Identification of key metabolic pathways and biomarkers in hypertensive metabolic syndrome through integrative multi-omics analysis

Background and purpose: Metabolic syndrome (MetS), encompassing conditions such as diabetes, dyslipidemia, obesity, and hypertension (HTN), is a significant risk factor for refractory HTN. However, the molecular mechanisms linking MetS to HTN remain poorly understood. The aim of our research is to identify the key metabolic pathways and biomarkers in hypertensive MetS through integrated multi-omics analysis. Methods: We conducted an integrative multi-omics analysis, combining plasma metabolomics and leukocyte transcriptomics from four groups: hypertensive MetS (HT-MetS), normotensive MetS (NT-MetS), isolated HTN, and healthy controls (CON). Key metabolites were identified using orthogonal partial least squares discriminant analysis (OPLS-DA) and random forest analysis. Transcriptomic profiling was performed to examine dysregulated metabolism-related genes. Pathway enrichment analyses were conducted, and multi-omics integration analyses were performed to construct molecular networks and identify joint metabolic pathways and clusters. Results: Distinct biomarkers differentiating HT-MetS from HTN were identified, including octanal, diethyl phosphate, L-fucose, and arachidonic acid. HT-MetS was further distinguished from NT-MetS by markers such as porphobilinogen and 4-hydroxyretinoic acid. The predominant differential metabolites were carboxylic acids, organooxygen compounds, and fatty acyls. Transcriptomic analysis highlighted key pathways, including carbon metabolism, inositol phosphate metabolism, and fatty acid. Integrated multi-omics analysis revealed that lipid and carbohydrate metabolic pathways play central roles in the pathophysiology of HT-MetS. Conclusion: This study provides valuable insights into the metabolic mechanisms underlying HT-MetS and suggests potential biomarkers for early diagnosis and therapeutic interventions.