Interleukin-13 drives metabolic conditioning of muscle to endurance exercise
- 30 April 2020
- journal article
- research article
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 368 (6490), 488-+
- https://doi.org/10.1126/science.aat3987
Abstract
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.Keywords
Funding Information
- National Institutes of Health (F31DK107256)
- National Institutes of Health (F31GM117854)
- National Institutes of Health (R01DK113791)
- National Institutes of Health (R21AI131659)
- American Heart Association (16GRNT31460005)
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