Integrative Multi-Omics Reveal the Molecular Architecture and Systemic Burden of Metabolic Syndrome in a Brazilian Cohort

Abstract

Simple Summary Metabolic Syndrome (MetS) is a complex cluster of metabolic disorders that increases the risk of cardiovascular disease and type 2 diabetes. To elucidate its molecular architecture, a study involving 60 adults in Brazil (37 controls and 23 with MetS) integrated clinical, proteomic, metabolomic, and lipidomic analyses. Clinically, HOMA-IR and triglycerides emerged as primary predictors. Proteomic profiling revealed elevated pro-inflammatory markers (ICAM-1 and Vanin-1) and depleted protective ApoD. Metabolomics indicated accumulation of branched-chain and aromatic amino acids, along with decreased 3-hydroxybutyrate. Lipidomics showed an increase in phosphatidylinositols and phosphatidylcholines and a reduction in sphingomyelins. Integrative analysis demonstrated that MetS comprises synchronized and multisystemic molecular dysfunction, characterized by reduction in antioxidant defenses, elevation of inflammatory mediators, lipotoxicity and altered amino acid metabolism consistent with mTORC1 pathway activation. These findings provide a multifactorial molecular signature for diagnosis improvement and the development of personalized therapies.