Parental sodium benzoate diet induces fat accumulation in offspring via histone H3K9me3 and SKN-1/Nrf2.

Sodium benzoate is a commonly used food preservative and chemical additive with well-established antimicrobial and antifungal activities, and is widely applied in the food, cosmetic, and pharmaceutical industries. Despite its extensive use, increasing evidence has raised concerns regarding its potential adverse effects on metabolic homeostasis, including the induction of oxidative stress, hepatic inflammation, lipid accumulation, and reduced lifespan. However, whether sodium benzoate-induced obesity phenotypes can be transmitted to subsequent generations via epigenetic mechanisms remains largely unexplored. In this study, we used Caenorhabditis elegans as a model organism to investigate whether the high-lipid phenotype induced by sodium benzoate could be inherited epigenetically by offspring. Our results demonstrated that exposure to sodium benzoate led to a high-lipid phenotype that persisted across multiple generations through epigenetic inheritance. Mechanistically, the transcription factor SKN-1 functioned not only as an effector regulating lipid metabolism but also as a key mediator transmitting epigenetic information to progeny. Furthermore, we identified histone H3 lysine 9 trimethylation (H3K9me3) as a critical epigenetic modification underlying this transgenerational effect. Collectively, these findings indicate that sodium benzoate induces heritable lipid accumulation through the SKN-1/Nrf2 signaling pathway, accompanied by a reduction in H3K9me3 levels.