Abstract
Skeletal muscle atrophy is a physiological response to disuse, aging, and disease. We compared changes in muscle mass and the transcriptome profile after short-term immobilization in a divergent model of high and low responders to endurance training to identify biological processes associated with the early atrophy response. Female rats selectively bred for high response to endurance training (HRT) and low response to endurance training (LRT; n = 6/group; generation 19) underwent 3 day hindlimb cast immobilization to compare atrophy of plantaris and soleus muscles with line-matched controls (n = 6/group). RNA sequencing was utilized to identify Gene Ontology Biological Processes with differential gene set enrichment. Aerobic training performed prior to the intervention showed HRT improved running distance (+60.6 ± 29.6%), while LRT were unchanged (-0.3 ± 13.3%). Soleus atrophy was greater in LRT vs. HRT (-9.0 ±8.8 vs. 6.2 ±8.2%; P<0.05) and there was a similar trend in plantaris (-16.4 ±5.6% vs. -8.5 ±7.4%; P = 0.064). A total of 140 and 118 biological processes were differentially enriched in plantaris and soleus muscles, respectively. Soleus muscle exhibited divergent LRT and HRT responses in processes including autophagy and immune response. In plantaris, processes associated with protein ubiquitination, as well as the atrogenes (Trim63 and Fbxo32), were more positively enriched in LRT. Overall, LRT demonstrate exacerbated atrophy compared to HRT, associated with differential gene enrichments of biological processes. This indicates that genetic factors that result in divergent adaptations to endurance exercise, may also regulate biological processes associated with short-term muscle unloading.
Highlights
Skeletal muscle has a high degree of plasticity, quickly adapting its structural and functional properties in response to disruption of homeostasis
The response to endurance training was significantly different between low responders to endurance training (LRT) and high responders to endurance training (HRT) (P
Myosin heavy chain (Myh) expression was examined to analyse muscle fibre phenotypes as well as validate RNA sequencing (RNAseq) workflow by examining Myh expression in well-characterized muscle fibre phenotypes
Summary
Skeletal muscle has a high degree of plasticity, quickly adapting its structural and functional properties in response to disruption of homeostasis. To account for heterogeneity and better understand genetic factors in the response to training, a selective breeding model has been developed that demonstrates improved running capacity and metabolic function in high responders to endurance training (HRT), compared with low responders to endurance training (LRT) that have reduced running capacity and impaired metabolism [4]. Chronic diseases such as cancer, diabetes and obesity, and the effects of aging leading to sarcopenia, are often accompanied by shared maladaptation responses in skeletal muscle [5]. Whether the response to exercise training is associated with the severity of immobilization-induced muscle atrophy is currently unknown
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