Low responders to endurance training exhibit impaired hypertrophy and divergent biological process responses in rat skeletal muscle

Divergent skeletal muscle phenotypes result from chronic resistance‐type versus endurance‐type contraction, reflecting the principle of training specificity. Aim: To determine whether there is a common set of genetic factors that influence skeletal muscle adaptation to divergent contractile stimuli. Methods: Female rats were obtained from a genetically heterogenous rat population and were selectively bred from high responders to endurance training (HRT) or low responders to endurance training (LRT; n = 6/group; generation 19). Both groups underwent 14‐d synergist ablation to induce functional overload of the plantaris muscle prior to comparison to non‐overload controls of the same phenotype. RNA sequencing was performed to identify Gene Ontology Biological Processes with differential (LRT vs HRT) gene set enrichment. Results: Running distance, determined in advance of synergist ablation, increased in response to aerobic training in HRT but not LRT (65 ±26% versus ‐6 ±18%, mean ± SD, P<0.0001). The hypertrophy response to functional overload was attenuated in LRT versus HRT (20.1 ±5.6% versus 41.6 ±16.1%, P = 0.015). Between‐group differences were observed in the magnitude of response of 96 upregulated and 101 downregulated pathways. A further 27 pathways showed contrasting upregulation or downregulation in LRT versus HRT in response to functional overload. Conclusions: Low responders to aerobic endurance training were also low responders for compensatory hypertrophy, and attenuated hypertrophy was associated with differential gene set regulation. Our findings suggest that genetic factors that underpin aerobic training maladaptation may also dysregulate the transcriptional regulation of biological processes that contribute to adaptation to mechanical overload.