Low responders to endurance training exhibit greater atrophy
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ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE159861 | GEO | 2021/10/24
REPOSITORIES: GEO
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Project description:Divergent skeletal muscle phenotypes result from chronic resistance-type- versus endurance-type contraction, reflecting the principle of training specificity. However, it is unclear whether there is a common set of genetic factors that influence skeletal muscle adaptation to different modes of training. Female rats were obtained from out-bred lines selectively bred from high responders to endurance training (HRT) or low responders to endurance training (LRT; n=6/group; generation 19). Both groups underwent 14 d of synergist ablation to induce functional overload of the plantaris muscle prior to comparison to non-overload controls of the same genotype. RNA sequencing was performed to identify Gene Ontology Biological Processes with differential (LRT vs HRT) gene set enrichment. Running distance, determined well in advance of synergist ablation, increased in response to aerobic training in HRT but not LRT (65 ±26% versus -6 ±18%, respectively, mean ±SD, p<0.0001). The hypertrophy response to functional overload was attenuated in LRT versus HRT (20.1 ±5.6% versus 41.6 ±16.1%, respectively, P = 0.015). There were between-group differences in the magnitude of response of 96 upregulated- and 101 downregulated pathways. A further 27 pathways showed contrasting upregulation or downregulation in LRT versus HRT in response to functional overload. In conclusion, low responders to aerobic endurance training were also low responders for compensatory hypertrophy, and attenuated hypertrophy was associated with differential gene expression. Thus, our findings suggest that genetic factors that underpin aerobic training maladaptation may also dysregulate the transcriptional activity of biological processes that contribute to adaptation to mechanical overload.
2020-12-31 | GSE156724 | GEO
Project description:Low responders to endurance training exhibit greater atrophy
| PRJNA670700 | ENA
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:p53 regulates a distinct subset of skeletal muscle mRNAs during immobilization-induced skeletal muscle atrophy For additional details see Fox et al, p53 and ATF4 mediate distinct and additive pathways to skeletal muscle atrophy during limb immobilization. Am J Physiol Endocrinol Metab. 2014 Aug 1;307(3):E245-61. Bilateral tibialis anterior muscles were harvested at three days for the following conditions: 1) hindlimb immobilization of C57BL/6 mice; 2) hindlimb immobilization of p53 mKO and littermate control mice; 3) transfection of wild type mice with p53 plasmid or control plasmid
2014-11-05 | E-GEOD-62897 | 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:Aerobic exercise capacity is a strong predictor of disease and survivability but the utility of exercise intervention is largely dependent on how one’s genome interacts with an exercise-training environment. A newly developed rat model selectively bred for inherited differences in response to aerobic exercise training shows to be a useful resource to sort out the networks of genes responsible for signalling exercise-induced changes that benefit cardiac function. Animals The study consisted of four groups: 1) HRT trained rats (HRT-T), 2) LRT trained rats (LRT-T) 3) HRT untrained sedentary rats (HRT-S) and 4) LRT untrained sedentary rats (LRT-S) (n=5 in each group). Experimental protocols were approved by the Institutional Animal Research Ethics Council, Norway. Sample collection Left ventricle tissue was snap-frozen in liquid nitrogen and stored at -80oC to time of analysis. RNA isolation RNA was isolated from the left ventricle (20 mg) with the mirVana RNA isolation kit (Ambion) according to the manufacturer's instructions. RNA integrity, purity and quantity were assessed by Bioanalyzer (Agilent Technologies, Santa Clara, US) and Nanodrop (NanoDrop Technologies, Baltimore, US). The concentration of total RNA was measured by Nanodrop with ultraviolet spectrophotometry at 260/280 nm. RNA quality was assessed by electrophoresis on Bioanalyzer chips (Agilent Technologies, Santa Clara, US). Only samples with a 260/280-ratio of more than 1.8, and RNA integrity number (RIN) value above 8 was analyzed. Microarray analysis Samples were hybridized to Applied Biosystems Rat Genome Survey chips v.1.0. All samples were labelled at the same time, and hybridised over two days. The biological groups were balanced between the two hybridisation batches and the samples randomly distributed within this format. Samples were analyzed by the Applied Biosystems 1700 Array Expression System. The following threes comparisons were done: A: HRT-S vs. LRT-S B: HRT-S vs. HRT-T C: LRT-S vs. LRT-T Differentially expressed gene analysis The data files from the AB 1700 Chemiluminescent Microarray Analyzer Software were processed using J-Express Pro v.2.8. The signal intensity values were extracted per spot, and all flagged and control spots were filtered out. Before compiled into an expression profile data matrix, all arrays were quantile normalized to be comparable. Genes with at most 20% missing values were allowed in the final dataset. The signal intensities in the dataset were further log transformed, and missing values were replaced using the method LSimpute Adaptive. The search for differentially expressed genes was performed both on a single gene and gene set level. Rank Product was used to look for differentially expressed genes on a gene by gene basis, while Gene Set Enrichment Analysis (GSEA) was used to look for sets of genes sharing common characteristics that were differentially expressed between the classes examined. Gene sets were created using the Panther Biological Processes (241 gene sets) and Panther Molcular Functions (252 gene sets). This information was extracted from the Applied Biosystems Human Annotation File, dated September 30th 2006, with updated information from a Panther search carried out on February 1st 2008. Gene sets smaller than 15 and larger than 500 were excluded from the GSEA. GSEA First the genes were ranked according to Golub score, which t is the default method for GSEA. Next an enrichment score (ES) was calculated for each gene set. For instance, when calculating the ES for the gene set “T-cell mediated immunity”, GSEA starts by looking at the gene ranked on top of the genelist. If this gene is a member of T-cell mediated immunity, a positive score is added to the ES, otherwise a negative score is added. Then the next gene on the gene list is evaluated and the ES is updated. This process is repeated for every gene in the entire gene list. The green line in Figure 1 shows how the value of ES changes when evaluating the genes in the ranked list. The maximum value obtained during this “walk” is used as ES for the gene set. Also worth noting is that the positive score that is added to the enrichment score is weigthed, so that a higher score is added when a gene higher on the ranked list is found to be a member of the gene set than when a gene lower on the ranked list is marked with a hit. Therefore, a high ES means that the gene set is overrepresented towards the top of the ranked list. Gene sets with less than 10 members or more than 500 members were removed from the analysis.
2012-01-01 | E-GEOD-20997 | biostudies-arrayexpress
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: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 TGFM-NM-2 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. Cardiac and skeletal muscle from 3 high and 3 low responder rats were examined for differential miRNA expression using Exiqon microarrays
2014-05-23 | E-GEOD-57880 | biostudies-arrayexpress
Project description:Skeletal muscle unloading due to joint immobilization induces skeletal muscle atrophy. However, the skeletal muscle proteome response to limb immobilization has not been investigated using SWATH methods. This study quantitatively characterized the muscle proteome at baseline, and after 3 and 14 d of unilateral lower limb (knee-brace) immobilization in 18 healthy young men (25.4 ±5.5 y, 81.2 ±11.6 kg). All muscle biopsies were obtained from the vastus lateralis muscle. Unilateral lower limb immobilization was preceded by four-weeks of exercise training to standardise acute training history, and 7 days of dietary provision to standardise energy/macronutrient intake. Dietary intake was also standardised/provided throughout the 14 d immobilization period.
2022-08-25 | PXD034908 | Pride
Project description:Combining resistance and endurance exercises in a training regime (concurrent training) can impair improvements in muscle hypertrophy, strength, and power compared to resistance training alone. Here we aimed to characterize skeletal muscle transcriptomic changes following chronic concurrent training to determine whether contraction-induced gene expression may reveal molecular underpinnings explaining impaired adaptations. Eighteen young, healthy male participants underwent 12 weeks of resistance, endurance, or concurrent training. Maximal strength, aerobic capacity, and anaerobic power were assessed. Transcriptomics were performed on skeletal muscle biopsies obtained pre and post-intervention. Improvements to maximal anaerobic power are impaired with concurrent and endurance training. Gene expression related to plasma membrane structures was enriched while gene expression related to regulation of mRNA processing and protein degradation was suppressed with concurrent training. Considerable overlap of gene expression related to extracellular matrix remodeling was observed between concurrent and endurance training. Our results provide the first comprehensive comparison of unique and overlapping gene sets enriched following chronic resistance, endurance, and concurrent training, and reveals pathways that may have implications in relation to impaired adaptations when undertaking concurrent training.
2023-04-01 | GSE137832 | GEO