The influence of nutrients on mechanical overload-induced changes to skeletal muscle mRNA content

Mechanical overload and nutrients influence skeletal muscle phenotype, with the combination sometimes having a synergistic effect. Muscle phenotypes influenced by these stimuli are mediated in part by changes to the muscle mRNA signature. However, the mechanical overload-sensitive gene programs that are influenced by nutrients remain unclear. The purpose of this study was to identify mechanical overload-sensitive gene programs that are influenced by nutrients and identify potential tran-scription factors that may differentiate the change in mRNA in response to mechanical overload versus nutrients. Nutrient -deprived 12-wk-old male mice were randomized to remain fasted or allowed access to food. All mice underwent a single bout of unilateral high force contractions of the tibialis anterior (TA). Four hours postcontractions TA muscles were extracted and the content of 12 contraction-sensitive mRNAs was analyzed. The mRNA content of genes associated with transcription, PI3K-Akt sig-naling pathway, Z-disc, intracellular signal transduction, cell cycle, and amino acid transport was altered by contractions without the influence of nutrient consumption. Conversely, the mRNA content of genes associated with transcription, cell cycle, FoxO signaling pathway, and amino acid transport was altered by contractions with nutrition consumption influencing the change. We identified the signal transducer and activator of transcription 3 (STAT3) and activator protein 1 (AP-1) as transcription factors com-mon among mRNAs that were primarily altered by mechanical overload regardless of feeding. Overall, these data provide a deeper molecular basis for the specific muscle phenotypes exclusive to mechanical overload versus those regulated by the addition of nutrients.

Automated summary

Mechanical overload and nutrients can influence the phenotype of skeletal muscles, with mechanical overload primarily affecting mRNA signature and the influence of nutrients on gene programs remaining unclear. This study identified mechanical overload-sensitive gene programs influenced by nutrients and identified potential transcription factors that differentiate mRNA changes in response to mechanical overload and nutrients.