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Simplified data access on human skeletal muscle transcriptome responses to differentiated exercise.

ABSTRACT: Few studies have investigated exercise-induced global gene expression responses in human skeletal muscle and these have typically focused at one specific mode of exercise and not implemented non-exercise control models. However, interpretation on effects of differentiated exercise necessitate direct comparison between essentially different modes of exercise and the ability to identify true exercise effect, necessitate implementation of independent non-exercise control subjects. Furthermore, muscle transcriptome data made available through previous exercise studies can be difficult to extract and interpret by individuals that are inexperienced with bioinformatics procedures. In a comparative study, we therefore; (1) investigated the human skeletal muscle transcriptome responses to differentiated exercise and non-exercise control intervention, and; (2) set out to develop a straightforward search tool to allow for easy access and interpretation of our data. We provide a simple-to-use spread sheet containing transcriptome data allowing other investigators to easily see how mRNA of their gene(s) of interest behave in skeletal muscle following exercise, both endurance, resistance and non-exercise, to better aid hypothesis-driven question in this field of research.

SUBMITTER: Vissing K

PROVIDER: S-EPMC4432635 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Simplified data access on human skeletal muscle transcriptome responses to differentiated exercise.

Vissing Kristian K Schjerling Peter P

Scientific data 20141125

Few studies have investigated exercise-induced global gene expression responses in human skeletal muscle and these have typically focused at one specific mode of exercise and not implemented non-exercise control models. However, interpretation on effects of differentiated exercise necessitate direct comparison between essentially different modes of exercise and the ability to identify true exercise effect, necessitate implementation of independent non-exercise control subjects. Furthermore, musc ...[more]

PMID: 25984345

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Project description:ObjectiveThe immediate signals that couple exercise to metabolic adaptations are incompletely understood. Nicotinamide adenine dinucleotide phosphate oxidase 4 (Nox4) produces reactive oxygen species (ROS) and plays a significant role in metabolic and vascular adaptation during stress conditions. Our objective was to determine the role of Nox4 in exercise-induced skeletal muscle metabolism.MethodsMice were subjected to acute exercise to assess their immediate responses. mRNA and protein expression responses to Nox4 and hydrogen peroxide (H2O2) were measured by qPCR and immunoblotting. Functional metabolic flux was measured via ex vivo fatty acid and glucose oxidation assays using 14C-labeled palmitate and glucose, respectively. A chronic exercise regimen was also utilized and the time to exhaustion along with key markers of exercise adaptation (skeletal muscle citrate synthase and beta-hydroxyacyl-coA-dehydrogenase activity) were measured. Endothelial-specific Nox4-deficient mice were then subjected to the same acute exercise regimen and their subsequent substrate oxidation was measured.ResultsWe identified key exercise-responsive metabolic genes that depend on H2O2 and Nox4 using catalase and Nox4-deficient mice. Nox4 was required for the expression of uncoupling protein 3 (Ucp3), hexokinase 2 (Hk2), and pyruvate dehydrogenase kinase 4 (Pdk4), but not the expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (Pgc-1α). Global Nox4 deletion resulted in decreased UCP3 protein expression and impaired glucose and fatty acid oxidization in response to acute exercise. Furthermore, Nox4-deficient mice demonstrated impaired adaptation to chronic exercise as measured by the time to exhaustion and activity of skeletal muscle citrate synthase and beta-hydroxyacyl-coA-dehydrogenase. Importantly, mice deficient in endothelial-Nox4 similarly demonstrated attenuated glucose and fatty acid oxidation following acute exercise.ConclusionsWe report that H2O2 and Nox4 promote immediate responses to exercise in skeletal muscle. Glucose and fatty acid oxidation were blunted in the Nox4-deficient mice post-exercise, potentially through regulation of UCP3 expression. Our data demonstrate that endothelial-Nox4 is required for glucose and fatty acid oxidation, suggesting inter-tissue cross-talk between the endothelium and skeletal muscle in response to exercise.

Dataset Information

Simplified data access on human skeletal muscle transcriptome responses to differentiated exercise.

Publications

Simplified data access on human skeletal muscle transcriptome responses to differentiated exercise.

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