28-OR: Posttranslational Modifications in Skeletal Muscle Direct Divergent Metabolic Responses to Different Exercise Training Modes

Different exercise modes yield distinct metabolic outcomes, yet the underlying molecular mechanisms driving these exercise responses remain unclear. Here, we investigated the impact of post-translational modifications (PTM) to skeletal muscle proteins in response to 3 months of high intensity aerobic interval training (HIIT) and resistance exercise training (RT). Frozen muscle biopsy tissue was obtained from a sub-cohort of our previously published study which showed significantly enhanced insulin sensitivity following either HIIT (n=7) or RET (n=7). After digestion, peptides were isobarically labeled and either acetyl- or phospho-enriched and fractionated by high-performance liquid chromatography (HPLC). Mass spectra were measured using a Thermo Fusion Tribrid coupled to Ultimate 3000 HPCL, revealing global-, phospho-, and acetyl-proteomic responses in muscle to HIIT or RT. Reactome analysis was used to determine exercise-regulated PTM pathways. HIIT significantly (p-value <0.05, fold-change ≥ 0.3) increased the abundance of ~9% of the global proteome (444 proteins) and ~22% of the acetylproteome (504 peptides), with primarily global and acetyl modifications occurring on mitochondrial pathways. HIIT also significantly (P < 0.05) increased the abundance of the deacetylase, SIRT3, which was positively associated with mitochondrial respiration. RT significantly (p-value <0.05, fold-change ≥ 0.3) altered the abundance of ~3% of the global proteome (144 proteins) and ~7% of the phosphoproteome (817 peptides), with minimal effect on the acetylproteome (~1%). RT primarily regulated contractile function and muscle structure pathways. These results indicate that the divergent metabolic responses to HIIT or RT are related to differential PTM mechanisms that contribute to cardiometabolic outcomes.