Exposure to 6-PPD quinone enhances lipid accumulation through activating metabolic sensors of SBP-1 and MDT-15 in Caenorhabditis elegans*

Although it has been shown that exposure to 6-PPDQ can cause toxicity on environmental organisms, its possible effects on metabolic state remain largely unclear. We here determined the effect of 6-PPDQ exposure on lipid accumulation in Caenorhabditis elegans. We observed increase in triglyceride content, enhancement in lipid accumulation, and increase in size of lipid droplets in 6-PPDQ (1-10 & mu;g/L) exposed nematodes. This detected lipid accumulation was associated with both increase in fatty acid synthesis reflected by increased expressions of fasn-1 and pod-2 and inhibition in mitochondrial and peroxisomal fatty acid & beta;-oxidation indicated by decreased expressions of acs-2, ech-2, acs-1, and ech-3. The observed lipid accumulation in 6-PPDQ (1-10 & mu;g/L) exposed nematodes was also related to the increase in synthesis of monounsaturated fatty acylCoAs reflected by altered expressions of fat-5, fat-6, and fat-7. Exposure to 6-PPDQ (1-10 & mu;g/L) further increased expressions of sbp-1 and mdt-15 encoding two metabolic sensors to initiate the lipid accumulation and to regulate the lipid metabolism. Moreover, the observed increase in triglyceride content, enhancement in lipid accumulation, and alterations in fasn-1, pod-2, acs-2, and fat-5 expressions in 6-PPDQ exposed nematodes were obviously inhibited by sbp-1 and mdt-15 RNAi. Our observations demonstrated the risk of 6-PPDQ at environmentally relevant concentration in affecting lipid metabolic state in organisms.

Automated summary

Exposure to 6-PPDQ leads to lipid accumulation and inhibition of fatty acid β-oxidation in Caenorhabditis elegans. This lipid accumulation is associated with increased fatty acid synthesis and increased synthesis of monounsaturated fatty acylCoAs. Additionally, metabolic sensors sbp-1 and mdt-15 are upregulated in response to 6-PPDQ exposure.