Multi-omics profiling reveals dynamic glucolipid reprogramming and immune homeostasis governing early hepatopancreatic adaptation in mandarin fish (Siniperca chuatsi) fed formulated diets

While long-term hepatic responses to formulated feeds are well-documented in mandarin fish, early adaptive mechanisms remain unclear. Mandarin fish were equally allocated to control ( Paramisgurnus dabryanus ) and test (acclimated to formulated feed) groups, sampled at 1 and 3 weeks. Formulated diet feeding for 1 and 3 weeks significantly enhanced growth performance but induced early signs of dietary stress, including microvesicular lipid deposition, vascular congestion, and elevated triglyceride and cholesterol levels. Gene profiling revealed upregulated hepatopancreatic lipid genes ( DHCR7, DHCR24, SQLE ) and antioxidant GSTZ1 ( P < 0.05), but downregulated inflammatory IL1RA and ER stress marker HSPA5 ( P < 0.05) in formulated feed groups at both timepoints. Comparative analysis of DEGs identified six overlapping KEGG pathways between the 1 week (AD1 compared with LF1) and 3 weeks (AD2 compared with LF2) feed groups. Four pathways were associated with glycolipid metabolism (Glycolysis/Gluconeogenesis, Glycerophospholipid metabolism, Steroid biosynthesis, PPAR signaling pathway), while two pertained to immune regulation (Glycine, serine and threonine metabolism; Valine, leucine and isoleucine degradation). Metabolomic analysis revealed 124 significantly altered metabolites in the AD1 group, including upregulated glycerophospholipids (e.g., PC(P-16:0/PGE2), PE(P-18:0/PGE2); P < 0.01) suggesting membrane remodeling, and downregulated 3α,7α-dihydroxycoprostanic acid ( P < 0.01) indicating disrupted bile acid metabolism. In the AD2 group, 240 differential metabolites were identified, with elevated 9,10-/12,13-dihydroxyoctadecenoic acid ( P < 0.01) reflecting lipid peroxidation, and increased Formononetin 7-O-glucuronide ( P < 0.01) indicating antioxidant activation. Multi-omics integration demonstrated suppressed carbohydrate metabolism but enhanced lipid pathways (e.g., steroid biosynthesis, glycerophospholipid metabolism) after short-term formulated feeding. Overall, these changes illustrate a coordinated adaptive response involving lipid metabolic activation, reduced carbohydrate utilization, and improved immune regulation. • First multi-omics characterization of early hepatopancreatic adaptation to formulated feed in mandarin fish. • Six conserved pathways drive adaptation: four glycolipid-metabolic and two immune-regulatory. • Coordinated stress response: reduced ER stress and inflammation plus elevated antioxidant defense. • Metabolic-immune reprogramming: Carbohydrate suppression with lipid activation enables immune enhancement.