Conjugated Linoleic Acid Alleviates Hepatic Steatosis and Liver Damage in Estradiol-Induced FLHS Roosters by Reshaping Lipid Metabolism and Inhibiting the MAPK/NF-κB-Mediated Inflammation Cascade

Abstract

Simple Summary Fatty liver hemorrhagic syndrome (FLHS) causes substantial economic losses in laying-hen production. Numerous studies have focused on nutritional imbalance-induced FLHS and the potential underlying mechanisms. The roles of hormonal homeostasis disturbance in the onset and progression of FLHS are unclear. Conjugated linoleic acid (CLA) can relieve estradiol-induced FLHS in chickens, yet its underlying molecular mechanism remains unclear. In this study, we established an estradiol-induced FLHS model using male Hy-line white chickens and combined hepatic transcriptomics and metabolomics to explore the hepatoprotective mechanism of CLA. CLA improved serum lipid profiles, reduced hepatic lipid accumulation, and enhanced hepatic antioxidant capacity in FLHS chickens. Multi-omics analyses revealed that CLA reshaped hepatic metabolic signatures and altered gene expression related to lipid metabolism and inflammation. Key genes (FASN, JUN, FADS2) and critical metabolites (ubiquinol, L-carnitine, 15-hydroperoxyeicosa-8Z,11Z,13E-trienoate) were identified, indicating the potential involvement of MAPK/NF-κB, PPAR, and insulin signaling pathways in CLA-mediated liver protection. This work provides preliminary mechanistic clues and candidate targets for developing CLA-related functional feed additives against poultry FLHS.