Abstract
Excessive dietary fat intake disrupts lipid metabolism and induces oxidative stress and inflammation in aquatic species, impairing growth and health. In Takifugu obscurus, a widely cultivated fish species in China, fat predominantly accumulates in the liver, making this species particularly susceptible to hepatic lipid metabolism disorders. Lycium barbarum polysaccharides (LBPs), as a biologically active macromolecule, are capable of regulating lipid metabolism. Therefore, in this study, we aimed to investigate the regulatory effects of dietary LBP supplementation on lipid metabolism, hepatic function, intestinal microbiota, and metabolomic profiles in high-fat diet (HFD)-fed T. obscurus. A control diet comprising 80 g/kg fat and five HFDs (150 g/kg fat) supplemented with 0, 0.5, 1.0, 1.5, and 2.0 g/kg LBP was administered to 630 juvenile T. obscurus individuals for 56 days. Serum biochemistry, hepatic antioxidant indices, gene expression, intestinal microbiota, and liver metabolomics were analyzed. HFD feeding significantly increased serum triglyceride (TG), total bile acid (TBA), total cholesterol (TCHO), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and hepatic malondialdehyde (MDA) levels while decreasing high-density lipoprotein cholesterol (HDL-C) and total superoxide dismutase (T-SOD) levels. Conversely, LBP supplementation significantly reversed these effects and improved the antioxidant capacity. LBP supplementation resulted in the downregulation of lipid synthesis and inflammatory gene expression and upregulation of lipid catabolism and antioxidant genes. Microbial and metabolomic analyses indicated that LBP supplementation restored gut microbial balance, enhanced diversity, and normalized bile acid and glycerophospholipid metabolism, exhibiting the most pronounced effects at a dose of 1.5 g/kg. In conclusion, LBP effectively mitigates HFD-induced lipid metabolism disorders in T. obscurus. Furthermore, based on the strong correlations observed between the gut microbiota and differential metabolites, we speculate that the gut-liver axis may play a potential role in the regulatory effects of LBP, providing valuable clues for further investigation into the underlying molecular mechanisms.