PPARδ Promotes Running Endurance by Preserving Glucose.
PPARδ Promotes Running Endurance by Preserving Glucose.
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DOI：
10.1016/j.cmet.2017.04.006
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发表时间：
2017-05-02
期刊：
影响因子：
29
通讯作者：
Evans RM
中科院分区：
文献类型：
--
作者：
Fan W;Waizenegger W;Lin CS;Sorrentino V;He MX;Wall CE;Li H;Liddle C;Yu RT;Atkins AR;Auwerx J;Downes M;Evans RM
在耐力训练中，能量储备的管理是至关重要的，底物利用从葡萄糖转向脂肪是训练肌肉的标志。在这里，我们表明这一关键的代谢适应既依赖于肌肉PPARδ，也受到PPARδ配体的刺激。此外，我们发现在BXD小鼠参考种群中，肌肉PPARδ的表达与耐力表现呈正相关。除了刺激久坐不动的小鼠的脂肪酸代谢外，PPARδ的激活还能有效地抑制葡萄糖的分解代谢，而且不会影响肌肉纤维类型或线粒体含量。通过保持全身血糖水平，PPARδ可延缓低血糖的发生，并在接受治疗的小鼠中延长运行时间约100分钟。总而言之，这些结果确定了一项以节省葡萄糖为基础的PPARδ计划，并突出了PPARδ靶向运动模拟在治疗代谢性疾病、营养不良以及不可避免地提高运动成绩方面的潜力。耐力运动中的碳水化合物消耗会导致“碰壁”现象，通过运动训练可以缓解这种现象。XXX等人的研究表明，肌肉PPARδ能有效抑制葡萄糖分解代谢。在接受激动剂治疗的小鼠中，PPARδ节省葡萄糖可以延缓低血糖的发生，并将运行时间延长约100分钟。
Management of energy stores is critical during endurance exercise, with a shift in substrate utilization from glucose towards fat being a hallmark of trained muscle. Here we show that this key metabolic adaptation is both dependent on muscle PPARδ and stimulated by PPARδ ligand. Furthermore, we find that muscle PPARδ expression positively correlates with endurance performance in BXD mouse reference populations. In addition to stimulating fatty acid metabolism in sedentary mice, PPARδ activation potently suppresses glucose catabolism and does so without affecting either muscle fiber type or mitochondrial content. By preserving systemic glucose levels PPARδ acts to delay the onset of hypoglycemia and extends running time by ~100 minutes in treated mice. Collectively, these results identify a bifurcated PPARδ program that underlies glucose sparing and highlight the potential of PPARδ-targeted exercise mimetics in the treatment of metabolic disease, dystrophies and unavoidably, the enhancement of athletic performance. Carbohydrate depletion in endurance sports leads to “hitting the wall” phenomenon, which is mitigated through sports training. XXX et al show that muscle PPARδ actively suppresses glucose catabolism. Glucose sparing by PPARδ delays the onset of hypoglycemia and extends running time by ~100 minutes in agonist-treated mice.