The role of lipid metabolism imbalance in copper-induced PANoptosis in broiler kidney

Abstract

Copper (Cu) is widely used in both agriculture and industry and may pose toxic risks to animals and public safety if overused. In order to gain a more profound insight into the nephrotoxic effects of Cu, a detailed analysis was performed of its impact on renal PANoptosis, with particular attention being paid to the possible involvement of lipid metabolism disorders in the kidney. In this study, one-day-old chicks were fed diets with varying Cu levels (11, 110, 220, and 330 mg/kg) over a period of 49 days. Our findings indicated that excessive Cu exposure led to vacuolar degeneration, fibrosis and mitochondrial damage in the kidney. Moreover, the assay results demonstrated that elevated Cu levels led to disturbances in lipid synthesis and catabolism, as well as the activation of lipophagy in broiler kidneys. Concurrently, genetic and protein analysis demonstrated that excess Cu triggered pyroptosis (IL-18, NLRP3, GSDMD, Caspase-1), necrosis (MLKL, Caspase-7, Caspase-8) and apoptosis (Bcl-2, Cleaved-Caspase-9/Caspase-9, Cleaved-Caspase-9/Caspase-9), ultimately resulting in PANoptosis in the chicken kidney. Furthermore, the bioinformatics analysis indicated a correlation between lipid metabolism and PANoptosis-related markers. The aforementioned results indicate that Cu-induced disruption to lipid metabolism may contribute to the process of PANoptosis in broiler kidneys.