Dietary hesperetin mitigates high-fat-induced growth suppression, intestinal lipid accumulation, oxidative stress, and inflammation in largemouth bass (Micropterus salmoides)

This study evaluated the effects of dietary hesperetin (Hes) on growth performance, intestinal lipid deposition, oxidative stress, and inflammatory responses in largemouth bass ( Micropterus salmoides ) fed high-fat diets. A 2 × 3 factorial design was employed, consisting of two dietary lipid levels (9.85% and 17.85%) and each lipid with three hesperetin supplementation (0, 1.25, and 2.5 g/kg). High-purity hesperetin with constant chemical characterization was purchased from Aladdin Industrial Corporation (purity >97%). Six isonitrogenous diets were formulated and fed to juvenile largemouth bass (6.94 ± 0.10 g) for 10 weeks. Significant interactions between dietary lipid and hesperetin levels were observed for final body weight (FBW), weight gain (WG), specific growth rate (SGR), feed intake (FI), feed conversion ratio (FCR), and viscerosomatic index (VSI). Under high-fat condition, hesperetin improved FBW, WG, and SGR, while reducing FCR and VSI; however, opposite trends occurred at the lower lipid level. Dietary lipid and hesperetin interacted to influence intestinal villus, Srebp1 and ER-ApoB48 protein abundance, and expression of lipid metabolism-related genes ( fas , dgat2 , pparγ , abca1 , mttp , apob ). HFD significantly elevated TG content, and hesperetin decreased TG levels at both lipid levels. At both lipid levels, hesperetin downregulated mRNA expression of lipogenic genes ( fas , dgat2 , pparγ , abca1 ) and protein expression of Srebp1, increased villus width, and upregulated mttp and apob mRNA expression, although its ER-ApoB48 protein expression increased only under high-fat condition. Antioxidant enzyme activities (CAT, T-SOD), total antioxidant capacity (T-AOC), and mRNA expression of nrf2 , sod1 , sod2 , cat , gpx1 , and gpx2 were enhanced by hesperetin supplementation. In contrast, MDA content and expression of keap1 and pro-inflammatory cytokines ( tnf-α , stat1 , il-1β , il-6 , il-8 ) decreased, and anti-inflammatory il-10 expression increased at both lipid levels. Overall, hesperetin supplementation effectively mitigated HFD-induced inhibition in growth performance, intestinal lipid metabolism, oxidative status, and inflammatory signaling in largemouth bass. These findings support the application of hesperetin as a functional dietary additive for improving intestinal health in fish species.