Thirty Weeks Dietary Nano‐Selenium Improves Liver Health of Grass Carp ( <i>Ctenopharyngodon idella</i> ) Revealed by Transcriptomics and Metabolomics

Grass carp (Ctenopharyngodon idellus), China's most valuable freshwater aquaculture species, exhibits growth and nutrient utilization efficiency that are highly dependent on feed quality. After macronutrient balancing, nano-selenium (nano-Se) supplementation becomes critical for enhancing health and profitability. Although nano-Se has been observed to alleviate oxidative stress and inflammation, the molecular mechanisms underlying its hepatoprotective effects following long-term administration remain systematically uncharacterized. To fill this gap, this study utilized transcriptomic and metabolomic technologies to investigate the beneficial alterations in the liver of grass carp following 30 weeks of nano-Se feeding. Ninety juvenile grass carp were randomly allocated to either a control group (basal diet) or a nano-Se group (basal diet + 0.6 mg/kg nano-Se); livers were harvested for omics analyses at the end of the 30-week feeding period. Transcriptomic analysis initially identified 533 differentially expressed genes (110 up-regulated, 423 down-regulated). Gene Ontology (GO) functional enrichment analysis indicated that these genes were primarily involved in biological processes such as metabolic processes, biological regulation, and stress response, suggesting that nano-Se broadly regulates hepatic metabolic activity and stress adaptability. Further Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed significant enrichment in the "protein digestion and absorption" pathway. Key genes in this pathway, including collagen VI α1/2 (COL6A1/2), elastase ELA2/3 L, and amino acid transporters SLC3A1 and SLC7A9, were significantly down-regulated, indicating that nano-Se may mitigate oxidative stress-induced micro-damage in hepatocytes, thereby reducing the liver's demand for damage repair and fibrotic processes. Metabolomic analysis detected 1404 metabolites, with 267 differentially metabolites (198 up-regulated, 69 down-regulated) spanning multiple metabolic categories such as amino acids, lipids, and cofactors. Glycerophospholipids (GP) and sphingolipids (SP) were significantly up-regulated, while bile acid metabolites were down-regulated. Related metabolic pathway analysis showed that "glycerophospholipid metabolism" and "linoleic acid metabolism" pathways were significantly activated. Glycerophospholipids and sphingolipids are major components of cell membranes; their increased levels may enhance the integrity and stability of hepatocyte membranes. Concurrently, enhanced linoleic acid metabolism may contribute to energy supply and inflammation regulation. These changes collectively suggest that nano-Se may improve hepatic redox homeostasis and metabolic balance by remodeling hepatocyte membrane lipid composition and optimizing energy metabolism pathways. Collectively, nano-Se alleviates oxidative injury and maintains metabolic homeostasis in the grass-carp liver through the coordinated modulation of amino-acid, lipid and immune-related pathways, thereby providing a theoretical basis for its long-term, safe application in aquafeeds; future work is still required to verify these findings by measuring antioxidant-enzyme activities and to optimize dosage through graded-dose experiments.