Arsenic induces hepatic lipid accumulation associated with DNA methylation alterations and oxidative stress in marine medaka (Oryzias melastigma).

Arsenic (As) contamination is a global environmental concern, but its toxicity and mechanisms on marine organisms remain largely unknown. In this study, marine medaka (Oryzias melastigma) were exposed to dietary arsenate (AsV) at 0, 100, and 1000 μg/g for 28 days, and primary hepatocyte cultures were established to investigate the underlying mechanisms. The results showed that AsV induced significant and dose‑dependent lipid accumulation both in vivo and in vitro, following the internal arsenic burden. The transcription of lipogenic genes was upregulated, and the transcription of lipolytic genes was downregulated after AsV exposure. AsV reduced the level of SAM, suppressed transcription of dnmt1 and tet3, and induced hypomethylation of the ppargc1b promoter. Correspondingly, AsV upregulated the transcription of ppargc1b, which might modulate downstream genes of the PPAR signaling pathway and impaired lipid metabolism. In addition, the redox cycle of arsenic triggered oxidative stress and endoplasmic reticulum stress. The ROS scavengers GSH and NAC significantly alleviated arsenic‑induced lipid accumulation and aberrant gene expression, whereas the ER stress PBA inhibitor showed no protective effect. Our results demonstrated that AsV induced lipid accumulation associated with DNA methylation alterations and oxidative stress, providing insights into arsenic lipotoxicity and ecological risk assessment in marine environments.