High and low exercise responders
Ontology highlight
ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE20997 | GEO | 2012/01/01
SECONDARY ACCESSION(S): PRJNA124515
REPOSITORIES: GEO
Similar Datasets
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:To investigate the effect of aerobic exercise on liver injury in nonalcoholic steatohepatitis (NASH), we established a NASH model induced by atherosclerotic (Ath) diet and intervened with aerobic exercise training.
2023-01-11 | GSE217155 | 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: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 disuse. 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 3 d of hindlimb immobilization to induce atrophy of the plantaris and soleus muscles prior to comparison to non-immobilization 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 hindlimb immobilization, increased in response to aerobic training in HRT but not LRT. The atrophy response to hindlimb immobilization was exaggerated in LRT versus HRT. There were between-group differences for 140 processes in plantaris muscle and 118 processes in soleus muscle. In conclusion, low responders to aerobic endurance training exhibited exaggerated atrophy, and this 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 hindlimb immobilization.
2021-10-24 | GSE159861 | GEO
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:Skeletal muscle adapts to exercise training of various modes, intensities and durations with a programmed gene expression response. This study dissects the independent and combined effects of exercise mode, intensity and duration to identify which exercise has the most positive effects on skeletal muscle health. Full details on exercise groups can be found in: Kraus et al Med Sci Sports Exerc. 2001 Oct;33(10):1774-84 and Bateman et al Am J Cardiol. 2011 Sep 15;108(6):838-44. This study uses a middle aged group of subjects that have 3+ markers of metabolic syndrome. One group remains an inactive control, while 5 groups undergo 9 mo supervised exercise training. Exercise groups are as follows: Inactive control (group B); Mild aerobic exercise - low amount/mod intensity (group A); Moderate aerobic exercise - low amt/vig intensity (group D); High aerobic exercise - high amt/vig intensity (group C); resistance training only (group F); and mod aerobic + resistance training (group E). Each group has 10 subjects (5 men and 5 women), however 3 subjects failed array QC, leaving 8 subjects in group E and 9 subjects in group F. Data were all analyzed pre to post training in a RM ANCOVA, covaried for age and sex or regression to determine genotype/phenotype interactions.
2015-05-14 | E-GEOD-48278 | biostudies-arrayexpress
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 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