ANTI-INFLAMMATORY AND BEHAVIORAL EFFECTS OF EXTRA VIRGIN OLIVE OIL SUPPLEMENTATION IN OBESE RATS WITH A DEPRESSIVE-LIKE PHENOTYPE: A SEX-SPECIFIC APPROACH

Aims: This study investigates whether extra virgin olive oil (EVOO) supplementation attenuates hippocampal inflammation and depressive-like behavior in high-fat diet-induced obesity model, considering both sexes. Methods: At 21 days (CEUA-UFRGS 41855), male and female Wistar rats were allocated into groups: (1) Standard chow (SC); (2) SC + EVOO; (3) HFD; (4) HFD + EVOO. EVOO was gavage daily (dose of 1.3mL/Kg). Consumption and body weight were monitored weekly. Depressive-like behavior was assessed by the forced swim and splash test. Hippocampal cytokine (IL-1β, IL-6, TNF-α) levels and glial fibrillary acidic protein (GFAP) were measured by ELISA. Immunoreactivity for ionized calcium-binding adapter molecule 1 (IBA-1) and toll-like receptor 4 (TLR-4) was analyzed in the hippocampal CA1 area. Cluster analysis using Z-scores identified neurobiological profiles based on inflammation and behavior among the animals. Results: HFD-males presented higher body weight (p=0.001) and HFD+EVOO females decreased body weight (p=0.002). EVOO supplementation prevented depressive-like behavior in males (p=0.049) and increased grooming for both sexes (p=0.004 males, p=0.001 females). EVOO supplementation significantly lowered IL-6 (p=0.001), IL-1β (p=0.001), and TNF-α (p<0.001) hipocampal levels of obese females. EVOO supplementation significantly reduced hippocampal GFAP (p=0.010) and IL-6 (p=0.003) levels in obese male rats. EVOO supplementation reduced IBA-1 (p=0.048) and TLR-4 (p=0.013) immunoreactivity for males. Cluster analysis showed sex-specific responses, with greater heterogeneity in females and a distinct isolated HFD-fed males cluster marked by elevated neuroinflammatory and behavioral markers. Conclusions: EVOO supplementation, a nutrititional approach, attenuated HFD-induced obesity, improving depressive-like behavior and reducing inflammation in both sexes, while revealing sex-specific differences.