Dietary chenodeoxycholic acid alleviates cottonseed oil-induced hepatic lipid deposition and inflammation in juvenile black seabream (Acanthopagrus schlegelii)

The present work conducted an eight-week feeding trail for exploring the dietary chenodeoxycholic acid (CA) affected lipid deposition and inflammation induced by cottonseed oil (CO) within juvenile black seabream ( Acanthopagrus schlegelii ). There were five diets were prepared: FO (containing 8 % fish oil, FO), CO (FO complete replacement by CO), CA1 (CO + 250 mg/kg CA), CA2 (CO + 500 mg/kg CA) and CA3 (CO + 1000 mg/kg CA). Dietary 250 mg/kg CA significantly improve growth performance compare to CO diet. Additionally, 1000 mg/kg CA supplementation reduce the hepatic and muscle linoleic acid and n-6 polyunsaturated fatty acids compared to CO group. Histological observations revealed that dietary CA alleviated CO-induced hepatic steatosis. Moreover, CA supplementation reduced serum and hepatic biomarkers of lipid metabolism and liver function related to CO group. Dietary 250 mg/kg and 1000 mg/kg CA significantly enhanced antioxidant capacity and immune responses compared to the CO diet. Network pharmacology and molecular docking identified peroxisome proliferator-activated receptor alpha (Pparα), cholesterol 7 alpha hydroxylase 1 (Cyp7a1), interleukin-10 (Il-10), and nuclear receptor subfamily 1 group H member 4 (Nr1h4) as core regulatory targets of CA in liver lipid metabolism and inflammation. Real-time quantitative PCR analysis further confirmed that 500 mg/kg CA could ameliorate hepatic lipid metabolism injury by regulating nr1h4 , pparα , cyp7a1 , il-10 and their upstream and downstream related genes. Collectively, these findings demonstrate that dietary CA ameliorates CO-induced hepatic lipid dysregulation and inflammation by modulating Nr1h4/Pparα/nuclear transcription factor κ b (Nf-κB) signaling axis in juvenile black seabream. • Dietary chenodeoxycholic acid (CA) increased growth performance in black searbeam. • The CA supplementation boosted antioxidant and non-specific immune in black seabream. • The supplementing CA in diets enhanced liver lipid metabolism in black seabream. • Dietary CA supplementation improved liver health via Nr1h4/Pparα/Nf-κB pathway.