Dietary sodium butyrate promotes mitochondrial homeostasis by regulating PCK2 and PPARGC1α to alleviate liver ammonia metabolism disorder in juvenile yellow catfish (Pelteobagrus fulvidraco)

This study aimed to investigate whether sodium butyrate (SBE) alleviates chronic ammonia toxicity through the restoration of mitochondrial structure and function in yellow catfish. Juvenile yellow catfish (initial weight 4.47 ± 0.02 g) were randomly assigned to four groups for 8 wk: CON (0 g/kg SBE; 0 mg/L total ammonia nitrogen, T-AN), AM (0 g/kg SBE; 50 mg/L T-AN), SB (2.00 g/kg SBE; 0 mg/L T-AN), and SBAM (2.00 g/kg SBE; 50 mg/L T-AN). Compared with the AM group, the SBAM group showed significantly increased weight gain rate ( P < 0.001), serum superoxide dismutase (SOD; P = 0.002), and catalase (CAT; P = 0.007) activities, and significantly decreased serum ammonia level ( P < 0.001), and total cholesterol ( P = 0.001). Metabolomic profiling revealed that CAE disrupted mitochondrial-associated arginine biosynthesis, tricarboxylic acid cycle, and fatty acid degradation pathways. This disruption was characterized by decreased levels of key metabolites (arginine, succinic acid, and palmitoyl-CoA) and genes ( cps1 , mdh2 , and cpt1ab ) in AM group than in CON group ( P < 0.05), indicating impaired mitochondrial function and ammonia metabolism. Mechanistically, compared with CON group, AM group downregulated PCK2 and PPARGC1α ( P < 0.05), reducing phosphatidylcholine and phosphatidylethanolamine and elevating lyso-phosphatidylcholine and lyso-phosphatidylethanolamine ( P < 0.05), indicating mitochondrial membrane disruption. The SBE reversed these alterations by enhancing glycerophospholipid synthesis, restoring mitochondrial membrane integrity and mitochondrial biogenesis. Consequently, compared with AM group, the abundance of mitochondrial CPS1 ( P = 0.005) in SBAM group, the rate-limiting enzyme initiating urea synthesis, was restored, thereby facilitating urea cycle activation and enhancing ammonia detoxification. These findings support SBE as a functional feed additive for enhanced ammonia tolerance in aquaculture.