6-PPD quinone causes lipid accumulation across multiple generations differentially affected by metabolic sensors and components of COMPASS complex in Caenorhabditis elegans

The toxicity of 6-PPD quinone (6-PPDQ) has been frequently detected. However, the possible transgenerational effects of 6-PPDQ remain largely unclear. Due to short life cycle and high sensitivity to environmental exposure, Caenorhabditis elegans is useful for study of transgenerational toxicology. In C. elegans, we observed the transgenerational increase in lipid accumulation after parental generation (P0-G) exposure to 6-PPDQ at 0.1-10 μg/L belong to environmentally relevant concentrations. Accompanied with this, transgenerational increase in expressions of genes governing fatty acid synthesis and monounsaturated fatty acyl-CoAs synthesis and decrease in genes governing fatty acid β-oxidation were induced by 6-PPDQ exposure. Moreover, 6-PPDQ exposure at P0-G caused transgenerational activation of mdt-15 and sbp-1 encoding lipid metabolic sensors. Meanwhile, exposure to 6-PPDQ induced transgenerational activation of set-2 and inhibition in rbr-2, two genes encoding components of COMPASS complex. The 6-PPDQ induced transgenerational lipid accumulation could be strengthened by RNAi of set-2 and suppressed by RNA interference (RNAi) of rbr-2. Additionally, 6-PPDQ induced transgenerational neurotoxicity could be increased by RNAi of mdt-15, sbp-1, and rbr-2, and inhibited by RNAi of set-2. Therefore, our results demonstrated the possibility in resulting in transgenerational lipid accumulation by exposure to 6-PPDQ.