Interleukin-13 drives metabolic conditioning of muscle to endurance exercise.

Interleukin-13 drives metabolic conditioning of muscle to endurance exercise.
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DOI:
10.1126/science.aat3987
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发表时间:
2020-05-01
期刊:
Science (New York, N.Y.)
影响因子:
--
通讯作者:
Lee CH
Lee CH
中科院分区:
其他
文献类型:
--
作者:
Knudsen NH;Stanya KJ;Hyde AL;Chalom MM;Alexander RK;Liou YH;Starost KA;Gangl MR;Jacobi D;Liu S;Sopariwala DH;Fonseca-Pereira D;Li J;Hu FB;Garrett WS;Narkar VA;Ortlund EA;Kim JH;Paton CM;Cooper JA;Lee CH

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反复的运动会使肌肉线粒体适应增加的能量需求,这是一种与改善代谢适应性相关的适应性反应。我们发现,2型细胞因子白细胞介素-13(IL-13)在运动肌肉中被诱导,在那里它协调代谢重编程,保护糖原,有利于脂肪酸氧化和线粒体呼吸。运动训练介导的线粒体生物合成,跑步耐力和有益的血糖效应在Il 13 −/−小鼠中丢失。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,与运动训练相似。IL-13通过肌肉IL-13 R α1和Stat 3发挥作用。这些下游效应子中的任何一个的基因切除都会降低跑步能力。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。耐力运动激活IL-13信号传导以调节肌肉线粒体氧化能力和葡萄糖稳态。
Repeated bouts of exercise condition muscle mitochondria to meet increased energy demand, an adaptive response associated with improved metabolic fitness. We find 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 are lost in Il13−/− mice. By contrast, enhanced muscle IL-13 signaling is sufficient to increase running distance, glucose tolerance, and mitochondrial activity similar to that of exercise training. IL-13 acts through both muscle IL-13Rα1 and Stat3. The genetic ablation of either of these downstream effectors reduces running capacity. Thus, coordinated immunological and physiological responses mediate exercise-elicited metabolic adaptations that maximize muscle fuel economy. Endurance exercise activates IL-13 signaling to regulate muscle mitochondrial oxidative capacity and glucose homeostasis.
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