Exercise-evoked immunometabolic niches coordinate context-dependent muscle metabolism

Exercise improves metabolic health; yet paradoxically, many exercise-responsive myokines and immune mediators are also implicated in chronic inflammation and metabolic dysfunction. In this opinion article, we propose that these immune responses are organized within spatially defined immunometabolic niches. Endothelial-associated neutrophils act as early coordinating cells that integrate muscle-derived and vascular signals, initiate local immune remodeling, and are associated with neutrophil extracellular trap formation. Metabolic outcomes arise from coordinated intercellular interactions rather than individual mediators, even in the absence of overt muscle injury. We further suggest that postexercise insulin sensitization emerges as a spatially regulated property of these niches. This perspective provides a conceptual framework in which inflammatory signals, including interleukin-1, exert context-dependent beneficial effects on metabolism and muscle function.