Polyphenol-rich extra-virgin olive oil influences bioenergetics and may modulate NLRP3 inflammasome in PBMCs from children and adolescents with obesity.

Paediatric obesity is characterized by chronic inflammation and immunometabolic dysregulation. Extra-virgin olive oil (EVOO) polyphenols exert antioxidant and immunomodulatory effects that may counteract obesity-related alterations. A 12-week controlled nutritional intervention was conducted in 84 children and adolescents with obesity (BMI > 95th percentile), comparing a Mediterranean diet supplemented with either high-polyphenol EVOO (P-EVOO) or refined olive oil (R-OO). Anthropometric and biochemical parameters were evaluated at baseline and study completion. In peripheral blood mononuclear cell (PBMC) of a sub-cohort, bioenergetic analyses, gene expression related to mitochondrial biogenesis, antioxidant defence, and NLRP3 gene expression were assessed. Both groups exhibited significant reductions in BMI, waist circumference, LDL cholesterol, triglycerides and uric acid. A significant reduction in insulin resistance was observed exclusively in the P-EVOO group. In PBMCs, P-EVOO enhanced mitochondrial respiration and ATP production, associated with a metabolic shift toward oxidative phosphorylation. This was accompanied by increased mitochondrial biogenesis and activation of the Nrf2-SOD2 antioxidant axis. P-EVOO upregulated NLRP3, IL-1β, CASP8 and CASP1 gene expression, without IL-18 or GSDMD increase, suggesting a distinct expression pattern of alternative NLRP3 inflammasome-associated markers. These findings indicate that P-EVOO could ameliorate metabolic health and mitochondrial bioenergetics in paediatric obesity, promoting an oxidative immunometabolic phenotype potentially associated with controlled inflammasome transcriptional regulation.