Research Paper Volume 13, Issue 9 pp 12973—12995

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

Hong Zeng1,2, *, , Yao Lu1, *, , Meng-Jie Huang1, , Yan-Yan Yang1, , Hua-Yi Xing1, , Xiao-Xie Liu1, , Mou-Wang Zhou1, ,

  • 1 Department of Rehabilitation Medicine, Peking University Third Hospital, Beijing 100191, China
  • 2 Department of Rehabilitation Medicine, Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Huangpu 200011, China
* Equal contribution

Received: October 23, 2020       Accepted: March 27, 2021       Published: May 6, 2021
How to Cite

Copyright: © 2021 Zeng et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


The ketogenic diet has been widely used in the treatment of various nervous system and metabolic-related diseases. Our previous research found that a ketogenic diet exerts a protective effect and promotes functional recovery after spinal cord injury. However, the mechanism of action is still unclear. In this study, different dietary feeding methods were used, and myelin expression and gene level changes were detected among different groups. We established 15 RNA-seq cDNA libraries from among 4 different groups. First, KEGG pathway enrichment of upregulated differentially expressed genes and gene set enrichment analysis of the ketogenic diet and normal diet groups indicated that a ketogenic diet significantly improved the steroid anabolic pathway in rats with spinal cord injury. Through cluster analysis, protein-protein interaction analysis and visualization of iPath metabolic pathways, it was determined that Sqle, Sc5d, Cyp51, Dhcr24, Msmo1, Hsd17b7, and Fdft1 expression changed significantly. Second, through weighted gene co-expression network analysis showed that 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. A ketogenic diet may improve the immune microenvironment and myelin growth in rats with spinal cord injury through reprogramming of steroid metabolism.


SCI: spinal cord Injury; RNA-seq: RNA sequencing; CNS: central nervous system; KD: ketogenic diet; WGCNA: weighted gene co-expression network analysis; PPI: protein-protein interaction; GSEA: gene set enrichment analysis; DEGs: differentially expressed genes; GO: Gene ontology; KEGG: Kyoto Encyclopedia of Genes and Genomes; GS: gene significance; MM: module membership.