Abstract
Exposure to copper (Cu) has been associated with metabolic disorders in animals and humans, but the underlying mechanism remains unclear. One-day-old broiler chickens, numbering a total of 192, were nourished with dietary intakes that contained varying concentrations of Cu, specifically 11, 110, 220, and 330 mg/kg of Cu, for a period extending over a duration of 7 wk. As a result of the study, Cu exposure resulted in vacuolization, fragmentation of mitochondria cristae, and the increase of autophagosomes in hepatocytes. Metabolomics analysis illustrated that Cu caused a total of 59 different metabolites in liver, predominantly associated with the glycerophospholipid metabolic pathway, leading to metabolic disruption. Moreover, high-Cu diet markedly reduced the levels of AMPKα1, p-AMPKα1, mTOR, and p-mTOR and enhanced the expression levels of the autophagy-related factors (Atg5, Dynein, Beclin1, and LC3-II). Overall, Cu exposure caused chicken liver injury and resulted in disturbed metabolic processes and mediated autophagy primarily through the AMPK-mTOR axis.