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

Abstract

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.

Skeletal muscle BMAL1 is necessary for transcriptional adaptation of local and peripheral tissues in response to endurance exercise training

“…Genes encoding the negative limb of the TTFL have been shown to be responsive to acute exercise/muscle contraction (e.g., Pers, Nfil3) [9][10][11][12][13][14][15][16] and exercising at different times of the day is known to lead to unique metabolomic and transcriptional outcomes [17][18][19][20]. Exercise training also directly impacts the circadian transcriptome, by increasing the number of clock output genes [21,22].…”