Role of Pro-inflammatory Cytokines in Regulation of Skeletal Muscle Metabolism: A Systematic Review

Abstract

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.