Sending the signal: Muscle glycogen availability as a regulator of training adaptation

Exercise training-induced adaptations in human skeletal muscle are largely determined by the mode, volume, intensity and frequency of the training stimulus. However, a growing body of evidence demonstrates that the availability of endogenous and exogenous macronutrients can modify multiple intramuscular responses to both endurance- and resistance-based exercise. Acutely manipulating substrate availability (by altering diet composition and/or timing of meals) rapidly alters the concentration of blood-borne substrates and hormones that modulate several receptor-mediated signaling pathways. The release of cytokines and growth factors from contracting skeletal muscle also stimulates cell surface receptors and activates many intracellular signaling cascades. These local and systemic factors cause marked perturbations in the storage profile of skeletal muscle (and other insulin-sensitive tissues) that, in turn, exert pronounced effects on resting fuel metabolism and patterns of fuel utilization during exercise. When repeated over weeks and months, such nutrient-exercise interactions have the potential to alter numerous adaptive processes in skeletal muscle that ultimately drive the phenotype-specific variability observed between individuals. One strategy that augments endurance-training adaptation is commencing exercise with low muscle glycogen concentration (“train-low”). The amplified training response observed with low endogenous carbohydrate availability is likely regulated by enhanced activation of key cell signalling kinases (e.g., AMPK, p38MAPK), transcription factors (e.g., p53, PPARδ) and transcriptional co-activators (e.g., PGC-1α), such that a coordinated up-regulation of both the nuclear and mitochondrial genomes occurs. This chapter provides a contemporary perspective of our understanding of the molecular and cellular events that take place in skeletal muscle in response to exercise commenced after alterations in nutrient availability and discusses how the ensuing hormonal milieu interacts with specific contractile stimulus to modulate many of the acute responses to exercise, thereby potentially promoting or inhibiting subsequent training adaptation.