Lipopeptides modulate lipid metabolism and immune performance in largemouth bass (Micropterus salmoides) across dietary lipid levels

Lipopeptides are versatile surface-active natural products that act as emulsifiers, enhance lipid utilization, and exhibit broad-spectrum antimicrobial properties. Whether lipopeptides have the potential to improve energy efficiency and fight bacterial infection in largemouth bass (<i>Micropterus salmoides</i>) has not been reported. In this study, a total of 300 juvenile largemouth bass (initial body weight 14.67 ± 0.01 g) were randomly divided into four groups with five replicates per group (<i>n</i> = 5), each replicate consisting of 30 fish. The fish were fed four experimental diets for 10 weeks: 10.50% lipid (low-lipid [LL]), 10.50% lipid + 0.05% lipopeptides (low-lipid with lipopeptides [LLLP]), 13.00% lipid (high-lipid [HL]), and 13.00% lipid + 0.05% lipopeptides (high-lipid with lipopeptides [HLLP]). Two-way ANOVA showed neither lipid levels nor lipopeptides had a significant effect on survival rate and weight gain (<i>P</i> > 0.05). However, the largemouth bass fed low-lipid diets exhibited significantly higher feed intake to meet energy demands, resulting in an increased feed conversion ratio (<i>P</i> = 0.004), which was then decreased after lipopeptide supplementation (<i>P</i> = 0.061). High-lipid levels led to a significant increase in plasma total cholesterol (TC) and liver lipid content (<i>P</i> < 0.001), and the addition of lipopeptides significantly improved the above conditions (<i>P</i> < 0.001). Mechanistically, lipopeptides upregulated lipid catabolism (hormonesensitive triglyceride lipase [<i>Hsl</i>], <i>P</i> < 0.001) and fatty acid oxidation genes (carnitine palmitoyltransferase 1 <i>α</i> [<i>Cpt1α</i>], <i>P</i> = 0.004), while suppressing lipogenesis gene (fatty acid synthase [<i>Fasn</i>], <i>P</i> = 0.045). Pathway analysis revealed that lipopeptides coordinately regulated energy metabolism by involving AMP-activated protein kinase (AMPK) energy sensing and cyclic-AMP (cAMP) response element-binding protein (Creb) signaling cascades. In an <i>Edwardsiella tarda</i> challenge, lipopeptide supplementation significantly reduced intestinal pro-inflammatory factors (interleukin [IL]-8 , <i>P</i> = 0.007 and IL-1β, <i>P</i> = 0.006) and enhanced immune function, as evidenced by elevated levels of anti-inflammatory transforming growth factor-β1 (TGF-β1; <i>P =</i> 0.011) and immunoglobulin M (IgM; <i>P</i> = 0.003). This study provides a comprehensive exploration of lipopeptide-mediated regulatory mechanisms under different dietary lipid levels, highlighting their potential for optimizing feed formulations and improving lipid metabolic health in aquaculture species.