GLP-1 regulates exercise endurance and skeletal muscle remodeling via GLP-1R/AMPK pathway
GLP-1 regulates exercise endurance and skeletal muscle remodeling via GLP-1R/AMPK pathway
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GLP-1 通过 GLP-1R/AMPK 通路调节运动耐力和骨骼肌重塑
DOI：
10.1016/j.bbamcr.2022.119300
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Mantian Mi
中科院分区：
文献类型：
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作者：
Luting Wu;Min Zhou;Tianyou Li;Niu Dong;Long Yi;Qianyong Zhang;Mantian Mi
运动引起的身体耐力增强和骨骼肌重塑可以预防和延缓多种疾病的发展，特别是代谢综合征。在此，该研究探讨了胰高血糖素样肽-1 (GLP-1) 分泌与运动之间的关联，及其对骨骼肌重塑以增强耐力能力的影响。我们发现急性运动和短期耐力训练均显着增加小鼠 GLP-1 的分泌。编码Gcg（胰高血糖素原）的重组腺相关病毒（AAV）被用来诱导小鼠骨骼肌中GLP-1的过度表达。骨骼肌中 GLP-1 的过度表达增强了耐力。同时，GLP-1-AAV 骨骼肌中的糖原合成、葡萄糖摄取、I 型纤维比例和线粒体生物发生均得到增强。此外，体外实验表明exendin-4（一种GLP-1受体激动剂）治疗显着促进葡萄糖摄取、I型纤维形成和线粒体呼吸。从机制上讲，敲除 AMPK 可以逆转体外 GLP-1R 激活所带来的影响。综上所述，这些结果证实 GLP-1 可能通过 GLP-1R 信号介导的 AMPK 磷酸化来调节骨骼肌重塑以增强运动耐力。
Exercise-induced physical endurance enhancement and skeletal muscle remodeling can prevent and delay the development of multiple diseases, especially metabolic syndrome. Herein, the study explored the association between glucagon-like peptide-1 (GLP-1) secretion and exercise, and its effect on skeletal muscle remodeling to enhance endurance capacity. We found both acute exercise and short-term endurance training significantly increased the secretion of GLP-1 in mice. Recombinant adeno-associated virus (AAV) encoding Gcg (proglucagon) was used to induce the overexpression of GLP-1 in skeletal muscle of mice. Overexpression of GLP-1 in skeletal muscle enhanced endurance capacity. Meanwhile, glycogen synthesis, glucose uptake, type I fibers proportion, and mitochondrial biogenesis were augmented in GLP-1-AAV skeletal muscle. Furthermore, the in vitro experiment showed that exendin-4 (a GLP-1 receptor agonist) treatment remarkably promoted glucose uptake, type I fibers formation, and mitochondrial respiration. Mechanistically, the knockdown of AMPK could reverse the effects imposed by GLP-1R activation in vitro. Taken together, these results verify that GLP-1 regulates skeletal muscle remodeling to enhance exercise endurance possibly via GLP-1R signaling-mediated phosphorylation of AMPK.