Cross-Platform Transcriptomic Analysis of 40 Human and Rodent Skeletal Muscle Exerkines

Area of Science:

• Exercise physiology
• Molecular biology
• Systems biology

Background:

• Exercise triggers organism-wide molecular adaptations mediated by exerkines, which facilitate inter-organ communication.
• Understanding tissue-specific exerkine responses across species, exercise types, and sexes is crucial but limited.
• Exerkines are secreted factors enabling communication between tissues like skeletal muscle, adipose tissue, liver, and the brain.

Purpose of the Study:

• To systematically analyze skeletal muscle transcriptomic responses of 40 exerkines.
• To compare exerkine regulation across humans, mice, and rats under various exercise conditions.
• To identify conserved, non-conserved, and discordant exerkines, and their dependence on exercise modality or sex.

Main Methods:

• Systematic analysis of skeletal muscle transcriptomic data from three public datasets (MetaMEx, Extrameta, MoTrPAC).
• Review of exerkine-specific regulation in humans, mice, and rats across acute/chronic exercise and inactivity.
• Determination of conserved, non-conserved, and discordant exerkines across species, exercise modalities, and sexes.

Main Results:

• Substantial heterogeneity observed in skeletal muscle transcriptomic exerkine regulation.
• Only a small subset of exerkines demonstrated conserved changes across species.
• Significant variations in exerkine regulation were noted depending on exercise modality and sex.

Conclusions:

• Skeletal muscle exerkine regulation shows considerable species-specific differences, with limited conservation.
• Current transcriptomic data limits understanding of protein-level changes and functional exerkine activity.
• Multi-species and multi-condition approaches are essential for selecting exerkines as biomarkers or therapeutic targets.