Di(2‐Ethylhexyl) Phthalate Exposure Alters Hepatic Lipid Metabolism in Male SAMP8 Aged Mice

As a widespread environmental pollutant, di(2-ethylhexyl) phthalate (DEHP) mainly leaches from plastic products into food and is ultimately absorbed by living organisms. DEHP and its metabolites pose potential threats to human and animal health, particularly through metabolic disorders. While existing studies have explored DEHP's impact on lipid metabolism, investigations in aged mice remain scarce. This study aimed to investigate the effects of DEHP exposure on hepatic lipid metabolism and gut microbiota in mice. Male senescence-accelerated (SAMP8) were orally exposed to DEHP (0, 0.2, and 200 mg/kg/day) for 5 weeks. Results showed that DEHP exposure significantly interfered with hepatic lipid profiles, leading to elevated liver triglyceride (TG) levels. Furthermore, DEHP exposure influenced the alpha and beta diversity of the gut microbiota. An increase in the Firmicutes/Bacteroidota ratio suggests that DEHP exposure causes changes in the composition of the gut microbiota. The association between hepatic lipidomics and gut microbiota showed a positive correlation between specific genera like Alloprevotella and various hepatic lipids. Finally, we further clarified the molecular mechanism of increased hepatic TG, identifying elevated fatty acid synthase FASN as a key factor. In summary, these results suggest that DEHP exposure disrupts lipid metabolism in the liver, possibly mediated by gut microbiota dysbiosis.