Impact of Aerobic Training on Transcriptomic Changes in Skeletal Muscle of Rats with Cardiac Cachexia
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PROVIDER: PRJNA1271088 | ENA |
REPOSITORIES: ENA
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Project description:Cardiac cachexia (CC) is an advanced stage of heart failure (HF) characterized by structural and functional abnormalities in skeletal muscle, leading to muscle loss. Aerobic training provides benefits; however, the underlying molecular mechanisms remain poorly understood. This study aimed to investigate the therapeutic effects of aerobic training on transcriptomic alterations associated with disease progression in cachectic skeletal muscle. HF was induced in male Wistar rats by a single monocrotaline injection (60mg/Kg). Aerobic training consisted of treadmill running for 30min at ~55% of maximal capacity, 5x/week for 4 weeks. Assessments included body mass, right ventricle mass, skeletal muscle fiber size and exercise tolerance. RNA sequencing analysis was per-formed on the medial gastrocnemius muscle. Sedentary cachectic rats exhibited 114 differentially expressed genes (DEGs) while exercised cachectic rats had only 18 DEGs compared to their respective controls. GO enrichment, pathway enrichment, and weighted gene co-expression network analysis (WGCNA) identified key DEGs as po-tential hub genes involved in disrupted lipid metabolism and muscle remodeling in sedentary CC rats, which were not observed in the exercised CC rats. These findings suggest that aerobic training mitigates transcriptional alterations related to lipid me-tabolism and muscle remodeling in rats with CC, highlighting its therapeutic potential.
2025-07-16 | GSE298775 | GEO
Project description:Microarray analysis was performed with RNA isolated from vastus lateralis muscle biopsies of lean/overweight subjects following 18 days of aerobic exercise training. Samples from lean active individuals were also included. Exercise training led to robust changes in trained muscle. The lean active group profile was distinct from the pre-exercise samples. These results help define the molecular changes associated with aerobic training and contrast with an active phenotype.
2020-05-01 | GSE139258 | GEO
Project description:The mechanisms underlying exercise-induced effects in the skeletal muscle during cancer cachexia progression have not been fully described. Here, we tested the hypothesis that different exercise training protocols could attenuate metabolic impairment in a severe model of cancer cachexia. Moderate-intensity training (MIT) and high-intensity interval training (HIIT) improved running capacity and prolonged lifespan in tumor-bearing rats. HIIT also reduced oxidative stress and reestablished muscle contractile function. An unbiased proteomics screening revealed that COP9 signalosome complex subunit 2 (COPS2), also known as thyroid receptor interacting protein 15 (TRIP15) or ALIEN, is one of the most downregulated proteins at the early stage of cancer cachexia progression. HIIT restored COPS2/TRIP15/ALIEN protein expression to the control levels. Moreover, lung cancer patients with low endurance capacity had lower muscle COPS2/TRIP15/ALIEN protein content compared to age- and sex-matched control subjects. We further established an in vitro model of cancer-induced muscle wasting using tumor cells-conditioned media to explore the potential protective role of COPS2/TRIP15/ALIEN for myotubes homeostasis. This in vitro model indicate that tumor cells produce factors that directly affect myotube metabolism, but COPS2/TRIP15/ALIEN overexpression is not able to fully reestablish metabolic homeostasis and protein content in myotubes incubated with tumor cells-conditioned media. The current study provides new insight into the role of exercise training as a co-therapy for cancer cachexia and uncovers COPS2/TRIP15/ALIEN as a novel potential target for cancer cachexia.
2021-09-08 | PXD013226 | Pride
Project description:The processes of adaptation to environmental heat and aerobic exercise training improve efficiency in various body systems and bring about acclimatory homeostasis. In order to examine the global genomic responses of the soleus and heart following exposure of rats to these stressors, nylon cDNA Atlas Array was used. Male rats were exposed to one of the following stressors: heat acclimation, aerobic training (treadmill), and combined heat acclimation and aerobic training for short (2, 3 days) and long (1 mo) time period. The study comprised seven experimental groups: Controls-untreated. Heat acclimated groups (2dac, Acc)– exposure to environmental heat at 34C for 2 or 30 days. Exercise groups (3dex, Ex)– graduated training protocol under normothermic conditions for 3 and 30 days at 24C. Exercise training and heat acclimation – (3dexac, ExAc)- exposed to both environmental heat and aerobic exercise as above. The Series data tables appended below: 1) Heart - normalized log2 ratio of geomeans defined as treatment/control 2) Soleus - normalized log2 ratio of geomeans defined as treatment/control Keywords: stress response
2007-12-31 | GSE7799 | GEO
Project description:The processes of adaptation to environmental heat and aerobic exercise training improve efficiency in various body systems and bring about acclimatory homeostasis. In order to examine the global genomic responses of the soleus and heart following exposure of rats to these stressors, nylon cDNA Atlas Array was used. Male rats were exposed to one of the following stressors: heat acclimation, aerobic training (treadmill), and combined heat acclimation and aerobic training for short (2, 3 days) and long (1 mo) time period. The study comprised seven experimental groups: Controls-untreated. Heat acclimated groups (2dac, Acc)â exposure to environmental heat at 34C for 2 or 30 days. Exercise groups (3dex, Ex)â graduated training protocol under normothermic conditions for 3 and 30 days at 24C. Exercise training and heat acclimation â (3dexac, ExAc)- exposed to both environmental heat and aerobic exercise as above. The Series data tables appended below: 1) Heart - normalized log2 ratio of geomeans defined as treatment/control 2) Soleus - normalized log2 ratio of geomeans defined as treatment/control 21 samples, 3 pool each, of: 1)Â Control untreated rats 2)Â Long-term heat acclimated rats 3)Â Long-term aerobic-exercised trained rats. 4)Â Rats exposed to long-term heat acclimation and exercise training. 5)Â Short term heat acclimated rats. 6)Â Short term aerobic exercised trained rats 7)Â Rats exposed to short-term heat acclimation and exercise training.
2010-05-27 | E-GEOD-7799 | biostudies-arrayexpress
Project description:The molecular pathways which are activated and contribute to physiological remodeling of skeletal muscle in response to endurance exercise have not been fully characterized. We previously reported that ~800 gene transcripts are regulated following 6 weeks of supervised endurance training in young sedentary males, referred to as the training responsive transcriptome (TRT). Here we utilized this database together with data on biological variation in muscle adaptation to aerobic endurance training in both humans and a novel out-bred rodent model to study the potential regulatory molecules that coordinate this complex network of genes. We identified three DNA sequences representing RUNX1, SOX9, and PAX3 transcription factor binding sites as over-represented in the TRT. In turn, miRNA profiling indicated that several miRNAs targeting RUNX1, SOX9 and PAX3 were down-regulated by endurance training. The TRT was then examined by contrasting subjects who demonstrated the least vs. the greatest improvement in aerobic capacity (low vs. high responders), and at least 100 of the 800 TRT genes were differentially regulated, thus suggesting regulation of these genes may be important for improving aerobic capacity. In high responders, pro-angiogenic and tissue developmental networks emerged as key candidates for coordinating tissue aerobic adaptation. Beyond RNA level validation there were several DNA variants that associated with VO(2)max trainability in the HERITAGE Family Study but these did not pass conservative Bonferroni adjustment. In addition, in a rat model selected across 10 generations for high aerobic training responsiveness, we found that both the TRT and a homologous subset of the human high responder genes were regulated to a greater degree in high responder rodent skeletal muscle. This analysis provides a comprehensive map of the transcriptomic features important for aerobic exercise-induced improvements in maximal oxygen consumption. This data is from skeletal muscle post 6 weeks of endurance exercise training.
2012-02-10 | E-GEOD-35659 | biostudies-arrayexpress
Project description:The molecular pathways which are activated and contribute to physiological remodeling of skeletal muscle in response to endurance exercise have not been fully characterized. We previously reported that ~800 gene transcripts are regulated following 6 weeks of supervised endurance training in young sedentary males, referred to as the training responsive transcriptome (TRT). Here we utilized this database together with data on biological variation in muscle adaptation to aerobic endurance training in both humans and a novel out-bred rodent model to study the potential regulatory molecules that coordinate this complex network of genes. We identified three DNA sequences representing RUNX1, SOX9, and PAX3 transcription factor binding sites as over-represented in the TRT. In turn, miRNA profiling indicated that several miRNAs targeting RUNX1, SOX9 and PAX3 were down-regulated by endurance training. The TRT was then examined by contrasting subjects who demonstrated the least vs. the greatest improvement in aerobic capacity (low vs. high responders), and at least 100 of the 800 TRT genes were differentially regulated, thus suggesting regulation of these genes may be important for improving aerobic capacity. In high responders, pro-angiogenic and tissue developmental networks emerged as key candidates for coordinating tissue aerobic adaptation. Beyond RNA level validation there were several DNA variants that associated with VO(2)max trainability in the HERITAGE Family Study but these did not pass conservative Bonferroni adjustment. In addition, in a rat model selected across 10 generations for high aerobic training responsiveness, we found that both the TRT and a homologous subset of the human high responder genes were regulated to a greater degree in high responder rodent skeletal muscle. This analysis provides a comprehensive map of the transcriptomic features important for aerobic exercise-induced improvements in maximal oxygen consumption.
2012-02-10 | GSE35659 | GEO
Project description:Low aerobic exercise capacity is a risk factor for diabetes and strong predictor of mortality; yet some individuals are exercise resistant, and unable to improve exercise capacity through exercise training. To test the hypothesis that resistance to aerobic exercise training underlies metabolic disease-risk, we used selective breeding for 15 generation to develop rat models of low- and high-aerobic response to training. Before exercise training, rats selected as low- and high-responders had similar exercise capacities. However, after 8-wks of treadmill training low-responders failed to improve their exercise capacity, while high-responders improved by 54%. Remarkably, low-responders to aerobic training exhibited pronounced metabolic dysfunction characterized by insulin resistance and increased adiposity, demonstrating that the exercise resistant phenotype segregates with disease risk. Low-responders had impaired exercise-induced angiogenes0is in muscle; however, mitochondrial capacity was intact and increased normally with exercise training, demonstrating that mitochondria are not limiting for aerobic adaptation or responsible for metabolic dysfunction in low-responders. Low-responders had increased stress/inflammatory signaling and altered TGFβ signaling, characterized by hyperphosphorylation of a novel exercise-regulated phosphorylation site on SMAD2. Using this powerful biological model system we have discovered key pathways for low exercise training response that may represent novel targets for the treatment of metabolic disease.
2014-05-23 | GSE57880 | GEO
Project description:We have previously demonstrated that the inhibitory effect of metformin on skeletal muscle complex-I linked mitochondrial respiration was associated with attenuated improvements in whole-body insulin sensitivity and cardiorespiratory fitness after aerobic exercise training (AET) in older adults. However, the mechanism(s) by which metformin impacts skeletal muscle adaptations to aerobic exercise remains unclear. To understand potential mechanisms associated with the inhibitory effect of metformin on mitochondrial adaptations to AET, we evaluated the skeletal muscle transcriptome, mitochondrial respiration, and hydrogen peroxide (H2O2) emissions in 7-month-old male C57BL6/J mice after 8-weeks of non-exercise sedentary control (SED) or progressive AET with and without metformin treatment. Metformin attenuated the number of differentially expressed genes by AET (975 vs. 449). Pathway analysis suggests that metformin suppressed several signal transduction pathways involved in oxidative capacity and cellular metabolism, including VEGF, AMPK, HIF-1α, and PI3K-AKT. Notably, the addition of metformin to AET suppressed 16 downstream targets of HIF-1α and was accompanied by metformin ameliorating the increase in mitochondrial respiratory capacity and ADP sensitivity after AET. However, neither AET nor AET+MET impacted mitochondrial H2O2 emitting potential. Given the central role of HIF-1α as an upstream transcriptional regulator of mitochondrial function and biogenesis, these results suggest that suppression of HIF-1α pathway by metformin could serve as a transcriptional regulatory node associated with the inhibitory role of metformin on skeletal muscle mitochondrial adaptations to aerobic exercise training.
2025-03-03 | GSE287490 | GEO
Project description:Gene expression changes in skeletal muscle following aerobic exercise training
| PRJNA578923 | ENA