Interleukin-13 drives metabolic conditioning of muscle to endurance exercise

IL-13 hits the gym Interleukin-13 (IL-13) is a cytokine secreted by T cells, innate lymphoid cells (ILC2s), and granulocytes. It acts as a central mediator in allergy and antihelminth defense with various effects. Knudsen et al. report a distinct role for IL-13 in exercise and metabolism (see the Perspective by Correia and Ruas). Mice subjected to endurance training showed increases in circulating IL-13, which correlated with ILC2 expansion in the muscles. By contrast, exercise-induced increases in muscle fatty acid utilization and mitochondrial biogenesis were erased when mice lacked IL-13. Activation of signaling pathways downstream of the muscle IL-13 receptor was key to this effect. Intramuscular injection of adenoviral IL-13 could recapitulate exercise-induced metabolic reprogramming. This signaling pathway may have evolved to combat the metabolic stresses of parasite infection. Science , this issue p. eaat3987 ; see also p. 470