Brazilian passion fruit modulates vascular inflammation and gene networks of cholesterol metabolism in overweight individuals

55% of Brazilians are overweight, driving chronic diseases through inflammation, insulin resistance, dyslipidemia, and endothelial dysfunction-key factors in type 2 diabetes and cardiovascular diseases-highlighting the need for preventive strategies. Brazil's rich biodiversity includes <i>Passiflora tenuifila</i> (PS), a native fruit rich in bioactive compounds that may help prevent cardiometabolic diseases. This study investigated its effects on insulin resistance, endothelial function, inflammation, and nutrigenomics in overweight individuals. In a randomized, controlled, crossover study, 16 participants consumed either PS powder or a fiber-matched control for two weeks, with a one-month washout. Blood samples were analyzed for biochemical and transcriptomic changes at the baseline and post-interventions. PS significantly reduced aspartate aminotransferase, IL-6, and sICAM-1, and increased nitrite. HDL levels negatively correlated with insulin, HOMA-IR, and triglycerides. Transcriptomic analysis revealed modulation of 374 genes (protein-coding and non-coding genes), including ABCA1, a key cholesterol efflux regulator. Pathways related to lipid metabolism, inflammation, endothelial function, and insulin signaling were enriched, potentially modulated by PPAR-α and NF-κB transcription factors. These findings suggest that PS may improve endothelial function, reduce inflammation, and enhance lipid and glucose metabolism through complex nutrigenomic modifications, supporting its potential in preventing cardiometabolic disorders. This clinical trial was registered in the Brazilian Registry of Clinical Trials (ReBEC) at https://ensaiosclinicos.gov.br/rg/RBR-8cn9qqg.