Background:
Metabolic pathways perturbations lead to skeletal muscular atrophy in the
cachexia and sarcopenia due to increased catabolism. Pro-inflammatory cytokines induce the catabolic
pathways that impair the muscle integrity and function. Hence, this review primarily concentrates
on the effects of pro-inflammatory cytokines in regulation of skeletal muscle metabolism.
Objective:
This review will discuss the role of pro-inflammatory cytokines in skeletal muscles during
muscle wasting conditions. Moreover, the coordination among the pro-inflammatory cytokines
and their regulated molecular signaling pathways which increase the protein degradation will be
discussed.
Results:
During normal conditions, pro-inflammatory cytokines are required to balance anabolism
and catabolism and to maintain normal myogenesis process. However, during muscle wasting their
enhanced expression leads to marked destructive metabolism in the skeletal muscles. Proinflammatory
cytokines primarily exert their effects by increasing the expression of calpains and E3
ligases as well as of Nf-κB, required for protein breakdown and local inflammation. Proinflammatory
cytokines also locally suppress the IGF-1and insulin functions, hence increase the
FoxO activation and decrease the Akt function, the central point of carbohydrates lipid and protein
metabolism.
Conclusion:
Current advancements have revealed that the muscle mass loss during skeletal muscular
atrophy is multifactorial. Despite great efforts, not even a single FDA approved drug is available
in the market. It indicates the well-organized coordination among the pro-inflammatory cytokines
that need to be further understood and explored.