Unknown,Transcriptomics,Genomics,Proteomics

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Near-whole-genome transcriptome analysis of gene expression in human skeletal muscle tissue at baseline in obese individuals with Type 2 Diabetes

ABSTRACT: Analysis of gene expression associated with exercise response. The hypothesis tested was that individuals with Type 2 Diabetes that failed to demonstrate exercise-induced metabolic improvements would also reflect this lack of response in their skeletal muscle transcriptional profile at baseline. Of 186 genes identified by microarray analysis, 70% were upregulated in Responders and downregulated in Non-responders. Several genes involved in substrate metabolism and mitochondrial biogenesis differed significantly between the groups at baseline. This differential baseline gene expression indicated that Non-responders had blunted oxidative capacity. Total RNA extracted from baseline samples of skeletal muscle of obese individuals with Type 2 Diabetes who were characterized as either Responders or Non-responders was examined for differential expression of exercise response-assocated genes.

ORGANISM(S): Homo sapiens

SUBMITTER: Lauren Sparks

PROVIDER: E-GEOD-74782 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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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.