Different resistance exercise loading paradigms similarly affect methylation status and mRNA expression patterns of myostatin-related genes in skeletal muscle
Authors: McIntosh Mason , Sexton Casey , Godwin Joshua , Ruple Bradley , Ziegenefuss Tim , Lopez Hector , Smith Ryan , Dwaraka Varun , Sharples Adam , Vann Christopher , Roberts Michael 
Published: May 2023

Although several resistance exercise studies have used bioinformatics platforms to identify the biological relevance of gene expression changes, these platforms seldom provide in-depth information on genes that have been mechanistically linked to skeletal muscle hypertrophy. Thus, we sought to perform a secondary analysis on a muscle transcriptomic dataset we previously collected involving two different bouts of resistance exercise. Previously trained college-aged males (n=11, training experience: 4±3 years) performed two resistance exercise bouts separated by one week. The higher-load bout (80fail) consisted of 4 sets of back squats and 4 sets of leg extensions to failure using 80% of their estimated one-repetition maximum. The lower-load bout (30fail) consisted of this same paradigm using 30% of their one-repetition maximum. Vastus lateralis muscle biopsies were collected before (PRE), 3 hours (3h), and 6 hours (6h) after each exercise bout, and bouts were separated by a one-week washout. Muscle mRNA was analyzed for genome-wide mRNA expression patterns using the Clariom S mRNA array. Based on an extensive literature search performed by us and others, the mRNA expression profile of gene candidates mechanistically associated with skeletal muscle hypertrophy (58 genes) was interrogated between 30fail and 80fail training. Select targets were further interrogated for associated protein expression and phospho-signaling events. Although none of the 58 skeletal muscle hypertrophy-associated gene targets demonstrated significant bout✕time point interactions, ~57% showed a significant time-only effect from PRE to 3h (15↑ and 18↓, p<0.01) and ~26% showed significant time-only effect from PRE to 6h (8↑ and 9↓, p<0.01). Genes related to myostatin signaling (9 genes) and mTORC1 signaling (9 genes) were well represented on the gene list. Compared to mTORC1 signaling mRNAs, a greater percentage of myostatin signaling-related mRNAs were dynamically altered post-exercise (i.e., significant time-only effects). There were increases in phospho (Thr389)/pan p70S6K (p=0.001; PRE to 3h) and follistatin protein levels (p=0.021; PRE to 6h) regardless of bout. No significant time effects or interactions were observed for phospho (Ser2448)/pan mTOR, phospho (Thr389)/pan AKT, phospho (Ser235/236)/pan rpS6, or myostatin protein levels. The data have multiple implications. First, performing lighter load and heavier load resistance exercise to failure elicits similar alterations in the mRNA responses of genes mechanistically associated with skeletal muscle hypertrophy and mTORC1 signaling. Second, acute resistance exercise predominantly affects the myostatin signaling pathway via transcriptional mechanisms and genes involved with mTORC1 signaling are less affected in this regard. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.