusion. Overall, we showed that older individuals have impaired reactive hyperemia compared with young when matching for the degree of desaturation and blood flow occlusion time. These findings provide evidence that lower tissue desaturation during ischemia is not a major determinant of impaired reactive hyperemia in older individuals.NEW & NOTEWORTHY Previous findings have suggested that aging-related impairment in skeletal muscle reactive hyperemia is majorly influenced by a lower degree of tissue desaturation during ischemia in older individuals compared with young individuals. In a retrospective analysis including 83 tissue desaturation-matched individuals, we show that the degree of tissue desaturation is not a major determinant of aging-related impairments in reactive hyperemia.
Assuntos
Envelhecimento , Hiperemia , Microcirculação , Músculo Esquelético , Fluxo Sanguíneo Regional , Espectroscopia de Luz Próxima ao Infravermelho , Hiperemia/fisiopatologia , Músculo Esquelético/irrigação sanguínea , Músculo Esquelético/metabolismo , Músculo Esquelético/fisiopatologia , Humanos , Estudos Retrospectivos , Masculino , Envelhecimento/metabolismo , Envelhecimento/fisiologia , Idoso , Feminino , Adulto , Adulto Jovem , Pessoa de Meia-Idade , Fatores Etários , Isquemia/fisiopatologia , Isquemia/metabolismo , Oxigênio/sangue , Oxigênio/metabolismoRESUMO
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the dysfunction and death of motor neurons through multifactorial mechanisms that remain unclear. ALS has been recognized as a multisystemic disease, and the potential role of skeletal muscle in disease progression has been investigated. Reactive aldehydes formed as secondary lipid peroxidation products in the redox processes react with biomolecules, such as DNA, proteins, and amino acids, resulting in cytotoxic effects. 4-Hydroxy-2-nonenal (HNE) levels are elevated in the spinal cord motor neurons of ALS patients, and HNE-modified proteins have been identified in the spinal cord tissue of an ALS transgenic mice model, suggesting that reactive aldehydes can contribute to motor neuron degeneration in ALS. One biological pathway of aldehyde detoxification involves conjugation with glutathione (GSH) or carnosine (Car). Here, the detection and quantification of Car, GSH, GSSG (glutathione disulfide), and the corresponding adducts with HNE, Car-HNE, and GS-HNE, were performed in muscle and liver tissues of a hSOD1G93A ALS rat model by reverse-phase high-performance liquid chromatography coupled to electrospray ion trap tandem mass spectrometry in the selected reaction monitoring mode. A significant increase in the levels of GS-HNE and Car-HNE was observed in the muscle tissue of the end-stage ALS animals. Therefore, analyzing variations in the levels of these adducts in ALS animal tissue is crucial from a toxicological perspective and can contribute to the development of new therapeutic strategies.
Assuntos
Aldeídos , Esclerose Lateral Amiotrófica , Carnosina , Modelos Animais de Doenças , Glutationa , Animais , Esclerose Lateral Amiotrófica/metabolismo , Aldeídos/metabolismo , Aldeídos/química , Carnosina/metabolismo , Glutationa/metabolismo , Ratos , Músculo Esquelético/metabolismo , Humanos , Superóxido Dismutase/metabolismo , Masculino , Cromatografia Líquida de Alta Pressão , Ratos Transgênicos , Superóxido Dismutase-1/metabolismo , Ratos Sprague-DawleyRESUMO
The production and release of cortisol during stress responses are key regulators of growth in teleosts. Understanding the molecular responses to cortisol is crucial for the sustainable farming of rainbow trout (Oncorhynchus mykiss) and other salmonid species. While several studies have explored the genomic and non-genomic impacts of cortisol on fish growth and skeletal muscle development, the long-term effects driven by epigenetic mechanisms, such as cortisol-induced DNA methylation, remain unexplored. In this study, we analyzed the transcriptome and genome-wide DNA methylation in the skeletal muscle of rainbow trout seven days after cortisol administration. We identified 550 differentially expressed genes (DEGs) by RNA-seq and 9059 differentially methylated genes (DMGs) via whole-genome bisulfite sequencing (WGBS) analysis. KEGG enrichment analysis showed that cortisol modulates the differential expression of genes associated with nucleotide metabolism, ECM-receptor interaction, and the regulation of actin cytoskeleton pathways. Similarly, cortisol induced the differential methylation of genes associated with focal adhesion, adrenergic signaling in cardiomyocytes, and Wnt signaling. Through integrative analyses, we determined that 126 genes showed a negative correlation between up-regulated expression and down-regulated methylation. KEGG enrichment analysis of these genes indicated participation in ECM-receptor interaction, regulation of actin cytoskeleton, and focal adhesion. Using RT-qPCR, we confirmed the differential expression of lamb3, itga6, limk2, itgb4, capn2, and thbs1. This study revealed for the first time the molecular responses of skeletal muscle to cortisol at the transcriptomic and whole-genome DNA methylation levels in rainbow trout.
Assuntos
Metilação de DNA , Hidrocortisona , Músculo Esquelético , Oncorhynchus mykiss , Estresse Fisiológico , Transcriptoma , Animais , Oncorhynchus mykiss/genética , Oncorhynchus mykiss/metabolismo , Hidrocortisona/metabolismo , Hidrocortisona/farmacologia , Músculo Esquelético/metabolismo , Músculo Esquelético/efeitos dos fármacos , Estresse Fisiológico/genética , Epigênese Genética , Epigenômica/métodos , Perfilação da Expressão Gênica , Proteínas de Peixes/genética , Proteínas de Peixes/metabolismoRESUMO
The state of Maternal Protein Malnutrition (MPM) is associated with several deleterious effects, including inflammatory processes and dysregulation in oxidative balance, which can promote neurodegeneration. On the other hand, it is known that aerobic exercise can promote systemic health benefits, combating numerous chronic diseases. Therefore, we evaluate the effect of aerobic exercise training (AET) on indicators of mitochondrial bioenergetics, oxidative balance, endoplasmic reticulum stress, and neurotrophic factor in the prefrontal cortex of malnourished juvenile Wistar rats. Pregnant Wistar rats were fed with a diet containing 17% or 8% casein during pregnancy and lactation. At 30 days of life, male offspring were divided into 4 groups: Low-Protein Control (LS), Low-Protein Trained (LT), Normoprotein Control (NS), and Normoprotein Trained (NT). The trained groups performed an AET for 4 weeks, 5 days a week, 1 h a day per session. At 60 days of life, the animals were sacrificed and the skeletal muscle, and prefrontal cortex (PFC) were removed to evaluate the oxidative metabolism markers and gene expression of ATF-6, GRP78, PERK and BDNF. Our results showed that MPM impairs oxidative metabolism associated with higher oxidative and reticulum stress. However, AET restored the levels of indicators of mitochondrial bioenergetics, in addition to promoting resilience to cellular stress. AET at moderate intensity for 4 weeks in young Wistar rats can act as a non-pharmacological intervention in fighting against the deleterious effects of a protein-restricted maternal diet.
Assuntos
Fator Neurotrófico Derivado do Encéfalo , Mitocôndrias , Estresse Oxidativo , Condicionamento Físico Animal , Ratos Wistar , Animais , Feminino , Ratos , Mitocôndrias/metabolismo , Gravidez , Masculino , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Estresse do Retículo Endoplasmático , Biomarcadores/metabolismo , Córtex Pré-Frontal/metabolismo , Músculo Esquelético/metabolismo , Desnutrição/metabolismo , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Fator 6 Ativador da Transcrição/metabolismoRESUMO
The study aimed to evaluate the effects of Pereskia aculeata Miller (ora-pro-nobis [OPN]) flour on body and biochemical parameters, thermogenic activity, and molecular expression of markers in the muscle tissue of mice subjected to resistance training (RT). Twelve mice were randomly assigned to two groups (n=6 animals/group): G1: control (Control) fed a standard diet + RT and G2: experimental (OPN) fed a diet based on OPN flour + RT. The RT consisted of a 6-week program using a vertical ladder combined with a fixed weight attached to the animal. Several parameters were measured, including assessment of body composition, biochemical markers, thermogenic activity, and molecular (mRNA expression of interleukin (IL)-6, fibronectin type III domain-containing protein 5 (FNDC5), peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), nuclear respiratory factor 1 (NRF1), and mitochondrial transcription factor A (TFAM). The OPN group exhibited a decrease in body weight and visceral adiposity, higher energy expenditure, and lipid oxidation rate. In addition, it was observed an increase in muscle volume and in mRNA expression levels of IL-6, FNDC5, PGC-1α, and TFAM. These findings suggest that OPN flour could be a nutritional option to enhance performance in RT.
Assuntos
Farinha , Interleucina-6 , Músculo Esquelético , Miocinas , Treinamento Resistido , Animais , Humanos , Masculino , Camundongos , Composição Corporal/efeitos dos fármacos , Metabolismo Energético , Fibronectinas/metabolismo , Fibronectinas/genética , Interleucina-6/genética , Interleucina-6/metabolismo , Músculo Esquelético/metabolismo , Miocinas/genética , Miocinas/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , Condicionamento Físico Animal , Termogênese/efeitos dos fármacosRESUMO
AIM: The present study aimed to investigate the effects of a single bout of resistance exercise on mitophagy in human skeletal muscle (SkM). METHODS: Eight healthy men were recruited to complete an acute bout of one-leg resistance exercise. SkM biopsies were obtained one hour after exercise in the resting leg (Rest-leg) and the contracting leg (Ex-leg). Mitophagy was assessed using protein-related abundance, transmission electron microscopy (TEM), and fluorescence microscopy. RESULTS: Our results show that acute resistance exercise increased pro-fission protein phosphorylation (DRP1Ser616) and decreased mitophagy markers such as PARKIN and BNIP3L/NIX protein abundance in the Ex-leg. Additionally, mitochondrial complex IV decreased in the Ex-leg when compared to the Rest-leg. In the Ex-leg, TEM and immunofluorescence images showed mitochondrial cristae abnormalities, a mitochondrial fission phenotype, and increased mitophagosome-like structures in both subsarcolemmal and intermyofibrillar mitochondria. We also observed increased mitophagosome-like structures on the subsarcolemmal cleft and mitochondria in the extracellular space of SkM in the Ex-leg. We stimulated human primary myotubes with CCCP, which mimics mitophagy induction in the Ex-leg, and found that BNIP3L/NIX protein abundance decreased independently of lysosomal degradation. Finally, in another human cohort, we found a negative association between BNIP3L/NIX protein abundance with both mitophagosome-like structures and mitochondrial cristae density in the SkM. CONCLUSION: The findings suggest that a single bout of resistance exercise can initiate mitophagy, potentially involving mitochondrial ejection, in human skeletal muscle. BNIP3L/NIX is proposed as a sensitive marker for assessing mitophagy flux in SkM.
Assuntos
Mitofagia , Músculo Esquelético , Humanos , Mitofagia/fisiologia , Masculino , Músculo Esquelético/metabolismo , Músculo Esquelético/fisiologia , Adulto , Mitocôndrias Musculares/metabolismo , Mitocôndrias Musculares/ultraestrutura , Treinamento Resistido , Adulto Jovem , Proteínas de Membrana/metabolismoRESUMO
Although unfolded protein response (UPR) is essential for cellular protection, its prolonged activation may induce apoptosis, compromising cellular longevity. The aging process increases the endoplasmic reticulum (ER) stress in skeletal muscle. However, whether combined exercise can prevent age-induced ER stress in skeletal muscle remains unknown. Evidence suggests that ER stress may increase inflammation by counteracting the positive effects of interleukin-10 (IL-10), whereas its administration in cells inhibits ER stress and apoptosis. This study verified the effects of aging and combined exercise on physical performance, ER stress markers, and inflammation in the quadriceps of mice. Moreover, we verified the effects of IL-10 on ER stress markers. C57BL/6 mice were distributed into young (Y, 6 mo old), old sedentary (OS, sedentary, 24 mo old), and old trained group (OT, submitted to short-term combined exercise, 24 mo old). To clarify the role of IL-10 in UPR pathways, knockout mice lacking IL-10 were used. The OS mice presented worse physical performance and higher ER stress-related proteins, such as C/EBP homologous protein (CHOP) and phospho-eukaryotic translation initiation factor 2 alpha (p-eIF2α/eIF2α). The exercise protocol increased muscle strength and IL-10 protein levels in OT while inducing the downregulation of CHOP protein levels compared with OS. Furthermore, mice lacking IL-10 increased BiP, CHOP, and p-eIF2α/eIF2α protein levels, indicating this cytokine can regulate the ER stress response in skeletal muscle. Bioinformatics analysis showed that endurance and resistance training downregulated DNA damage inducible transcript 3 (DDIT3) and XBP1 gene expression in the vastus lateralis of older people, reinforcing our findings. Thus, combined exercise is a potential therapeutic intervention for promoting adjustments in ER stress markers in aged skeletal muscle.NEW & NOTEWORTHY Aging elevates endoplasmic reticulum (ER) stress in skeletal muscle, potentially heightening inflammation by opposing interleukin-10 (IL-10) effects. This study found that short-term combined exercise boosted strength and IL-10 protein levels while reducing CHOP protein levels in older mice. In addition, IL-10-deficient mice exhibited increased ER stress markers, highlighting IL-10's role in regulating ER stress in skeletal muscle. Consequently, combined exercise emerges as a therapeutic intervention to elevate IL-10 and adjust ER stress markers in aging.