1,6-Dihydroxynaphthalene as a potential environmental obesogen induces lipid accumulation and liver developmental defects in zebrafish.

1,6-Dihydroxynaphthalene (1,6-DHN), a key dye intermediate and metabolite of polycyclic aromatic hydrocarbons, may pose environmental endocrine-disrupting risks. However, its toxicological effects remain poorly understood. Using zebrafish as a model, this study systematically examined the impact of 1,6-DHN on liver development in larvae. Exposure to 1,6-DHN significantly inhibited liver growth, induced abnormal lipid and glycogen accumulation, and promoted excessive reactive oxygen species (ROS) production, leading to lipid peroxidation. Transcriptomic analysis revealed disrupted expression of key PPAR signaling pathway genes (pparγ, LXR, RXR, SREBP), contributing to metabolic dysregulation. Moreover, 1,6-DHN upregulated pro-apoptotic genes p53 and bax, triggering hepatocyte apoptosis. Knockdown of p53 expression partially alleviated liver toxicity, confirming the pivotal role of the p53 pathway. These findings provide the first evidence that 1,6-DHN impairs zebrafish liver development through oxidative stress, lipid metabolism disruption, and apoptosis, suggesting its potential as an environmental obesogen. Given its widespread industrial use, the ecological and human health risks of 1,6-DHN warrant further attention.