2. Academic Validation
  3. Adaptive metabolic response to short-term intensive fasting

Adaptive metabolic response to short-term intensive fasting

  • Clin Nutr. 2023 Dec 30;43(2):453-467. doi: 10.1016/j.clnu.2023.12.020.
Suping Zhang 1,  Yaqi Lv 2,  Jiawei Qian 2,  Wen Wei 3,  Yanfei Zhu 2,  Yuqing Liu 2,  Lei Li 3,  Chen Zhao 3,  Xueqin Gao 2,  Yanjun Yang 4,  Jin Dong 2,  Yue Gu 2,  Yuwei Chen 4,  Qiyuan Sun 4,  Xuehua Jiao 4,  Jie Lu 4,  Zhanjun Yan 4,  Li Wang 5,  Na Yuan 6,  Yixuan Fang 7,  Jianrong Wang 8
Affiliations

Affiliations

  • 1 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.
  • 2 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.
  • 3 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; Susky Life SciTech (Suzhou) Inc., Suzhou 215101, China.
  • 4 Suzhou Ninth Hospital Affiliated to Soochow University, Suzhou 215200, China.
  • 5 Department of Community Nursing, School of Nursing, Soochow University, Suzhou 215006, China.
  • 6 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; Susky Life SciTech (Suzhou) Inc., Suzhou 215101, China. Electronic address: nyuan@suda.edu.cn.
  • 7 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; Susky Life SciTech (Suzhou) Inc., Suzhou 215101, China. Electronic address: yxfang@suda.edu.cn.
  • 8 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; Susky Life SciTech (Suzhou) Inc., Suzhou 215101, China; Suzhou Ninth Hospital Affiliated to Soochow University, Suzhou 215200, China. Electronic address: jrwang@suda.edu.cn.
PMID: 38181523 DOI: 10.1016/j.clnu.2023.12.020
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.

Keywords

Adaptive response; Beego; Catabolic enzymes; Kidney; Liver; Metabolite accumulation; Short-term intensive fasting.

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