Fasting promotes acute hypoxic adaptation by suppressing mTOR-mediated pathways

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 fun...

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Autores principales:	Ruzhou Zhao, Xingcheng Zhao, Xiaobo Wang, Yanqi Liu, Jie Yang, Shuai Jiang, Xiang Zhou, Bo Jiao, Lin Zhang, Yong Liu, Zhibin Yu
Formato:	article
Lenguaje:	EN
Publicado:	Nature Publishing Group 2021
Materias:	Cytology QH573-671
Acceso en línea:	https://doaj.org/article/d4dfc4e912dc4f32b7e6535ee773490a
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spelling	oai:doaj.org-article:d4dfc4e912dc4f32b7e6535ee773490a2021-11-07T12:05:34ZFasting promotes acute hypoxic adaptation by suppressing mTOR-mediated pathways10.1038/s41419-021-04351-x2041-4889https://doaj.org/article/d4dfc4e912dc4f32b7e6535ee773490a2021-11-01T00:00:00Zhttps://doi.org/10.1038/s41419-021-04351-xhttps://doaj.org/toc/2041-4889Abstract 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.Ruzhou ZhaoXingcheng ZhaoXiaobo WangYanqi LiuJie YangShuai JiangXiang ZhouBo JiaoLin ZhangYong LiuZhibin YuNature Publishing GrouparticleCytologyQH573-671ENCell Death and Disease, Vol 12, Iss 11, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Cytology QH573-671
spellingShingle	Cytology QH573-671 Ruzhou Zhao Xingcheng Zhao Xiaobo Wang Yanqi Liu Jie Yang Shuai Jiang Xiang Zhou Bo Jiao Lin Zhang Yong Liu Zhibin Yu Fasting promotes acute hypoxic adaptation by suppressing mTOR-mediated pathways
description	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.
format	article
author	Ruzhou Zhao Xingcheng Zhao Xiaobo Wang Yanqi Liu Jie Yang Shuai Jiang Xiang Zhou Bo Jiao Lin Zhang Yong Liu Zhibin Yu
author_facet	Ruzhou Zhao Xingcheng Zhao Xiaobo Wang Yanqi Liu Jie Yang Shuai Jiang Xiang Zhou Bo Jiao Lin Zhang Yong Liu Zhibin Yu
author_sort	Ruzhou Zhao
title	Fasting promotes acute hypoxic adaptation by suppressing mTOR-mediated pathways
title_short	Fasting promotes acute hypoxic adaptation by suppressing mTOR-mediated pathways
title_full	Fasting promotes acute hypoxic adaptation by suppressing mTOR-mediated pathways
title_fullStr	Fasting promotes acute hypoxic adaptation by suppressing mTOR-mediated pathways
title_full_unstemmed	Fasting promotes acute hypoxic adaptation by suppressing mTOR-mediated pathways
title_sort	fasting promotes acute hypoxic adaptation by suppressing mtor-mediated pathways
publisher	Nature Publishing Group
publishDate	2021
url	https://doaj.org/article/d4dfc4e912dc4f32b7e6535ee773490a
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_version_	1718443577956106240

Fasting promotes acute hypoxic adaptation by suppressing mTOR-mediated pathways

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