English: "The majority of exercise mimetics have targeted metabolic networks within skeletal muscle (left panel). The discovery of muscle ‘cross-talk’ with multiple organs including adipose tissue, liver, pancreas, bone and the brain (right panel), has provided exercise biologists with a mechanistic framework for understanding how exercise mediates many of its beneficial whole-body effects on health. While some myokines exert their actions on other organs in an endocrine fashion, others operate locally on skeletal muscle and thereby provide a feedback loop for the muscle to regulate its own growth and regeneration for adaptation to exercise training. In addition, muscle energy status (i.e. glycogen) exerts profound effects on acute regulatory processes underlying gene expression and cell signalling. As such, nutrient–exercise interactions have the potential to upregulate many biochemical pathways with putative roles in training adaptation. It is highly unlikely that any exercise pill/mimetic or combinations thereof could ever replicate the widespread effects of exercise on other organs/tissues, or respond to changes in the prevailing muscle fuel stores."