Transcriptomic Signatures and Upstream Regulation in Human Skeletal Muscle Adapted to Disuse and Aerobic Exercise.

Pavel A Makhnovskii,Roman O Bokov,Daniil V Popov,Fedor A Kolpakov

doi:10.3390/ijms22031208

Abstract

Inactivity is associated with the development of numerous disorders. Regular aerobic exercise is broadly used as a key intervention to prevent and treat these pathological conditions. In our meta-analysis we aimed to identify and compare (i) the transcriptomic signatures related to disuse, regular and acute aerobic exercise in human skeletal muscle and (ii) the biological effects and transcription factors associated with these transcriptomic changes. A standardized workflow with robust cut-off criteria was used to analyze 27 transcriptomic datasets for the vastus lateralis muscle of healthy humans subjected to disuse, regular and acute aerobic exercise. We evaluated the role of transcriptional regulation in the phenotypic changes described in the literature. The responses to chronic interventions (disuse and regular training) partially correspond to the phenotypic effects. Acute exercise induces changes that are mainly related to the regulation of gene expression, including a strong enrichment of several transcription factors (most of which are related to the ATF/CREB/AP-1 superfamily) and a massive increase in the expression levels of genes encoding transcription factors and co-activators. Overall, the adaptation strategies of skeletal muscle to decreased and increased levels of physical activity differ in direction and demonstrate qualitative differences that are closely associated with the activation of different sets of transcription factors.

Highlights

Skeletal muscle tissue makes up more than a third of the adult human body mass playing a key role in fat and carbohydrate metabolism and positively regulating the functions of various tissues by acting as a secretory organ [1]
We identified several hundred genes related to each intervention and, for the first time, examined the dynamics of the transcriptomic responses to acute aerobic exercise (Table 1)
Using the standardized workflow and pressed the human muscle during (disuse, regular aerobic training cut-off criteria (Table S1)

Summary

Introduction

Skeletal muscle tissue makes up more than a third of the adult human body mass playing a key role in fat and carbohydrate metabolism and positively regulating the functions of various tissues by acting as a secretory organ [1]. Especially aerobic exercise, is broadly used as a key intervention to prevent and treat these pathological conditions (reviewed in [5]). Understanding the molecular mechanisms underlying skeletal muscle (dis)adaptation to inactivity and aerobic exercise is of fundamental importance. Examination of transcriptomic responses to an intervention provides a unique opportunity to assess the directions of adaptive changes and predict the underlying molecular mechanisms. Transcriptomic approaches can be used to (i) evaluate changes in the expression levels of genes of interest, (ii) predict biological effects associated with the expression of multiple genes with known and unknown functions and (iii) predict upstream regulators associated with the transcriptomic responses

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Methods

Discussion

Conclusion