Search Results (58)

Hypoxia represents a critical environmental stressor in aquaculture, significantly disrupting aquatic organisms’ physiological homeostasis and thereby constraining the sustainable development of aquaculture industries. To elucidate the mechanisms underlying hypoxia-induced metabolic regulation in aquatic species, this study employed hybrid yellow catfish (Pelteobagrus vachelli ♀ × Leiocassis longirostris ♂) as a model organism to systematically investigate the multidimensional physiological responses in brain, liver, and muscle tissues under hypoxia (0.7 mg/L) and reoxygenation (7.0 mg/L) conditions. Through qRT-PCR and enzymatic activity analyses, we comprehensively assessed molecular alterations associated with oxygen sensing (HIF-1α gene), respiratory metabolism (PFKL, HK1, PK, CS, and LDHA genes and corresponding enzyme activities), oxidative stress (SOD1, SOD2, GSH-PX, and CAT genes, along with LPO, MDA, PCO, T-SOD, GSH-PX, and CAT levels), apoptosis (Caspase-3, Bax/Bcl-2), inflammatory response (IL-1β, IKKβ), and mitochondrial function (COXIV, PGC-1α, ATP5A1). Key findings demonstrated pronounced HIF-1α activation across all examined tissues. Hepatic tissues exhibited adaptive metabolic reprogramming from aerobic to anaerobic metabolism, whereas cerebral tissues displayed suppressed anaerobic glycolysis during prolonged hypoxia, and muscular tissues manifested concurrent inhibition of both glycolytic and aerobic metabolic pathways. Notably, skeletal muscle exhibited marked oxidative stress accompanied by mitochondrial dysfunction, exacerbated inflammation, and apoptosis activation during hypoxia/reoxygenation cycles. This study delineates tissue-specific adaptive mechanisms to hypoxia in yellow catfish, providing theoretical foundations for both piscine hypoxia physiology research and aquaculture practices. Full article

Background: Aerobic exercise induces a range of complex molecular adaptations in skeletal muscle. However, a complete understanding of the specific transcriptional changes following exercise warrants further research. Methods: This study aimed to identify gene expression patterns following acute aerobic exercise by analyzing Gene Expression Omnibus (GEO) datasets. We performed a comparative analysis of transcriptional profiles of related genes in two independent studies, focusing on both established and novel genes involved in muscle physiology. Results: Our analysis revealed ten consistently upregulated and eight downregulated genes across both datasets. The upregulated genes were predominantly associated with mitochondrial function and cellular respiration, including MDH1, ATP5MC1, ATP5IB, and ATP5F1A. Conversely, downregulated genes such as YTHDC1, CDK5RAP2, and PALS2 were implicated in vascular structure and cellular organization. Importantly, our findings also revealed novel exercise-responsive genes not previously characterized in this context. Among these, MRPL41 and VEGF were significantly upregulated and are associated with p53-mediated apoptotic signaling and fatty acid metabolism, respectively. Novel downregulated genes included LIMCH1, CMYA5, and FOXJ3, which are putatively involved in cytoskeletal dynamics and muscle fiber type specification. Conclusions: These findings enhance our understanding of the transcriptional landscape of skeletal muscle following acute aerobic exercise and identify novel molecular targets for further investigation in the fields of exercise physiology and metabolic health. Full article

Background: Sarcopenia is a syndrome associated with aging, characterized by a progressive decline in skeletal muscle mass and function. Its onset compromises the health and longevity of older adults by increasing susceptibility to falls, fractures, and various comorbid conditions, thereby diminishing quality of life and capacity for independent living. Accumulating evidence indicates that moderate-intensity aerobic exercise is an effective strategy for promoting overall health in older adults and exerts a beneficial effect that mitigates age-related sarcopenia. However, the underlying molecular mechanisms through which exercise confers these protective effects remain incompletely understood. Methods: In this study, we established a naturally aging mouse model to investigate the effects of a 16-week treadmill-based aerobic exercise regimen on skeletal muscle physiology. Results: Results showed that aerobic exercise mitigated age-related declines in muscle mass and function, enhanced markers associated with protein synthesis, reduced oxidative stress, and modulated the expression of genes and proteins implicated in mitochondrial quality control. Notably, a single session of aerobic exercise acutely elevated circulating levels of β-hydroxybutyrate (β-HB) and upregulated the expression of BDH1, HCAR2, and PPARG in the skeletal muscle, suggesting a possible role of β-HB–related signaling in exercise-induced muscle adaptations. However, although these findings support the beneficial effects of aerobic exercise on skeletal muscle aging, further investigation is warranted to elucidate the causal relationships and to characterize the chronic signaling mechanisms involved. Conclusions: This study offers preliminary insights into how aerobic exercise may modulate mitochondrial quality control and β-HB–associated signaling pathways during aging. Full article

Background: Physical activity induces a range of physiological and molecular adaptations, particularly affecting skeletal muscle and the cardiovascular system, regulating both tissue architecture and metabolic pathways. Emerging evidence suggests that PIWI-interacting RNAs (piRNAs) may serve as potential biomarkers for these adaptations. Here, we analyzed piRNA patterns in the context of exercise. Methods: This study selected eight participants of the iReAct study (DRKS00017446) for piRNA analysis. Baseline assessments included demographic profiling and fitness evaluation, particularly maximal oxygen uptake (V̇O2max) assessment. In addition, blood samples were collected pre- and (for six of the eight participants) post- standard reference training sessions. Subsequently, subjects underwent 6-week training protocols, employing standardized high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) regimens. Next, RNA sequencing was conducted to identify differentially expressed piRNAs, and correlation analyses were performed between piRNA expression patterns and training-associated changes in V̇O2max. Finally, to identify piRNAs potentially of interest in the context of exercise, different screening procedures were applied. Results: There were unique and specific changes in individual piRNA expression levels in response to exercise. In addition, we could define correlations of piRNA expression patterns, namely of piR-32886, piR-33151, piR-12547, and piR-33074, with changes in V̇O2max. These correlations did not reach significance in the small sample size of this pilot study, but might be verified in larger, confirming studies. Conclusions: This hypothesis-generating study identifies characteristic piRNA patterns in the context of exercise. Their significance as biomarkers is yet to be determined. Full article

Skeletal muscle health and function are closely linked to long-term aerobic exercise, particularly in enhancing muscle metabolism and regulating gene expression. Regular endurance training can significantly ameliorate metabolic dysfunction and prevent chronic diseases. However, the precise molecular mechanisms underlying skeletal muscle adaptations to long-term aerobic exercise require further clarification. To address this, we integrated transcriptomic and single-cell omics datasets from multiple long-term aerobic exercise models retrieved from the GEO database. After merging and batch correction, differential expression analysis identified 204 DEGs, including 110 upregulated and 94 downregulated genes. Key feature genes were screened using Lasso regression, SVM-RFE, and Random Forest machine learning algorithms, validated by RT-qPCR, and refined through PPI network analysis. Among them, Fos and Tnfrsf12a were significantly downregulated following long-term aerobic exercise. Notably, Fos exhibited a more pronounced decrease than Tnfrsf12a, and was strongly associated with inflammation and muscle regeneration. PPI network analysis indicated that Fos interacted with genes such as Casp3, Egr1, Aft3, Hspa5, Src, and Igf2. GO, KEGG, and GSEA enrichment analyses revealed that Fos is involved in skeletal muscle differentiation, tissue remodeling, and the NF-κB inflammatory pathway. ssGSEA analysis further showed that samples with low Fos expression had significantly elevated Th1/Th2 and Treg cell infiltration. Single-cell analysis confirmed preferential Fos expression in muscle fiber/adipocyte progenitors, satellite cells, and tenocytes, all critical for myogenesis. In summary, our findings suggest that long-term aerobic exercise downregulates Fos, potentially alleviating inflammation and enhancing satellite cell-mediated muscle regeneration. Fos may serve as a central regulator of skeletal muscle remodeling during long-term aerobic exercise. Full article

Muscle fibers, as the fundamental units of muscle tissue, play a crucial role in determining skeletal muscle function through their growth, development, and composition. To investigate changes in muscle fiber types and their regulatory mechanisms in Mongolian horses (MG), Xilingol horses (XL), and Grassland-Thoroughbreds (CY), we conducted histological and bioinformatic analyses on the gluteus medius muscle of these three horse breeds. Immunofluorescence analysis revealed that Grassland-Thoroughbreds had the highest proportion of fast-twitch muscle fibers at 78.63%, while Mongolian horses had the lowest proportion at 57.54%. Whole-transcriptome analysis identified 105 differentially expressed genes (DEGs) in the CY vs. MG comparison and 104 DEGs in the CY vs. XL comparison. Time-series expression profiling grouped the DEGs into eight gene sets, with three sets showing significantly up-regulated or down-regulated expression patterns (p < 0.05). Additionally, 280 differentially expressed long non-coding RNAs (DELs) were identified in CY vs. MG, and 213 DELs were identified in CY vs. XL. A total of 32 differentially expressed microRNAs (DEMIRs) were identified in CY vs. MG, while 44 DEMIRs were found in CY vs. XL. Functional enrichment analysis indicated that the DEGs were significantly enriched in essential biological processes, such as actin filament organization, muscle contraction, and protein phosphorylation. KEGG pathway analysis showed their involvement in key signaling pathways, including the mTOR signaling pathway, FoxO signaling pathway, and HIF-1 signaling pathway. Furthermore, functional variation-based analyses revealed associations between non-coding RNAs and mRNAs, with some non-coding RNAs targeting genes potentially related to muscle function regulation. These findings provide valuable insights into the molecular basis for the environmental adaptability, athletic performance, and muscle characteristics in horses, offering new perspectives for the breeding of Grassland-Thoroughbreds. Full article

Background/Objectives: Sarcopenia, characterized by the progressive loss of muscle mass and strength, is linked to physical disability, metabolic dysfunction, and an increased risk of mortality. Exercise therapy is currently acknowledged as a viable approach for addressing sarcopenia. Nevertheless, the molecular mechanisms behind exercise training or physical activity remain poorly understood. The disruption of mitochondrial homeostasis is implicated in the pathogenesis of sarcopenia. Exercise training effectively delays the onset of sarcopenia by significantly maintaining mitochondrial homeostasis, including promoting mitophagy, improving mitochondrial biogenesis, balancing mitochondrial dynamics, and maintaining mitochondrial redox. Exerkines (e.g., adipokines, myokines, hepatokines, and osteokines), signaling molecules released in response to exercise training, may potentially contribute to skeletal muscle metabolism through ameliorating mitochondrial homeostasis, reducing inflammation, and regulating protein synthesis as a defense against sarcopenia. Methods: In this review, we provide a detailed summary of exercise-induced exerkines and confer their benefit, with particular focus on their impact on mitochondrial homeostasis in the context of sarcopenia. Results: Exercise induces substantial adaptations in skeletal muscle, including increased muscle mass, improved muscle regeneration and hypertrophy, elevated hormone release, and enhanced mitochondrial function. An expanding body of research highlights that exerkines have the potential to regulate processes such as mitophagy, mitochondrial biogenesis, dynamics, autophagy, and redox balance. These mechanisms contribute to the maintenance of mitochondrial homeostasis, thereby supporting skeletal muscle metabolism and mitochondrial health. Conclusions: Through a comprehensive investigation of the molecular mechanisms within mitochondria, the context reveals new insights into the potential of exerkines as key exercise-protective sensors for combating sarcopenia. Full article

Background/Objectives: Early weaning management followed by energy supplementation can lead to metabolic alterations in the calf that exert long-term effects on the animal’s health and performance. It is believed that the main molecular basis underlying these metabolic adaptations are epigenetic mechanisms that regulate, activate, or silence genes at different stages of development and/or in response to different environmental stimuli. However, little is known about postnatal metabolic programming in Bos indicus. Therefore, this study aimed to compare the DNA methylation profile of Nellore animals submitted to conventional and early weaning and to correlate the findings with genes differentially expressed in the Longissimus thoracis skeletal muscle of Bos indicus cattle. Methods: For this, we used Reduced Representation Bisulfite Sequencing (RRBS) and RNA-Sequencing techniques to prospect differentially methylated genes (DMGs). Results: A total of 481 differentially methylated regions were identified, with 52% (250) being hypermethylated and 48% (231) hypomethylated. Functional enrichment analysis of 53 differentially methylated and differentially expressed genes was performed. The main enriched terms and pathways were associated with 3′-5′-cyclic adenosine monophosphate (cAMP) signaling, which presents the upregulated adenylate cyclase 3 (ADCY3) gene and significatively hypomethylated in the promoter region. Alterations in cAMP signaling are involved in numerous processes, many of them related to lipid metabolism. The relative differential expression of key genes of this pathway demonstrates the relationship between cAMP signaling and de novo lipogenesis. Conclusions: These findings suggest an important role of postnatal metabolic programming through DNA methylation mechanisms in determining fat deposition in beef. Full article

Photobiomodulation (PBM) has been applied in biomedical technology to improve cellular responses. Specifically in sports medicine, it is used to accelerate metabolic and structural repair and adaptation in skeletal muscle under stress overload. Currently, PBM has been associated with static Magnetic Field (sMF) in clinical applications, enhancing the effects displayed by PBM when used in isolation. However, the biochemical and molecular effects of PBM-sMF in myoblasts remain unknown. This study aimed to investigate the effects of PBM combined with static magnetic field (PBM-sMF) at different doses in C2C12 muscle cells in the presence or absence of hydrogen peroxide (H₂O₂), a standard oxidant. Different spectrophotometric and fluorometric assays were conducted after cellular treatments. PBM-sMF was shown to be effective compared to H₂O₂ regarding cell viability and release of nitric oxide (NO), dsDNA, and reactive oxygen species (ROS) levels. It positively modulated mitochondrial membrane potential (ΔΨm) and cytochrome c oxidase (COX) activity under normal conditions and restored both to normal levels when impacted by H₂O₂. Regarding apoptosis, the recovery in viable cells observed on PBM-sMF treated cells was dose-dependent. In conclusion, PBM-sMF has a biphasic effect in normal and oxidative environments and may differently modulate myoblast cells depending on their redox status. Full article

The skeletal muscles of teleost fish encompass heterogeneous muscle types, termed slow-twitch muscle (SM) and fast-twitch muscle (FM), characterized by distinct morphological, anatomical, histological, biochemical, and physiological attributes, driving different swimming behaviors. Despite the central role of metabolism in regulating skeletal muscle types and functions, comprehensive metabolomics investigations focusing on the metabolic differences between these muscle types are lacking. To reveal the differences in metabolic characteristics between the SM and FM of teleost, we conducted an untargeted metabolomics analysis using Pseudocaranx dentex as a representative model and identified 411 differential metabolites (DFMs), of which 345 exhibited higher contents in SM and 66 in FM. KEGG enrichment analysis showed that these DFMs were enriched in the metabolic processes of lipids, amino acids, carbohydrates, purines, and vitamins, suggesting that there were significant differences between the SM and FM in multiple metabolic pathways, especially in the metabolism of energy substances. Furthermore, an integrative analysis of metabolite contents, enzymatic activity assays, and gene expression levels involved in ATP-PCr phosphate, anaerobic glycolysis, and aerobic oxidative energy systems was performed to explore the potential regulatory mechanisms of energy metabolism differences. The results unveiled a set of differential metabolites, enzymes, and genes between the SM and FM, providing compelling molecular evidence of the FM achieving a higher anaerobic energy supply capacity through the ATP-PCr phosphate and glycolysis energy systems, while the SM obtains greater energy supply capacity via aerobic oxidation. These findings significantly advance our understanding of the metabolic profiles and related regulatory mechanisms of skeletal muscles, thereby expanding the knowledge of metabolic physiology and ecological adaptation in teleost fish. Full article

Jeryak is the F1 generation of the cross between Gannan yak and Jersey cattle, which has the advantages of fast growth and high adaptability. The growth and development of skeletal muscle is closely linked to meat production and the quality of meat. However, the molecular regulatory mechanisms of muscle growth differences between Gannan yak and Jeryak analyzed from the perspective of chromatin opening have not been reported. In this study, ATAC-seq was used to analyze the difference of chromatin openness in longissimus muscle of Gannan yak and Jeryak. It was found that chromatin accessibility was more enriched in Jeryak compared to Gannan yak, especially in the range of the transcription start site (TSS) ± 2 kb. GO and KEGG enrichment analysis indicate that differential peak-associated genes are involved in the negative regulation of muscle adaptation and the Hippo signaling pathway. Integration analysis of ATAC-seq and RNA-seq revealed overlapping genes were significantly enriched during skeletal muscle cell differentiation and muscle organ morphogenesis. At the same time, we screened FOXO1, ZBED6, CRY2 and CFL2 for possible involvement in skeletal muscle development, constructed a genes and transcription factors network map, and found that some transcription factors (TFs), including YY1, KLF4, KLF5 and Bach1, were involved in skeletal muscle development. Overall, we have gained a comprehensive understanding of the key factors that impact skeletal muscle development in various breeds of cattle, providing new insights for future analysis of the molecular regulatory mechanisms involved in muscle growth and development. Full article

Gene therapy approaches may target skeletal muscle due to its high protein-expressing nature and vascularization. Intramuscular plasmid DNA (pDNA) delivery via pulsed electric fields (PEFs) can be termed electroporation or electrotransfer. Nonviral delivery of plasmids to cells and tissues activates DNA-sensing pathways. The central signaling complex in cytosolic DNA sensing is the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING). The effects of pDNA electrotransfer on the signaling of STING, a key adapter protein, remain incompletely characterized. STING undergoes several post-translational modifications which modulate its function, including palmitoylation. This study demonstrated that in mouse skeletal muscle, STING was constitutively palmitoylated at two sites, while an additional site was modified following electroporation independent of the presence of pDNA. This third palmitoylation site correlated with STING polymerization but not with STING activation. Expression of several palmitoyl acyltransferases, including zinc finger and DHHC motif containing 1 (zDHHC1), coincided with STING activation. Expression of several depalmitoylases, including palmitoyl protein thioesterase 2 (PPT2), was diminished in all PEF application groups. Therefore, STING may not be regulated by active modification by palmitate after electroporation but inversely by the downregulation of palmitate removal. These findings unveil intricate molecular changes induced by PEF application. Full article

A better understanding of the cellular and molecular mechanisms that are involved in skeletal muscle adaptation to exercise is fundamentally important to take full advantage of the enormous benefits that exercise training offers in disease prevention and therapy. The aim of this study was to elucidate the transcriptional signatures that distinguish the endurance-trained and untrained muscles in young adult males (24 ± 3.5 years). We characterized baseline differences as well as acute exercise-induced transcriptome responses in vastus lateralis biopsy specimens of endurance-trained athletes (ET; n = 8; VO₂max, 67.2 ± 8.9 mL/min/kg) and sedentary healthy volunteers (SED; n = 8; VO₂max, 40.3 ± 7.6 mL/min/kg) using microarray technology. A second cohort of SED volunteers (SED-T; n = 10) followed an 8-week endurance training program to assess expression changes of selected marker genes in the course of skeletal muscle adaptation. We deciphered differential baseline signatures that reflected major differences in the oxidative and metabolic capacity of the endurance-trained and untrained muscles. SED-T individuals in the training group displayed an up-regulation of nodal regulators of oxidative adaptation after 3 weeks of training and a significant shift toward the ET signature after 8 weeks. Transcriptome changes provoked by 1 h of intense cycling exercise only poorly overlapped with the genes that constituted the differential baseline signature of ETs and SEDs. Overall, acute exercise-induced transcriptional responses were connected to pathways of contractile, oxidative, and inflammatory stress and revealed a complex and highly regulated framework of interwoven signaling cascades to cope with exercise-provoked homeostatic challenges. While temporal transcriptional programs that were activated in SEDs and ETs were quite similar, the quantitative divergence in the acute response transcriptomes implicated divergent kinetics of gene induction and repression following an acute bout of exercise. Together, our results provide an extensive examination of the transcriptional framework that underlies skeletal muscle plasticity. Full article

Mounting evidence underscores the intricate interplay between the immune system and skeletal muscles in Duchenne muscular dystrophy (DMD), as well as during regular muscle regeneration. While immune cell infiltration into skeletal muscles stands out as a prominent feature in the disease pathophysiology, a myriad of secondary defects involving metabolic and inflammatory pathways persist, with the key players yet to be fully elucidated. Steroids, currently the sole effective therapy for delaying onset and symptom control, come with adverse side effects, limiting their widespread use. Preliminary evidence spotlighting the distinctive features of T cell profiling in DMD prompts the immuno-characterization of circulating cells. A molecular analysis of their transcriptome and secretome holds the promise of identifying a subpopulation of cells suitable as disease biomarkers. Furthermore, it provides a gateway to unraveling new pathological pathways and pinpointing potential therapeutic targets. Simultaneously, the last decade has witnessed the emergence of novel approaches. The development and equilibrium of both innate and adaptive immune systems are intricately linked to the gut microbiota. Modulating microbiota-derived metabolites could potentially exacerbate muscle damage through immune system activation. Concurrently, genome sequencing has conferred clinical utility for rare disease diagnosis since innovative methodologies have been deployed to interpret the functional consequences of genomic variations. Despite numerous genes falling short as clinical targets for MD, the exploration of Tdark genes holds promise for unearthing novel and uncharted therapeutic insights. In the quest to expedite the translation of fundamental knowledge into clinical applications, the identification of novel biomarkers and disease targets is paramount. This initiative not only advances our understanding but also paves the way for the design of innovative therapeutic strategies, contributing to enhanced care for individuals grappling with these incapacitating diseases. Full article

Fetuses with intrauterine growth restriction (FGR) have impaired oxidative and energy metabolism, with persistent consequences on their postnatal development. In this study, we test the hypothesis that FGR skeletal muscle has lower mitochondrial respiration rate and alters the transcriptomic profiles associated with energy metabolism in an ovine model. At late gestation, mitochondrial oxygen consumption rates (OCRs) and transcriptome profiles were evaluated in the skeletal muscle collected from FGR and control fetuses. The ex vivo mitochondrial OCRs were reduced (p < 0.01) in permeabilized FGR soleus muscle compared to the control muscle but only with pyruvate as the metabolic substrate. Mitochondrial OCRs were similar between the FGR and control groups for palmitoyl-carnitine (fatty acid-driven) or pyruvate plus palmitoyl-carnitine metabolic substrates. A total of 2284 genes were differentially expressed in the semitendinosus muscle from growth restricted fetuses (false discovery rate (FDR) ≤ 0.05). A pathway analysis showed that the upregulated genes (FGR compared to control) were overrepresented for autophagy, HIF-1, AMPK, and FOXO signaling pathways (all with an FDR < 0.05). In addition, the expression of genes modulating pyruvate’s entry into the TCA cycle was downregulated, whereas the genes encoding key fatty acid oxidation enzymes were upregulated in the FGR muscle. These findings show that FGR skeletal muscle had attenuated mitochondrial pyruvate oxidation, possibly associated with the inability of pyruvate to enter into the TCA cycle, and that fatty acid oxidation might compensate for the attenuated energy metabolism. The current study provided phenotypic and molecular evidence for adaptive deficiencies in FGR skeletal muscle. Full article