Construction of Potential Transcription Factor-miRNA-mRNA Regulatory Network in Obesogenic Memory

Background: The phenomenon of “former obesity history-weight loss-easy to regain weight” is referred to as obesogenic memory. Despite its significance, the underlying mechanism remains poorly understood. This study aimed to construct a potential transcription factor (TF)-miRNA-mRNA network in obesogenic memory. Methods: Microarray datasets for miRNA (GSE61005) and mRNA (GSE8586 and GSE76944) were obtained from the Gene Expression Omnibus database, comparing individuals with a history of obesity to those who have never been obese. Differentially expressed genes (DEGs) and differentially expressed miRNAs (DEMs) were analyzed. Subsequent analyses involved gene ontology and pathway enrichment assessments and the construction of a TF-miRNA-mRNA network. Results: We discovered 63 DEGs and 48 DEMs, with DEGs predominantly linked to neutrophil chemotaxis and chemokine activity. Pathway analysis revealed enrichment in cytokines and inflammatory responses. Module network analysis identified 14 hub genes. The TF-miRNA-mRNA network involved two TFs, eight miRNAs, and nine mRNAs. Egr2 emerged as a key regulator of most miRNAs, whereas CLEC4E, CXCL1, and SERPINB6B were potential targets of identified miRNAs. Conclusion: Two hub TFs, eight hub miRNAs, nine hub mRNAs, and several potential TF-miRNA–mRNA interactions were identified in obesogenic memory. These TF-miRNA-mRNA interactions shed light on obesogenic memory mechanisms and offer promising therapeutic targets.