Department of Molecular Metabolism, Harvard T. H. Chan School of Public Health, Boston, MA 02115, USA.
Metabolic and Degenerative Diseases, Institute of Molecular Medicine, University of Texas McGovern Medical School, Houston, TX 77030, USA.
Science. 2020 May 1;368(6490). 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 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.
反复的运动锻炼会使肌肉线粒体适应能量需求的增加——这种适应性反应与代谢健康的改善有关。我们发现，细胞因子白细胞介素-13（IL-13）在运动肌肉中被诱导产生，它协调代谢重编程，以维持糖原，有利于脂肪酸氧化和线粒体呼吸。在 缺乏运动的小鼠中，运动训练介导的线粒体生物发生、跑步耐力和有益的血糖效应丧失。相比之下，增强的肌肉 IL-13 信号足以增加跑步距离、葡萄糖耐量和线粒体活性，类似于运动训练的效果。在肌肉中，IL-13 通过其受体 IL-13Rα1 和转录因子 Stat3 发挥作用。这些下游效应物中的任何一种的遗传缺失都会降低小鼠的跑步能力。因此，协调的免疫和生理反应介导运动引起的代谢适应，最大限度地提高肌肉燃料经济性。
