Muscle-immune metabolic crosstalk: shared pathways in cachexia and exercise

Skeletal muscle and the immune system continuously exchange metabolites and signals that are essential for homeostasis. Disruption of this communication, such as during infection, inflammation, or cancer, triggers cachexia, a severe wasting syndrome characterized by altered amino acid flux, mitochondrial dysfunction, and systemic energy imbalance. By contrast, regular exercise activates overlapping pathways but directs them toward regeneration and hypertrophy, supported by controlled cytokine release and metabolite exchange. This review outlines the metabolic reprogramming that underlies muscle-immune crosstalk in cachexia and exercise, emphasizing how identical mediators, including interleukin-6, can promote either catabolism or adaptation depending on context. Understanding these shared yet divergent pathways opens avenues for therapeutic strategies that target metabolism and immune-metabolic communication.