Ketogenic diet-mediated steroid metabolism reprogramming improves the immune microenvironment and myelin growth in spinal cord injury rats according to gene and co-expression network analyses

AGING, 2021 · DOI: · Published: May 6, 2021

Spinal Cord Injury Genetics Nutrition & Dietetics

Simple Explanation

A ketogenic diet (KD) is a high-fat, low-carbohydrate, moderate-protein diet that results in the prominent production of ketone bodies (KBs: β-hydroxybutyrate [BHB], acetoacetate [ACA] and acetone). This study is the first to demonstrate that the KD significantly promotes the reprogramming of steroid metabolism in the treatment of SCI at the transcriptional level. Moreover, a comprehensive analysis of the KD through WGCNA indicates the improvement of the SCI immune microenvironment and reduction in inflammation.

Study Duration

4 weeks

Participants

32 8-week-old male Sprague-Dawley rats

Evidence Level

Not specified

Key Findings

1
A ketogenic diet significantly improved the steroid anabolic pathway in rats with spinal cord injury.
2
Rats fed a ketogenic diet showed a significant reduction in the expression of genes involved in immune-related pathways, including those associated with immunity and infectious diseases.
3
Myelin sheath area in the SCI_KD group was significantly larger than that in the spinal cord injury with standard diet (SCI_SD) group.

Research Summary

This study used RNA-seq to understand and identify DEGs in SCI rats fed a KD and then examine which biological signalling pathways can explain the protective effects of the KD diet on SCI rats. KD significantly increased the steroid anabolic pathway in rats with SCI. Through cluster analysis, PPI analysis and the iPath metabolic pathway visualization, we concluded that Sqle, Sc5d, Cyp51, Dhcr24, Msmo1, Hsd17b7, and Fdft1 expression changed significantly in the pathway. rats fed a KD displayed significantly reduced immune-related pathways, including immune diseases and infectious diseases. In addition, examining the data from the SCI_KD and SCI_SD groups and existing MSigDB analysed by GSEA, we concluded that SCI_KD is significantly negatively correlated with inflammatory cytokines and their receptors.

Practical Implications

Steroid Metabolism Reprogramming

KD may mediate steroid metabolism reprogramming to treat SCI in rats.

Myelin Sheath Regeneration

KD facilitates myelin membrane synthesis and promotes myelin sheath regeneration.

Improved Immune Microenvironment

KD can improve the body's immunity and reduce infection and inflammation after SCI.

Study Limitations

1
Study cannot directly prove a correlation between KD-mediated reprogramming of steroid metabolism and neuroimmunity.
2
Significantly expressed genes in the steroid synthesis pathway need to be further examined in future studies to determine if they are related to SCI efficacy.
3
Not specified

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