Role of GDF15 in active lifestyle induced metabolic adaptations and acute exercise response in mice
Role of GDF15 in active lifestyle induced metabolic adaptations and acute exercise response in mice
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DOI：
10.1038/s41598-019-56922-w
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发表时间：
2019-12-27
影响因子：
4.6
通讯作者：
Klaus, Susanne
中科院分区：
文献类型：
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作者：
Gil, Carla Igual;Ost, Mario;Klaus, Susanne
体力活动是肌肉适应和新陈代谢健康的重要因素。生长分化因子15(GDF15)是一种细胞和营养应激诱导的细胞因子，但其在积极生活方式或急性运动中的生理作用尚不清楚。在这里，我们研究了长期自愿车轮跑(VWR)干预的瘦小和肥胖雄性C57BI/6J小鼠的代谢表型和循环GDF15水平。此外，还检测了GDF15消融小鼠的跑步机跑步能力和运动诱导的肌肉基因表达。通过VWR模拟积极的生活方式改善了跑步机跑步性能，在肥胖小鼠中也改善了代谢表型。VWR降低了运动后骨骼肌转录应激标志物的诱导。骨骼肌GDF15基因的表达非常低，仅在久坐运动后短暂增加，而在活跃的小鼠中则不表达。慢性或急性运动对血浆GDF15水平的影响很小。在肥胖小鼠中，VWR降低了不同组织中GDF15基因的表达，但不能逆转血浆GDF15的升高。基因消融GDF15对运动成绩没有影响，但增加了运动后骨骼肌转录应激标志物(ATF3、ATF6和Xbp1s)的表达。我们的结论是，骨骼肌对小鼠的循环GDF15没有贡献，但肌肉GDF15可能在运动应激反应中起到保护作用。
Physical activity is an important contributor to muscle adaptation and metabolic health. Growth differentiation factor 15 (GDF15) is established as cellular and nutritional stress-induced cytokine but its physiological role in response to active lifestyle or acute exercise is unknown. Here, we investigated the metabolic phenotype and circulating GDF15 levels in lean and obese male C57BI/6J mice with long-term voluntary wheel running (VWR) intervention. Additionally, treadmill running capacity and exercise-induced muscle gene expression was examined in GDF15-ablated mice. Active lifestyle mimic via VWR improved treadmill running performance and, in obese mice, also metabolic phenotype. The post-exercise induction of skeletal muscle transcriptional stress markers was reduced by VWR. Skeletal muscle GDF15 gene expression was very low and only transiently increased post-exercise in sedentary but not in active mice. Plasma GDF15 levels were only marginally affected by chronic or acute exercise. In obese mice, VWR reduced GDF15 gene expression in different tissues but did not reverse elevated plasma GDF15. Genetic ablation of GDF15 had no effect on exercise performance but augmented the post exercise expression of transcriptional exercise stress markers (Atf3, Atf6, and Xbp1s) in skeletal muscle. We conclude that skeletal muscle does not contribute to circulating GDF15 in mice, but muscle GDF15 might play a protective role in the exercise stress response.