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

Abstract

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.

Ketogenic therapy towards precision medicine for brain diseases

“…Moreover, KD showed a powerful anti-inflammatory effect. Ketones, especially BHB, have been reported to reduce cardiac inflammation, decrease the development of heart failure ( 54 ), and ameliorate the inflammation after spinal cord injury ( 55 ). KD also has a promising role in inhibiting NOD-like receptor protein 3 (NLRP3) inflammasome assembly, reducing oxidative damage, and attenuating inflammatory mediators produced by infiltrating macrophages ( 56 ).…”

Six-month periodic fasting does not affect somatosensory nerve function in type 2 diabetes patients

“…Moreover, DSPN characterization was based only on clinical neuropathy scores and nerve conduction velocity analysis, whereas no data on quantitative sensory testing or MRI nerve lesions were collected. Diet intervention that induce ketogenesis and lipolysis, either through fat-favorable composition of energy sources, or through fasting and caloric intake reduction, have beneficial disease-modifying effects on different neurological disorders including epilepsy (12), multiple sclerosis (13) and central spine injury in humans (14) and in animal models (15) mediated through alterations in extracellular signalregulated kinases (ERK)-and mammalian target of rapamycin (mTOR)-signaling (16) and in opioid-receptor expression (17). On the other hand, diet intervention in diabetes patients should be considered carefully, since rapid decrease of glycemia increases the risk of treatment-induced neuropathy in diabetes (TIND) (18).…”