Department of Aerospace Physiology, Air Force Medical University, Xi'an, China.
Department of Nuclear Medicine, Xijing Hospital, Air Force Medical University, Xi'an, China.
Cell Death Dis. 2021 Nov 3;12(11):1045. doi: 10.1038/s41419-021-04351-x.
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.
快速适应低氧环境是一个悬而未决的问题，我们致力于对此进行探索。目前，尚无实现快速低氧适应的合适策略。在这里，我们证明禁食预处理 72 小时可减少组织损伤并维持心脏功能，从而显著提高大鼠在极端低氧环境下的存活率，并且该策略可用于快速低氧适应。在机制上，禁食可降低血糖并进一步抑制组织 mTOR 活性。一方面，禁食诱导的 mTOR 抑制作用可减少急性低氧下不必要的 ATP 消耗，并通过减少蛋白质合成和脂肪生成来增加 ATP 储备；另一方面，禁食诱导的 mTOR 抑制作用可提高线粒体的氧气利用效率，以确保在急性低氧下产生 ATP，这是由于增强的线粒体自噬作用导致 ROS 生成显著减少。我们的研究结果强调了 mTOR 在急性低氧适应中的重要作用，靶向调节 mTOR 可能是提高机体急性低氧耐受能力的新策略。
