Transcriptome-Based KEGG Pathway Analysis Identifies Altered Hepatic Immune Signaling in Response to High Iron Intake

Iron deficiency is a major global health concern, and iron supplementation is widely used to restore iron status; however, excessive intake may disrupt copper homeostasis and lead to secondary physiological disturbances.Although iron-copper imbalance has been shown to affect hepatic lipid metabolism, the impact of this imbalance on hepatic immune regulation remains unclear.This study investigated alterations in hepatic immune signaling under conditions of dietary iron and copper imbalance using transcriptome-based Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis.Male rats were fed diets containing different levels of iron and copper for 5 weeks.Hepatic transcriptomic profiles were obtained using RNA sequencing, and differentially expressed genes were identified by comparing the adequate iron and copper group with the high iron and low copper group.KEGG pathway mapping was performed to evaluate immune-related pathways, focusing on T cell receptor signaling and the intestinal immune network for immunoglobulin A (IgA) production.Pathway analysis indicated increased expression of interleukin (IL)-2 and IL-4 and decreased expression of IL-10, suggesting a shift toward a pro-inflammatory immune profile.Reduced expression of programmed cell death protein 1 further implied attenuated negative regulation of T cell activation.These findings suggest that iron-copper imbalance associated with high iron intake may influence hepatic immune signaling.