Organophosphate ester cresyl diphenyl phosphate disrupts lipid homeostasis in zebrafish embryos

As a new class of organophosphate ester, cresyl diphenyl phosphate (CDP) has been widely monitored in environmental matrices and human samples, nonetheless, its toxicity is not fully understood. Here we described an in-depth analysis of the disruptions in lipid homeostasis of zebrafish following exposure to CDP concentrations ranging from 2.0 to 313.0 μg/L. Nile red staining revealed significant alterations in lipid contents in 72 hpf zebrafish embryos at CDP concentrations of 5.3 μg/L and above. Lipidomic analysis unveiled substantial disruptions in lipid homeostasis. Notably, disruptive effects were detected in various lipid classes, including phospholipids (i.e. cardiolipin, lysophosphatidylcholine, and phosphatidylethanolamine), glycerolipids (triglycerides), and fatty acids (fatty acids (FA) and wax esters (WE)). These alterations were further supported by transcriptional changes, with remarkable shifts observed in genes associated with lipid synthesis, transport, and metabolism, encompassing phospholipids, glycerolipids, fatty acids, and sphingolipids. Furthermore, CDP exposure elicited a significant elevation in ATP content and swimming activity in embryos, signifying perturbed energy homeostasis. Taken together, the present findings underscore the disruptive effects of CDP on lipid homeostasis, thereby providing novel insights essential for advancing the health risk assessment of organophosphate flame retardants.