The crosstalk between fatty acid metabolism disorder and mitochondrial dysfunction is involved in hepatotoxicity co-induced by cadmium and molybdenum in ShaoXing duck (Anas platyrhyncha) livers.

Abstract

Excessive molybdenum (Mo) and cadmium (Cd) exert negative influences on organism. Our prior experiments attested that Mo and Cd brought liver damage in ShaoXing ducks (Anas platyrhyncha); this injury mechanism has not yet been fully clarified. Hence, the hepatotoxicity mechanisms of Mo and Cd were roundly analyzed by network toxicology in the study, the analysis confirmed that Mo and Cd primarily induce liver injury through lipid metabolism dysregulation, oxidative stress, and mitochondrial dysfunction. Further validation demonstrated that Mo and/or Cd upregulated fatty acid synthesis, reduced PPARβ/δ-mediated fatty acid β-oxidation, promoted free fatty acids (FFA) content and mitochondrial reactive oxygen species (mtROS) level, impaired integrality of mitochondrial membrane and mitochondrial function, thereby causing fatty acid metabolism disarray and mitochondrial dysfunction. Both PPARβ/δ activator GW0742 and mtROS inhibitor ROS-IN-1 could alleviate the changes of above these indexes. Collectively, findings from this research showed that Cd and Mo additively caused crosstalk between fatty acid metabolism disarray and mitochondrial dysfunction, thus inducing liver injury in ducks.