Conserved and species-specific transcriptional responses to daily programmed resistance exercise in rat and mouse.

Mice are often used in gain or loss of function studies to understand how genes regulate metabolism and adaptation to exercise in skeletal muscle. Once-daily resistance training with electrical nerve stimulation produces hypertrophy of the dorsiflexors in rat, but not in mouse. Using implantable pulse generators, we assessed the acute transcriptional response (1-h post-exercise) after 2, 10, and 20 days of training in free-living mice and rats using identical nerve stimulation paradigms. RNA sequencing revealed strong concordance in the timecourse of many transcriptional responses in the tibialis anterior muscles of both species including responses related to "stress responses/immediate-early genes, and "collagen homeostasis," "ribosomal subunits," "autophagy," and "focal adhesion." However, pathways associated with energy metabolism including "carbon metabolism," "oxidative phosphorylation," "mitochondrial translation," "propanoate metabolism," and "valine, leucine, and isoleucine degradation" were oppositely regulated between species. These pathways were suppressed in the rat but upregulated in the mouse. Our transcriptional analysis suggests that although many pathways associated with growth show remarkable similarities between species, the absence of an actual growth response in the mouse may be because the mouse prioritizes energy metabolism, specifically the replenishment of fuel stores and intermediate metabolites

Adaptation of the transcriptional response to resistance exercise over 4 weeks of daily training

We present the time course of change in the muscle transcriptome 1 h after the last exercise bout of a daily resistance training program lasting 2, 10, 20, or 30 days. Daily exercise in rat tibialis anterior muscles (5 sets of 10 repetitions over 20 min) induced progressive muscle growth that approached a new stable state after 30 days. The acute transcriptional response changed along with progressive adaptation of the muscle phenotype. For example, expression of type 2B myosin was silenced. Time courses recently synthesized from human exercise studies do not demonstrate so clearly the interplay between the acute exercise response and the longer-term consequences of repeated exercise. We highlight classes of transcripts and transcription factors whose expression increases during the growth phase and declines again as the muscle adapts to a new daily pattern of activity and reduces its rate of growth. Myc appears to play a central role