Naringenin alleviates lipid accumulation and inflammation, and promotes hepatic-intestinal health of Largemouth bass (Micropterus salmoides) fed with high-fat diet

Naringenin (NGN), a flavonoid compound abundantly found in citrus fruits, exhibits anti-inflammatory, anti-oxidative activities, and hypolipidemic properties. However, nowadays, NGN is mainly used to inhibit the occurrence of viral diseases in aquatic animals by injection as an immunosuppressant, and its safety and other physiological effects as a feed additive have not been sufficiently investigated. This study elucidates how naringenin (NGN) mitigates the negative impacts exerted by a high-fat diet (HFD) on Largemouth bass ( Micropterus salmoides ) from hepatic and intestinal perspectives. After an 8-week feeding trial, the NGN groups had a significant effect on growth performance compared to the HFD group, and significantly decreased the lipid content of the whole body. Secondly, NGN significantly decreased the levels of triglycerides and total cholesterol in serum compared with the HFD group, down-regulated the lipogenesis-related genes, and significantly up-regulated the lipolysis-related genes. Furthermore, hepatic injury markers alanine transaminase and aspartate transaminase were also significantly decreased. Additionally, NGN significantly enhanced the antioxidant capacity of the liver, down-regulated the gene expression of pro-inflammatory factors, and up-regulated the anti-inflammatory factors. There were remarkable changes in the structure of the gut microbiota, where the biomarker of the Na1 group was Dyella , and the main ones in the Na2 group were Asinibacterium , Methylovirgula , Mesorhizobium, and Meiothermus . The function of the gut microbiota in the NGN was more enriched in the fatty acid biosynthesis pathway compared to the high-fat diet. To conclude, the supplementation of NGN to HFD can significantly reduce hepatic lipid deposition and alleviate liver damage, as well as improve gut health status. Among them, the addition of 0.007 % naringenin exhibited a better effect. The results of this study will be used to help reduce the negative effects of an HFD within the aquaculture sector and hold the potential to be regarded as a promising eco-friendly feed additive for aquaculture. • First demonstration of naringenin’s (NGN) hepatoprotective and anti-inflammatory effects in Largemouth bass fed high-fat diet (HFD). • NGN supplementation significantly reduced hepatic lipid accumulation and oxidative stress in HFD-fed fish. • NGN modulated gut microbiota composition, enhancing intestinal health in Largemouth bass. • Providing novel evidence for citrus flavonoids as sustainable functional feed additives in aquaculture. • Offering practical solution to mitigate HFD-induced metabolic disorders in intensive fish farming.