Molecular responses to acute exercise and their relevance for adaptations in skeletal muscle to exercise training

Abstract

Repeated, episodic bouts of skeletal muscle contraction undertaken frequently as structured exercise training is a potent stimulus for physiological adaptation in many organs. Specifically in skeletal muscle, remarkable plasticity is demonstrated by the remodeling of muscle structure and function in terms of muscular size, force, endurance, and contractile velocity as a result of the functional demands induced by various types of exercise training. This plasticity, and the mechanistic basis for adaptations to skeletal muscle in response to exercise training, is underpinned by activation and/or repression of molecular pathways and processes induced in response to each individual acute exercise session. These pathways include the transduction of signals arising from neuronal, mechanical, metabolic, and hormonal stimuli through complex signal transduction networks, which are linked to a myriad of effector proteins involved in the regulation of pre- and post-transcriptional processes, and protein translation and degradation processes. This review therefore describes acute exercise-induced signal transduction and the molecular responses to acute exercise in skeletal muscle including emerging concepts such as epigenetic pre- and post-transcriptional regulation, and the regulation of protein translation and degradation. A critical appraisal of methodological approaches and the current state of knowledge informs a series of recommendations offered as future directions in the field.

Molecular control of endurance training adaptation in mouse skeletal muscle

“…Accordingly, almost half of all upregulated genes in trained muscle peak at 0h while this only applies to ~20% of the upregulated genes in untrained muscle (majority peaks after 6h) (Figure 3D). Overall, opposed to the model of general attenuation of gene expression with training habituation 3,10,11,[13][14][15] , our results suggest a much more complex picture, with significant occurrence of all scenarios: attenuation, exacerbation, and selective expression changes in the naïve or trained muscle after an acute exercise bout (Figure 3E). Moreover, most of the acute transcriptional changes are not retained in an unperturbed trained muscle (Figure S4D).…”

“…Skeletal muscle exerts pleiotropic functions, from thermoregulation through shivering, to endocrine signaling by myokines and myometabolites, and detoxification of endogenous compounds, e.g. kynurenines or aberrantly high levels of ketone bodies [1][2][3][4][5] . However, the main task of skeletal muscle is the generation of force for different types of contractile activities, including strength, endurance, fine motor control, posture or breathing.…”

“…Skeletal muscle thus not only exhibits broad morphological and functional specification, but also a remarkable adaptive plasticity to react to internal and external perturbations 4 . Remodeling of skeletal muscle requires interventions that disrupt homeostasis, to which muscle will progressively adapt only if repeated over time 3,4 . Morphologically, such adaptations are well described, e.g.…”

“…In light of the powerful health benefits conferred by either modality of exercise 6,7 , it however is surprising that the molecular underpinnings of muscle plasticity in exercise are still only rudimentarily understood 4 . In particular, the mechanistic framework that links the perturbations evoked by individual, acute exercise bouts to long-term training adaptations are largely unknown 3,4 . Additionally, it is unclear how the training status affects the molecular response to an acute bout of exercise, and how changes in gene expression are ultimately linked to persistent modulation of protein levels, organelle function and tissue plasticity.…”

Human skeletal muscle methylome after low carbohydrate energy balanced exercise

“…Previous studies have also identified that DNA methylation changes are extensive even at 30 minutes post exercise after resistance exercise (14) and also more extensive at 3 hr compared with later 6 hr timepoints ( 16) and also at 30 minutes compared with 24 hr time points after high intensity sprint interval exercise (15). Such early alterations in DNA methylation occur rapidly after exercise, and due to the known mechanistic role methylation has in altering accessibility and binding of transcription factors necessary for transcription, continues to supports the notion that DNA methylation precedes alterations in gene expression in the post exercise period, where gene expression typically peaks at around 3-6 hours post-exercise (39). The predominance of promoter hypomethylation at 30 minutes in low-CHO energy balance compared with energy deficit conditions was enriched in KEGG pathway: 'viral carcinogensis', that includes relevant exercise and SkM genes/pathways such as IL6-JAK-STAT signalling and p53 / cell cycle pathways.…”