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

Frontiers in Molecular Neuroscience, 2024 · DOI: 10.3389/fnmol.2024.1466125 · Published: September 12, 2024

Spinal Cord Injury Neurology Nutrition & Dietetics

Simple Explanation

This study investigates how every-other-day fasting (EODF) affects spinal cord injury (SCI) in rats. EODF involves alternating between normal eating and fasting periods. The researchers looked at how EODF influences bile acid metabolism, a process that can affect the central nervous system. They also examined the impact of EODF on pyroptosis, a type of cell death that contributes to inflammation after SCI, and the role of a receptor called TGR5 in this process.

Study Duration

28 days

Participants

30 male Sprague–Dawley rats

Evidence Level

Not specified

Key Findings

1
EODF significantly enhanced the recovery of motor function and reduced pathological damage in SCI rats while controlling weight gain.
2
EODF promoted the secretion of bile acid metabolites, activated TGR5, and inhibited the NLRP3/Caspase-1/GSDMD pyroptosis pathway and inflammation in these rats.
3
EODF could mitigate secondary injury after SCI and foster functional recovery by improving metabolism, activating the TGR5 signaling and inhibiting the NLRP3 pyroptosis pathway.

Research Summary

This study demonstrated that every-other-day fasting (EODF), as a simple and safe dietary intervention, can effectively control both weight and food intake in spinal cord injury (SCI) rats. Crucially, EODF intervention significantly reduces pathological damage post-SCI and enhances motor function. Further research revealed that EODF intervention not only inhibits microglial activation but also elevates serum bile acid levels, thereby increasing the expression of TGR5, which was associated with the inhibition of the NLRP3/Caspase-1/GSDMD pyroptosis pathway and the regulation of pro-inflammatory cytokines IL-18 and IL-1β.

Practical Implications

Therapeutic Potential

EODF presents a promising, non-invasive strategy for enhancing functional recovery after SCI by targeting the NLRP3 pyroptosis signaling pathway and activating TGR5.

Metabolic Regulation

EODF improves metabolism and controls inflammation, potentially offering significant economic and social benefits for clinical SCI treatment by reducing the economic burden on patients and society.

Clinical Translation

Understanding the neuroprotective mechanisms of EODF can facilitate its clinical translational application and broader adoption in SCI treatment protocols.

Study Limitations

1
Further studies are needed to elucidate the key roles of TGR5.
2
The precise mechanism of TGR5 activation by EODF still needs further clarification.
3
Therapeutic mechanisms of EODF in SCI need to be validated through clinical practice.

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