Di-(2-ethylhexyl) phthalate (DEHP), which is widely used as an industrial plasticizer, may cause liver damage. Concomitantly, bad dietary habits can exacerbate the liver burden. In this study, high-fat diet (HFD)-fed rats were treated with DEHP (10, 100, or 300 mg/kg bw) for 5 weeks, and a biochemical method was adopted to detect serum lipid contents. Key metabolic genes and pathological changes were assessed by different methods (RT-PCR, Western Bloting, ELISA and HE staining). The rats which were exposed to DEHP at a dose of 10 mg/kg bw exhibited dyslipidemia and increased transcription of SREBP-1 and its target FAS, thereby prompting de novo lipogenesis, but they did not become obese. Instead, DEHP at a dose of 300 mg/kg bw elevated the levels of AMPK phosphorylation and the mRNA levels of PPAR-α, PGC-1α, CPT-1 and lipin-1 in the liver, which led to fatty acid oxidation. Additionally, DEHP at the highest dose increased the TNF-α mRNA expression in the liver. Based on these findings, we conclude that excess fatty acid oxidation might increase the inflammatory response. No toxic effects on hepatic function were observed. These findings suggest that different doses of DEHP have the potential to disturb hepatic metabolic imbalance in HFD-fed rats.
Keywords: Fatty acid oxidation; High-fat diet; Lipogenesis; Liver.
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