Disuse-associated atrophy has been attributed to fundamental molecular mechanisms such as decreased protein synthesis, increased protein degradation, suppression of bioenergetics pathways associated with mitochondrial function, and increased oxidative stress (Jankala et al., 1997; Kandarian and Jackman, 2006). Disuse-induced muscle atrophy is a highly ordered process that is controlled by interactions between intracellular signalling pathways.
Over the last five to ten years, the role of local hormones, growth factors and cytokines, produced by adipose tissue (adipokines) and skeletal muscle (myokines) have gained significant attention in the (patho)physiology of skeletal muscle behaviour. Although the roles of e.g., the insulin-like growth factors in muscle hypertrophy have been extensively debated, despite the early body of literature (Reid and Li, 2001; Hopkins, 1996; Wilcox et al., 1996; Wilcox et al., 1992; Wilcox et al., 1994), indicating that locally produced cytokines are involved in the regulation of skeletal muscle function in a fibre type specific manner (Plomgaard et al., 2005), controversy relating to benefits vs. detriments of cytokines in skeletal muscle remain to be more clearly defined. Indeed, the fibre type changes seen within disuse models could, therefore, perhaps be partially explained through changes in circulating cytokines.
This theorem is supported through unilateral limb suspension interventions inducing decreased myofibrillar, metabolic (glycolytic and oxidative) and antioxidant defense system proteins content (Brocca et al., 2015).