Interleukin-13 drives metabolic conditioning of muscle to endurance exercise

Science. 2020 May 1;368(6490):eaat3987. doi: 10.1126/science.aat3987. Epub 2020 Apr 30.


Repeated bouts of exercise condition muscle mitochondria to meet increased energy demand-an adaptive response associated with improved metabolic fitness. We found that the type 2 cytokine interleukin-13 (IL-13) is induced in exercising muscle, where it orchestrates metabolic reprogramming that preserves glycogen in favor of fatty acid oxidation and mitochondrial respiration. Exercise training-mediated mitochondrial biogenesis, running endurance, and beneficial glycemic effects were lost in Il13-/- mice. By contrast, enhanced muscle IL-13 signaling was sufficient to increase running distance, glucose tolerance, and mitochondrial activity similar to the effects of exercise training. In muscle, IL-13 acts through both its receptor IL-13Rα1 and the transcription factor Stat3. The genetic ablation of either of these downstream effectors reduced running capacity in mice. Thus, coordinated immunological and physiological responses mediate exercise-elicited metabolic adaptations that maximize muscle fuel economy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptation, Physiological / immunology*
  • Animals
  • Blood Glucose / metabolism
  • Cell Line
  • Fatty Acids / metabolism
  • Female
  • Glycogen / metabolism*
  • Humans
  • Interleukin-13 / blood
  • Interleukin-13 / genetics
  • Interleukin-13 / metabolism*
  • Interleukin-13 Receptor alpha1 Subunit / genetics
  • Interleukin-13 Receptor alpha1 Subunit / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mitochondria, Muscle / metabolism*
  • Muscle, Skeletal / metabolism*
  • Myoblasts / metabolism
  • Oxidation-Reduction
  • Physical Conditioning, Animal
  • Physical Endurance / immunology*
  • Running
  • STAT3 Transcription Factor / genetics
  • STAT3 Transcription Factor / metabolism


  • Blood Glucose
  • Fatty Acids
  • Interleukin-13
  • Interleukin-13 Receptor alpha1 Subunit
  • STAT3 Transcription Factor
  • Stat3 protein, mouse
  • Glycogen