在运动中调节肌肉AMPK激活
Yang Liu1,2, Phong T Nguyen3,4, Xun Wang5,6
1Center for Autophagy Research, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA. yang.liu3@utsouthwestern.edu.
Nature
|February 14, 2020
概括
托尔类受体9 (TLR9) 在运动诱导的氨酸单酸激活蛋白激酶 (AMPK) 激活中发挥关键作用. 这种先天免疫传感器与贝克林1相互作用,调节体力活动期间的葡萄糖代谢.
科学领域:
- 细胞生物学
- 免疫学
- 代谢过程
背景情况:
- 骨肌中的腺单激活蛋白激酶 (AMPK) 激活对于运动期间的全身代谢调节至关重要.
- 在运动期间,细胞平衡途径自被上调,贝克林1对AMPK激活至关重要.
- 托尔类受体9 (TLR9) 是一种先天性免疫传感器,在运动生理学中起到以前未知的作用.
研究的目的:
- 研究托尔类受体9 (TLR9) 在运动诱导的腺单酸激活蛋白激酶 (AMPK) 激活中的作用.
- 在运动和代谢压力背景下阐明TLR9和贝克林1之间的相互作用.
- 了解TLR9在体力活动期间对骨肌肉的葡萄糖运输和新陈代谢的贡献.
主要方法:
- 使用缺乏TLR9的淘汰小鼠来评估运动诱导的AMPK激活和GLUT4转运器定位.
- 在能量压力和BCL2突变条件下研究了TLR9和贝克林1之间的结合相互作用.
- 检查了TLR9在运动期间对内溶体酸丁醇3-激酶复合体 (PI3KC3-C2) 的调节作用.
- 在肌肉组织上进行了ex vivo实验,以评估收缩诱导的AMPK激活,葡萄糖吸收和复合组合.
主要成果:
- 缺少TLR9的小鼠表现出运动诱导的AMPK激活和骨肌中的GLUT4等离子膜定位受损.
- 发现TLR9与贝克林1结合,这种相互作用由能量压力和BCL2状态调节.
- 在运动期间,TLR9调节了骨肌肉中的PI3KC3- C2复合体组合;贝克林1或UVRAG敲击抑制了AMPK激活.
- TLR9在调解收缩诱导的AMPK激活,葡萄糖吸收和贝克林1-UVRAG复合物的过程中表现出肌肉自主功能.
结论:
- 托尔类受体9 (TLR9) 是骨肌腺单酸激活蛋白激酶 (AMPK) 激活和运动期间葡萄糖代谢的新型调节剂.
- 对于运动诱导的代谢适应,TLR9与贝克林1的相互作用及其在PI3KC3- C2复合体组合中的作用至关重要.
- 这些发现揭示了天生的免疫传感途径与骨肌肉中细胞能量调节之间的意想不到联系.
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