Equine skeletal muscle adaptations to exercise and training: evidence of differential regulation of autophagosomal and mitochondrial components

Abstract

BackgroundA single bout of exercise induces changes in gene expression in skeletal muscle. Regular exercise results in an adaptive response involving changes in muscle architecture and biochemistry, and is an effective way to manage and prevent common human diseases such as obesity, cardiovascular disorders and type II diabetes. However, the biomolecular mechanisms underlying such responses still need to be fully elucidated. Here we performed a transcriptome-wide analysis of skeletal muscle tissue in a large cohort of untrained Thoroughbred horses (n = 51) before and after a bout of high-intensity exercise and again after an extended period of training. We hypothesized that regular high-intensity exercise training primes the transcriptome for the demands of high-intensity exercise.ResultsAn extensive set of genes was observed to be significantly differentially regulated in response to a single bout of high-intensity exercise in the untrained cohort (3241 genes) and following multiple bouts of high-intensity exercise training over a six-month period (3405 genes). Approximately one-third of these genes (1025) and several biological processes related to energy metabolism were common to both the exercise and training responses. We then developed a novel network-based computational analysis pipeline to test the hypothesis that these transcriptional changes also influence the contextual molecular interactome and its dynamics in response to exercise and training. The contextual network analysis identified several important hub genes, including the autophagosomal-related gene GABARAPL1, and dynamic functional modules, including those enriched for mitochondrial respiratory chain complexes I and V, that were differentially regulated and had their putative interactions ‘re-wired’ in the exercise and/or training responses.ConclusionHere we have generated for the first time, a comprehensive set of genes that are differentially expressed in Thoroughbred skeletal muscle in response to both exercise and training. These data indicate that consecutive bouts of high-intensity exercise result in a priming of the skeletal muscle transcriptome for the demands of the next exercise bout. Furthermore, this may also lead to an extensive ‘re-wiring’ of the molecular interactome in both exercise and training and include key genes and functional modules related to autophagy and the mitochondrion.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-017-4007-9) contains supplementary material, which is available to authorized users.

Identification of expression quantitative trait loci in the skeletal muscle of Thoroughbreds reveals heritable variation in expression of genes relevant to cofactor metabolism

“…The total set of genes with expression changes associated with eQTLs (i.e. eGenes) were queried against genes that we have reported from the same dataset to be differentially expressed post-exercise (Bryan et al, 2017). Of the 3,582 UR cis -eQTL, 913 were associated with genes differentially expressed in response to exercise.…”

“…Using 3,405 genes that were differentially expressed in response to training (Bryan et al, 2017), we examined our results based on eQTL associated with genes within this transcriptional response. Within the UR cohort, 609 of the 3,582 cis -eQTL were associated with training response genes.…”

“…eQTL located within 1 Mb of the transcription start site (TSS) of the gene they were associated were designated as cis , and those located >1Mb from the TSS were designated trans . Significant results were then compared against genes previously identified in the skeletal muscle transcriptional response to acute, high-intensity exercise (a work day; 3,241 genes) and transcriptional response to a six-month period of training (3,405 genes) (Bryan et al, 2017).…”

Genomic inbreeding trends in the global Thoroughbred horse population driven by influential sire lines and selection for exercise trait-related genes

“…An emerging theme in equine transcriptomics and genomics research suggests a link between the exercise phenotype and behavioural plasticity. For example, in the skeletal muscle transcriptome response to exercise training, neurological processes were the most significantly over-represented gene ontology (GO) terms, with the top three ranked GO terms being Neurological system process ( P = 4.85 × 10 −27 ), Cognition ( P = 1.92 × 10 −22 ) and Sensory perception ( P = 4.21 × 10 −21 ) [66]. Furthermore, in genome-wide association (GWA) studies genes involved in behavioural plasticity are the most strongly associated with economically important traits in racing Thoroughbreds: precocity (early adaptation to racing) [67] and the likelihood of racing [19].…”

A genomic prediction model for racecourse starts in the Thoroughbred horse

“…In a recent transcriptomics study, using RNA‐seq in equine skeletal muscle, the NTM gene was not differentially expressed in response to exercise or training whereas OPCML transcripts were significantly differentially expressed following a period of training (0.447 fold, P = 0.0074; Table ; Bryan et al . ). Although the functional effects of NTM and OPCML in the horse are not fully understood, these results suggest that these genes could play a role in physiological or behavioural adaptations required for early racing and training.…”