A thorough examination of GWAS data on dysregulation of miRNA networks and lipid metabolism pathways in metabolic syndrome

Abstract

Aim: Metabolic syndrome (MetS) is a clustering of risk factors that increases susceptibility to type 2 diabetes and cardiovascular disease. This study aimed to perform a comprehensive bioinformatic analysis of genomic data to elucidate molecular pathways underlying MetS. Methodology: GWAS data from previous MetS studies were analyzed using TargetScan, miRTarBase, Reactome Pathways, KEGG, protein–protein interaction (PPI) networks, and Gene Ontology (GO) mapping. Integration of these datasets identified key miRNAs, metabolic pathways, biological processes, and molecular activities associated with MetS. Results: hsa-miR-126 was markedly enriched and strongly correlated with MetS. Pathway analysis highlighted cholesterol metabolism (p <0.05) and plasma lipoprotein remodeling (p <0.05) as significant contributors. GO analysis revealed triglyceride homeostasis (p <0.05) and very-low-density lipoprotein particle remodeling (p <0.05) as a key biological processes. Metabolomic analysis established strong links between triacylglycerol and glycerol metabolism. Lipid transport and metabolism emerged as central to MetS pathogenesis, with notable enrichments for high-density lipoprotein particles (p <0.05) and phosphatidylcholine-sterol O-acyltransferase activator activity (p <0.05). Interpretation: This comprehensive analysis indicates that dysregulation of lipid metabolism is a major pathway in MetS, with specific miRNAs functioning as critical regulatory molecules. These insights suggest potential therapeutic strategies targeting miRNA-mediated regulation of lipid metabolism. Key words: Cholesterol homeostasis, Lipid metabolism, Lipoprotein remodeling, Metabolic syndrome, miRNA regulation