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.