肌肉衍生的小细胞外囊泡在过度训练时诱导肝纤维化
Ya Liu1, Rui Zhou1, Yifan Guo1
1Department of Endocrinology, Endocrinology Research Center, Xiangya Hospital of Central South University, 410008 Changsha, Hunan, China.
Cell metabolism
|January 29, 2025
概括
过度训练会通过过度的乳酸积累引起肝纤维化,导致引发肝细胞死亡的"乳酸体". 针对这个过程,特别是SORBS3乳化或FBXO2,可以防止运动引起的肝损伤.
科学领域:
- 运动生理学 运动生理学
- 分子生物学分子生物学
- 肝病学 肝病学是一种肝病学.
背景情况:
- 运动以剂量依赖的方式提供代谢益处.
- 过度训练的不良影响及其机制尚不清楚.
- 肝纤维化是一个重大的健康问题.
研究的目的:
- 阐明过度训练引发肝纤维化的机制.
- 为了确定潜在的治疗目标,以减轻过度训练引起的肝损伤.
主要方法:
- 研究了乳酸积累的作用及其对骨肌肉的下游影响.
- 利用分子生物学技术研究蛋白质乳糖化,液态液相分离 (LLPS) 和细胞外囊泡形成.
- 在过度训练模型中,研究了抑制特定蛋白质 (SORBS3,FBXO2) 和药理干预 (salidroside) 对肝纤维化标志物的影响.
主要成果:
- 过度训练会导致骨肌肉中乳酸的过度积累,导致SORBS3的乳化,并触发其LLPS.
- 乳基化SORBS3促进"乳酸体" (含有FBXO2的细胞外囊泡) 的形成,从而诱导肝细胞亡和肝星细胞激活.
- 抑制SORBS3乳化或FBXO2,并通过salidroside减少肌肉乳酸体,减弱过度训练引起的肝纤维化.
结论:
- 过度训练通过涉及乳酸体的新途径诱导肝纤维化.
- 针对SORBS3乳化,FBXO2或乳酸体形成,为保护肝脏免受过度训练的压力提供了潜在的治疗策略.
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