Di(2-ethylhexyl) phthalate exposure under high-fat diet conditions alters oxidative stress, lipogenesis, and adipogenesis in rat liver and adipose tissues.

Environmental factors such as diet and Di(2-ethylhexyl) phthalate (DEHP) have individually been shown to affect lipid metabolism. However, whether DEHP exposure further aggravates metabolic disturbances under high-fat (HF) diet conditions remains insufficiently understood. In this study, we investigated oxidative stress-related responses, lipogenesis- and adipogenesis-related alterations, and liver-adipose tissue changes in rats exposed to DEHP in this model. Metabolic alterations were evaluated by analyzing serum lipid levels, liver and adipose tissue morphology, mRNA expression, enzyme activities, antioxidative defense, and oxidative damage. DEHP-treated HF diet-fed rats showed histopathological alterations in rat liver and adipose tissues. Representative quantitative changes included a 2.64-fold increase in serum TG levels in the DEHP-0.5 group, a 16.64% increase in the liver/body weight ratio in the DEHP-100 group, and a 4.36-fold increase in hepatic MDA levels in the DEHP-100 group. In addition, DEHP exposure altered oxidative stress-related markers and the mRNA expression of lipid metabolism-related genes, such as LDLR. These findings suggest that liver-adipose tissue crosstalk may be involved in metabolic disturbances associated with DEHP exposure in HF diet-fed rats. Further studies including DEHP-only groups under regular diet conditions are needed to clarify the independent effects of DEHP and its potential interactions with dietary fat.