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- Title
Fasting promotes acute hypoxic adaptation by suppressing mTOR-mediated pathways.
- Authors
Zhao, Ruzhou; Zhao, Xingcheng; Wang, Xiaobo; Liu, Yanqi; Yang, Jie; Jiang, Shuai; Zhou, Xiang; Jiao, Bo; Zhang, Lin; Liu, Yong; Yu, Zhibin
- Abstract
Rapid adaptation to a hypoxic environment is an unanswered question that we are committed to exploring. At present, there is no suitable strategy to achieve rapid hypoxic adaptation. Here, we demonstrate that fasting preconditioning for 72 h reduces tissue injuries and maintains cardiac function, consequently significantly improving the survival rates of rats under extreme hypoxia, and this strategy can be used for rapid hypoxic adaptation. Mechanistically, fasting reduces blood glucose and further suppresses tissue mTOR activity. On the one hand, fasting-induced mTOR inhibition reduces unnecessary ATP consumption and increases ATP reserves under acute hypoxia as a result of decreased protein synthesis and lipogenesis; on the other hand, fasting-induced mTOR inhibition improves mitochondrial oxygen utilization efficiency to ensure ATP production under acute hypoxia, which is due to the significant decrease in ROS generation induced by enhanced mitophagy. Our findings highlight the important role of mTOR in acute hypoxic adaptation, and targeted regulation of mTOR could be a new strategy to improve acute hypoxic tolerance in the body.
- Publication
Cell Death & Disease, 2021, Vol 12, Issue 11, p1
- ISSN
2041-4889
- Publication type
Article
- DOI
10.1038/s41419-021-04351-x