Astaxanthin-rich Nannochloropsis oculata mitigates high-fat diet-induced liver dysfunction in zebrafish by modulating lipid metabolism and oxidative stress.

High-fat diets (HFDs) are widely used in aquaculture but may adversely affect fish liver health by disturbing lipid metabolism and promoting oxidative stress. This study investigated the protective effects of Nannochloropsis oculata enriched with astaxanthin on zebrafish (Danio rerio) fed an HFD. All zebrafish (n = 135) were divided randomly into three groups: conventional diet (CD), high-fat diet (HFD), and HFD supplemented with 2% N. oculata (HFD + NO). After a four-week feeding trial, growth performance, hepatosomatic index, liver oxidative stress markers, and expression of immune cytokine genes were evaluated. HFD group exhibited significantly increased hepatic lipid accumulation, elevated serum triglycerides and total cholesterol, and increased liver marker enzymes. These changes were accompanied by reduced antioxidant enzyme and non-enzymatic antioxidant activity, heightened oxidative stress, and upregulated pro-inflammatory cytokine expression (il-1β and il-8). Histological analysis confirmed hepatic steatosis and structural deterioration. Conversely, N. oculata supplementation significantly alleviated these effects by reducing hepatic lipid deposition, restoring antioxidant defenses, and downregulating pro-inflammatory cytokines while upregulating anti-inflammatory responses (IL-10 and TGF-β). These protective effects are attributed to astaxanthin's role in boosting mitochondrial β-oxidation, suppressing lipogenesis, and modulating inflammatory pathways. These findings suggest that N. oculata is a promising functional feed additive for mitigating diet-induced liver dysfunctions in aquaculture. Further research is needed to elucidate its molecular mechanisms and assess its long-term benefits across diverse aquatic environments.