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ORIGINAL RESEARCH article

Front. Mol. Neurosci.
Sec. Molecular Signalling and Pathways
Volume 17 - 2024 | doi: 10.3389/fnmol.2024.1466125
This article is part of the Research Topic G Protein-Coupled Receptors in the Control of Energy Homeostasis and Food Intake View all articles

Every-other-day fasting inhibits pyroptosis while regulating bile acid metabolism and activating TGR5 signaling in spinal cord injury

Provisionally accepted
Honghu Song Honghu Song 1,2Rizhao Pang Rizhao Pang 2Zhixuan Chen Zhixuan Chen 1*Linjie Wang Linjie Wang 2Xiaomin Hu Xiaomin Hu 2*Jingzhi Feng Jingzhi Feng 1,2*Wenchun Wang Wenchun Wang 2Jiancheng Liu Jiancheng Liu 2*Anren Zhang Anren Zhang 3*
  • 1 Chengdu University of Traditional Chinese Medicine, Chengdu, China
  • 2 Western Theater General Hospital, Chengdu, Sichuan Province, China
  • 3 Shanghai Fourth People's Hospital, Shanghai, China

The final, formatted version of the article will be published soon.

    Every-other-day fasting (EODF) is a form of caloric restriction that alternates between periods of normal eating and fasting, aimed at preventing and treating diseases. This approach has gained widespread usage in basic research on neurological conditions, including spinal cord injury, and has demonstrated significant neuroprotective effects. Additionally, EODF is noted for its safety and feasibility, suggesting broad potential for application. This study aims to evaluate the therapeutic effects of EODF on spinal cord injury and to investigate and enhance its underlying mechanisms. Initially, the SCI rat model was utilized to evaluate the effects of EODF on pathological injury and motor function. Subsequently, considering the enhancement of metabolism through EODF, bile acid metabolism in SCI rats was analyzed using liquid chromatography-mass spectrometry (LC-MS), and the expression of the bile acid receptor TGR5 was further assessed. Ultimately, it was confirmed that EODF influences the activation of microglia and NLRP3 inflammasomes associated with the TGR5 signaling, along with the expression of downstream pyroptosis pathway related proteins and inflammatory cytokines, as evidenced by the activation of the NLRP3/Caspase-1/GSDMD pyroptosis pathway in SCI rats. The results demonstrated that EODF significantly enhanced the recovery of motor function and reduced pathological damage in SCI rats while controlling weight gain. Notably, EODF promoted the secretion of bile acid metabolites, activated TGR5, and inhibited the NLRP3/Caspase-1/GSDMD pyroptosis pathway and inflammation in these rats. In summary, EODF could mitigate secondary injury after SCI and foster functional recovery by improving metabolism, activating the TGR5 signaling and inhibiting the NLRP3 pyroptosis pathway.

    Keywords: every-other-day fasting, spinal cord injury, trans-membrane G protein-coupled receptor5, NLRP3/Caspase-1/GSDMD pathway, pyroptosis

    Received: 17 Jul 2024; Accepted: 02 Sep 2024.

    Copyright: © 2024 Song, Pang, Chen, Wang, Hu, Feng, Wang, Liu and Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Zhixuan Chen, Chengdu University of Traditional Chinese Medicine, Chengdu, China
    Xiaomin Hu, Western Theater General Hospital, Chengdu, 610083, Sichuan Province, China
    Jingzhi Feng, Chengdu University of Traditional Chinese Medicine, Chengdu, China
    Jiancheng Liu, Western Theater General Hospital, Chengdu, 610083, Sichuan Province, China
    Anren Zhang, Shanghai Fourth People's Hospital, Shanghai, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.