Exercise Training Effects on Human Skeletal Muscle DNA Methylation
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Dawn Coletta
PROVIDER: E-MTAB-11282 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2014-09-10 | E-GEOD-58250 | biostudies-arrayexpress
Project description:Regular endurance exercise training induces beneficial functional and health effects in human skeletal muscle. The putative contribution to the training response of the epigenome as a mediator between genes and environment has not been clarified. Here we investigated the contribution of DNA methylation and associated transcriptomic changes in a well-controlled human intervention study. Training effects were mirrored by significant alterations in DNA methylation and gene expression in regions with a homogeneous muscle energetics and remodeling ontology. Differential DNA methylation predominantly occurred in regulatory enhancer regions, where known binding motifs of MRF, MEF2 and ETS proteins were identified. A transcriptional network analysis revealed modules harboring distinct ontologies, and interestingly the overall direction of the changes of methylation within each module was inversely correlated to expression changes. In conclusion, we show that highly consistent and associated modifications in methylation and expression, concordant with observed health-enhancing phenotypic adaptations, are induced by a physiological stimulus. DNA samples from vastus lateralis muscle bisopsies were included in the study. Specifically, 23 subjects performed three months of supervised endurance training. Biospies were taken at rest, before and after training. DNA methylation levels were profiled using Illumina 450K arrays.
2014-11-04 | E-GEOD-60655 | biostudies-arrayexpress
Project description:This study was undertaken to test the hypothesis that short term exposure (4 hours) to physiologic hyperinsulinemia in normal, healthy subjects without a family history of diabetes would induce a low grade inflammatory response, independently of glycemic status. We performed euglycemic hyperinsulinemic (80 mU/m2/min) clamps in 12 healthy, insulin sensitive subjects with no family history of diabetes followed by biopsies of the vastus lateralis muscle taken basally and after 30 and 240 minutes of insulin infusion. Gene expression profiles were generated using Affymetrix HG-U133A arrays. No probe sets had significantly altered expression at 30 minutes of the insulin clamp, but 121 probe sets (117 upregulated and 4 downregulated) were significantly altered after 240 minutes. Hyperinsulinemia in normal, healthy human subjects increased the mRNAs for a number of inflammatory genes and transcription factors. Microarray and quantitative RT-PCR revealed the upregulation of chemokine, cc motif, ligand 2 (CCL2), CCL8, thrombomodulin (THBD), ras-related associated with diabetes (RRAD), metallothionein (MT), and serum/glucocorticoid regulated kinase (SGK), and downregulation of CITED2 (a CREB-binding protein-interacting transactivator), a known coactivator of PPAR-alpha. Interestingly, SGK and CITED2 are located at chromosome 6q23, where we previously detected strong linkage to hyperinsulinemia. A control saline infusion performed on 3 normal, healthy subjects without a family history of diabetes demonstrated that the genes altered following the euglycemic-hyperinsulinemic clamp were due to insulin and independent of biopsy removal. This study demonstrates that insulin acutely regulates the expression of genes involved in inflammation and transcription, and identifies several candidate genes/pathways for further investigation. Experiment Overall Design: Twelve subjects received a vastus lateralis muscle biopsy followed by a 180-min euglycemic, hyperinsulinemic (80 mU/m2.min) clamp. Muscle biopsies from each subject were homogenized in RNAStat solution (Tel-Test Inc., Friendswood, TX), using a Polytron homogenizer (Brinkmann Instruments Westbury, NY). Total RNA was purified with RNeasy and DNase I treatment (Qiagen, Chatsworth, CA). RNA was prepared for hybridization to Affymetrix (Santa Clara, CA) HG-U133A arrays according to the manufacturerâs instructions.
2008-06-16 | E-GEOD-9105 | biostudies-arrayexpress
Project description:Time course of mRNA after 30 minutes of endurance exercise at simulated altitude of 4000 m in an untrained or six weeks trained state of six subjects. Time course of mRNA after 30 minutes of endurance exercise at simulated altitude of 4000 m in an untrained (1) or six weeks trained state (2) of six subjects (Hoxxx) Ho981: (1) GSM343213, GSM343214, GSM343215, GSM343216; (2) GSM343217, GSM343218, GSM343219, GSM343220 Ho982: (1) GSM343221, GSM343222, GSM343223, GSM343224; (2) GSM343225, GSM343226, GSM343227, GSM343228 Ho984: (1) GSM343229, GSM343230, GSM343231, GSM343232; (2) GSM343233, GSM343234, GSM343235, GSM343236 Ho994: (1) GSM343237, GSM343238, GSM343239, GSM343240; (2) GSM343241, GSM343242, GSM343243, GSM343244 Ho998: (1) GSM343245, GSM343246, GSM343247, GSM343248; (2) GSM343249, GSM343250, GSM343251, GSM343252 Ho996: (1) GSM343253, GSM343254, GSM343255, GSM343256 Keywords: time-course
2009-11-15 | E-GEOD-13623 | biostudies-arrayexpress
Project description:Genome-wide DNA methylation profiling of healthy young men following a control and high-fat overfeeding diet using Illumina's Infinium 27k Human DNA methylation Beadchip v. 1.2. DNA methylation profiles were obtained for 27,578 CpG sites in human skeletal muscle. Randomized cross-over desgin, where all subjects receieved both treatments (control and high-fat overfeeding diet). Biopsies were obtained from 23 different individuals amounting to 22 samples following the control diet and 22 samples following the high-fat overfeeding diet (paired n=21). Bisulphite converted DNA from the 44 samples were hybridised to the Illumina Infinium 27k Human Methylation Beadchip.
2012-09-12 | E-GEOD-36166 | biostudies-arrayexpress
Project description:Septic patients treated in the intensive care unit (ICU) often develop multiple organ failure including persistent skeletal muscle dysfunction which results in the patientâs protracted recovery process. We have demonstrated that muscle mitochondrial enzyme activities are impaired in septic ICU patients resulting in decreased cellular energy which will interfere with muscle function and metabolism. Here we use detailed phenotyping and genomics to elucidate mechanisms leading to these impairments. Methodology/Principle Findings Utilising biopsy material from seventeen patients and ten age-matched controls we demonstrate that neither mitochondrial in vivo protein synthesis nor expression of mitochondrial genes are compromised. Indeed, there was partial activation of the mitochondrial biogenesis pathway involving NRF2?/GABP and its target genes TFAM, TFB1M and TFB2M yet clearly this failed to maintain mitochondrial function. We therefore utilised transcript profiling and pathway analysis of ICU patient skeletal muscle to generate insight into the molecular defects driving loss of muscle function and metabolic homeostasis. Gene ontology analysis of Affymetrix analysis demonstrated substantial loss of muscle specific genes, a global oxidative stress response related to most probably cytokine signalling, altered insulin related signalling and a substantial overlap between patients and muscle wasting/inflammatory animal models. MicroRNA 21 processing appeared defective suggesting that post-transcriptional protein synthesis regulation is altered by disruption of tissue microRNA expression. Finally, we were able to demonstrate that the phenotype of skeletal muscle in ICU patients is not merely one of inactivity, it appears to be an actively remodelling tissue, influenced by several mediators, all of which may be open to manipulation with the aim to improve clinical outcome. Conclusions/Significance This first combined protein and transcriptome based analysis of human skeletal muscle obtained from septic patients demonstrated that losses of mitochondria and muscle mass are accompanied by sustained protein synthesis (anabolic process) while dysregulation of transcription programmes appears to fail to compensate for increased damage and proteolysis. Our analysis identified both validated and novel clinically tractable targets to manipulate these failing processes and pursuit of these could lead to new potential treatments. Experiment Overall Design: 13 septic samples, 8 controls
2008-11-22 | E-GEOD-13205 | biostudies-arrayexpress
Project description:We investigated the genomic and physiological impact of acute sleep loss in peripheral tissues, by obtaining adipose tissue and skeletal muscle after one night of sleep loss and after one full night of sleep. Processed data (M-values for probes not overlapping SNPs) only. Raw data will be submitted to EGA.
2018-06-30 | E-MTAB-6908 | biostudies-arrayexpress
Project description:With the population of older and overweight individuals on the rise in the Western world, there is an ever greater need to slow the aging processes and reduce the burden of age-associated chronic disease that would significantly improve the quality of human life and reduce economic costs. Caloric restriction (CR), is the most robust and reproducible intervention known to delay aging and to improve healthspan and lifespan across species (1); however, whether this intervention can extend lifespan in humans is still unknown. Here we report that rats and humans exhibit similar responses to long-term CR at both the physiological and molecular levels. CR induced broad phenotypic similarities in both species such as reduced body weight, reduced fat mass and increased the ratio of muscle to fat. Likewise, CR evoked similar species-independent responses in the transcriptional profiles of skeletal muscle. This common signature consisted of three key pathways typically associated with improved health and survival: IGF-1/insulin signaling, mitochondrial biogenesis and inflammation. To our knowledge, these are the first results to demonstrate that long-term CR induces a similar transcriptional profile in two very divergent species, suggesting that such similarities may also translate to lifespan-extending effects in humans as is known to occur in rodents. These findings provide insight into the shared molecular mechanisms elicited by CR and highlight promising pathways for therapeutic targets to combat age-related diseases and promote longevity in humans. Percutaneous biopsy specimens of vastus lateralis muscle were taken from 15 Human subjects from a group of middle-aged (58.7±7.4 yrs.), weight-stable members of the Calorie Restriction Society who have been practicing ~30% CR with adequate nutrition (at least 100% of RDI for each nutrient) for an average of 9.6 years and 10 age matched controls that were eating a typical Western diet. Total RNA was extracted from the skeletal muscle using Trizol Reagent (Invitrogen, Carlsbad, CA) following the manufacturer’s instructions, RNA quality and quantity was checked using an Agilent 2100 Bio-analyzer and the RNA 6000 nano-chips (Agilent Technologies, Palo Alto, CA). Total RNA samples were biotin labeled and hybridized to Sentrix Human HT-12, v3 Expression BeadChips (Illumina, San Diego, CA), following Illumina protocols. Arrays were washed, stained and scanned using an Illumina BeadArray 500GX reader. Microarray florescent signals were extracted using the Illumina GenomeStudio Gene Expression software(v1.6.0) and any spots at or below the background were filtered using an Illumina detection p-value of 0.02 and above. The natural log of all remaining scores were used to find the avg and std of each array and the z-score normalization was calculated . Correlation analysis, sample clustering analysis and principal component analysis include all of probes are performed to identify/exclude any possible outliners. The resulting dataset was next analyzed with DIANE 6.0, a spreadsheet based microarray analysis program. Gene set enrichment analysis use gene expression values or gene expression change values for all of the genes in the microarray. Parametric analysis of gene set enrichment (PAGE) was used [pubmed 20682848] for gene set analysis.
2013-08-01 | E-GEOD-38012 | biostudies-arrayexpress
Project description:Genome-wide DNA methylation profiling of young men born with low birth weight following a control and high-fat overfeeding diet using Illumina's Infinium 27k Human DNA methylation Beadchip v. 1.2. DNA methylation profiles were obtained for 27,578 CpG sites in human skeletal muscle. Randomized cross-over desgin, where all subjects receieved both treatments (control and high-fat overfeeding diet). Biopsies were obtained from 17 different individuals amounting to 16 samples following the control diet and 15 samples following the high-fat overfeeding diet (paired n=14). Bisulphite converted DNA from the 31 samples were hybridised to the Illumina Infinium 27k Human Methylation Beadchip.
2014-01-01 | E-GEOD-40798 | biostudies-arrayexpress
Project description:Methylation analysis of 12 corresponding pairs of tumor endothelial cells (TECs) and normal endothelial cells (NECs) isolated from human colorectal carcinoma (CRC) patients with different prognostic tumor microenvironments (TMEs: Th1-TME vs Control-TME): High and low GBP-1 expression in the tumors detected by IHC was used to categorize the patient-derived cells into Th1-TME and Control-TME (compare Naschberger et al, J Clin Invest 2016 and Naschberger et al, Int J Cancer 2008). Isolation of the samples was done according to Naschberger et al, JoVE 2018. The analysis is paralleled by omics-analysis of the same cell cultures at the transcriptome (E-MTAB-10465) and genome level (E-MEXP-3993).
2023-05-01 | E-MTAB-10467 | biostudies-arrayexpress