Dietary naringenin reduces high-fat diet-induced liver injury in largemouth bass by regulating intestinal microbiota and activating the ERα/NLRP3 pathway

The NLR family pyrin domain containing 3 (NLRP3) inflammasome’s activation is essential for fish liver damage brought on by a high-fat diet. Despite naringenin's potential to block NLRP3 inflammasome activation, its preventive effects against fish liver damage caused by a high-fat diet and the underlying processes are yet unknown. To address this, six experimental diets were formulated: a normal-fat diet (10 % lipid, control) and five high-fat diets (18 % lipid, HF) supplemented with 0 %, 0.005 %, 0.01 %, 0.02 %, and 0.04 % naringenin. Each diet was randomly given to three tanks (30 fish/tank). After an eight-weeks feeding trial, the HF did not affect growth performance but induced hepatic and intestinal oxidative stress, ultrastructural damage, hepatocyte apoptosis, hepatic inflammation, and gut dysbiosis ( P < 0.05). Dietary supplementation with naringenin (0.005 %-0.02 %) significantly attenuated hepatic oxidative stress by reducing malondialdehyde (MDA) content and increasing total superoxide dismutase (T-SOD) activity, while also suppressing hepatic inflammation through downregulating the exprssion of NLRP3 inflammasome-related markers ( P < 0.05). Furthermore, 0.02 % naringenin ameliorated hepatic ultrastructure, reduced hepatocyte apoptosis, and improved gut microbiota composition by decreasing Mycoplasma abundance and increasing beneficial genera (e.g., Bacillus , Lactobacillus , and Weissella ) abundance ( P < 0.05). The correlation analysis revealed that estrogen receptor alpha (ERα) was negatively correlated with NLRP3 inflammasome activation and that microbiota enriched in the 0.02 % naringenin group were positively correlated with improved liver health indicators ( P < 0.05). In conclusion, naringenin effectively alleviates HF-induced liver damage in fish by regulating oxidative stress, NLRP3 inflammasome, and gut microbiota, and may serve as a promising feed additive in aquaculture.