Temporal Multi-Omic Analysis Uncovers Sex-Biased Molecular Programs Underlying Skeletal Muscle Adaptation to...

Area of Science:

• Exercise physiology and molecular biology
• Skeletal muscle adaptation research
• Multi-omics analysis of physical activity

Background:

• Exercise training confers significant health benefits, largely mediated by skeletal muscle adaptations.
• Understanding the molecular regulators of these adaptations, especially sex-specific differences, is crucial but incomplete.
• Skeletal muscle's response to exercise is fundamental to overall health and disease risk reduction.

Purpose of the Study:

• To identify shared and sex-specific multi-omic molecular responses to endurance training in rat skeletal muscle.
• To correlate these molecular adaptations with observed phenotypic changes.
• To elucidate the role of post-translational modifications in exercise-induced skeletal muscle adaptation.

Main Methods:

• Utilized skeletal muscle multi-omics data from the Molecular Transducers of Physical Activity Consortium (MoTrPAC).
• Analyzed endurance-trained male and female rats at multiple time points (1, 2, 4, 8 weeks).
• Integrated transcriptomic, proteomic, and post-translational modification data.

Main Results:

• Identified largely conserved transcriptomic and proteomic pathway enrichments in the gastrocnemius muscle, correlating with human exercise responses.
• Uncovered sex-consistent post-translational modifications, such as decreased MYH2 oxidation and HADHA deacetylation.
• Revealed sex-specific remodeling in acetylome, redox proteome, and phosphoproteome; females showed enhanced mitochondrial efficiency and redox buffering, while males exhibited earlier mitochondrial transcript induction and mTOR activation.

Conclusions:

• A significant portion of skeletal muscle adaptation to endurance training is conserved between sexes.
• Distinct and nuanced sex-specific adaptations exist, particularly at the post-translational regulation level.
• This research provides a comprehensive molecular map of exercise adaptation, highlighting sex as a key biological variable.