短期强化禁食的适应性代谢反应。

Adaptive metabolic response to short-term intensive fasting.

机构信息

Research Center for Blood Engineering and Manufacturing, Cyrus Tang Medical Institute, National Clinical Research Center for Hematologic Diseases, Collaborative Innovation Center of Hematology, Jiangsu Institute of Hematology, State Key Laboratory of Radiation Medicine and Protection, Soochow University, Suzhou 215123, China; Suzhou Center for Disease Control and Prevention, Suzhou 215004, China.

出版信息

Clin Nutr. 2024 Feb;43(2):453-467. doi: 10.1016/j.clnu.2023.12.020. Epub 2023 Dec 30.

DOI:10.1016/j.clnu.2023.12.020

PMID:38181523

Abstract

BACKGROUND & AIMS: Short-term intensive fasting (STIF), known as beego in Chinese phonetic articulation, has been practiced for more than two thousand years. However, the potential risk of STIF and the body's response to the risk have not been adequately evaluated. This study aims to address this issue, focusing on the STIF-triggered metabolic response of the liver and kidney.

METHODS

The STIF procedure in the clinical trial includes a 7-day water-only intensive fasting phase and a 7-day gradual refeeding phase followed by a regular diet. The intensive fasting in humans was assisted with psychological induction. To gain insights not available in the clinical trial, we designed a STIF program for mice that resulted in similar phenotypes seen in humans. Plasma metabolic profiling and examination of gene expression as well as liver and kidney function were performed by omics, molecular, biochemical and flow cytometric analyses. A human cell line model was also used for mechanistic study.

RESULTS

Clinically significant metabolites of fat and protein were found to accumulate during the fasting phase, but they were relieved after gradual refeeding. Metabolomics profiling revealed a universal pattern in the consumption of metabolic intermediates, in which pyruvate and succinate are the two key metabolites during STIF. In the STIF mouse model, the accumulation of metabolites was mostly counteracted by the upregulation of catabolic enzymes in the liver, which was validated in a human cell model. Kidney filtration function was partially affected by STIF but could be recovered by refeeding. STIF also reduced oxidative and inflammatory levels in the liver and kidney. Moreover, STIF improved lipid metabolism in mice with fatty liver without causing accumulation of metabolites after STIF.

CONCLUSIONS

The accumulation of metabolites induced by STIF can be relieved by spontaneous upregulation of catabolic enzymes, suggesting an adaptive and protective metabolic response to STIF stress in the mammalian body.

摘要

背景与目的

短期强化禁食（STIF），中文音译为“辟谷”，已有两千多年的历史。然而，STIF 的潜在风险及其对机体的影响尚未得到充分评估。本研究旨在探讨这一问题，重点关注 STIF 引发的肝肾功能代谢反应。

方法

临床试验中的 STIF 方案包括 7 天的纯水强化禁食期和 7 天的逐渐恢复进食期，随后恢复正常饮食。人类强化禁食期辅以心理诱导。为了深入了解临床试验中未涉及的内容，我们为小鼠设计了一种 STIF 方案，使小鼠出现了类似于人类的表型。通过组学、分子、生化和流式细胞术分析，对血浆代谢组学分析、基因表达以及肝肾功能进行检测。还使用人源细胞系模型进行了机制研究。

结果

临床研究发现，在禁食期间，脂肪和蛋白质的代谢产物明显积累，但在逐渐恢复进食后得到缓解。代谢组学分析揭示了一种普遍的代谢中间产物消耗模式，其中丙酮酸和琥珀酸是 STIF 期间的两个关键代谢物。在 STIF 小鼠模型中，肝脏中分解代谢酶的上调抵消了代谢物的积累，这一结果在人源细胞模型中得到了验证。STIF 对肾脏滤过功能有一定影响，但恢复进食后可恢复。STIF 还降低了肝、肾的氧化应激和炎症水平。此外，STIF 改善了脂肪肝小鼠的脂质代谢，且 STIF 后代谢物无积累。