Objective Phthalates is a kind of recognized environmental endocrine disruptors, and its universal applications as a plasticizer allow various exposure pathways and have raised increasing health concerns. Although available studies have reported its hepatotoxicity, the specifc mechanism requires further investgaton. This study is designed to observe the effects of mono(2-ethylhexyl) phthalate (MEHP) on triglyceride (TG) synthesis in HepG2 cells, and to further assess the effects of MEHP on lipid metabolism.
Methods HepG2 cells were treated with various concentratons of MEHP (0, 0.8, 4.0, 20.0, and 100.0 μmol/L) and 0.5 mmol/L oleic acid (OA, positve control) for 24 h and 48 h, respectvely, and detected for intra-and extra-hepatocellular TG contents by chemical-enzymatc method. HepG2 cells were treated with various concentratons of MEHP (0, 0.01, 1.0, 10.0, and 100.0μmol/L) and 1 mmol/L OA (positve control) for 6 h, 24 h, and 48 h, respectvely, and measured for the mRNA expression levels of genes related to TG synthesis by real-tme quanttatve PCR, including GPAM, AGPAT2, LPIN2, and DGAT2.
Results Compared with the negative control group, after 24 h treatment, only the 0.5 μmol/L OA signifcantly increased the extra-hepatocellular TG contents, and the 20-100 μmol/L MEHP and the 0.5 μmol/L OA signifcantly increased the intra-hepatocellular TG contents (P < 0.05); afer 48 h treatment, the 100.0 μmol/L MEHP and the 0.5 μmol/L OA signifcantly increased the extra-hepatocellular TG contents, and the 20.0-100.0 μmol/L MEHP and 0.5 μmol/L OA signifcantly increased the intra-hepatocellular TG contents (P < 0.05). Compared with the negatve control group, the mRNA expression levels of GPAM were increased in HepG2 cells treated with 1.0-100.0μmol/L MEHP for 6h, 100.0μmol/L MEHP for 24h, and 10.0-100.0μmol/L MEHP for 48h (P < 0.05); the mRNA expression levels of AGPAT2 were increased afer exposure to all designed concentratons of MEHP for 6, 24, and 48 h (P < 0.05); the mRNA expression levels of LPIN2 were increased afer 10.0-100.0 μmol/L MEHP exposure for 6, 24, and 48 h (P < 0.05); the mRNA expression levels of DGAT2 were increased afer being treated with 10.0-100.0μmol/L MEHP for 6h, 100.0μmol/L MEHP for 24h, and 0.01-100.0μmol/L MEHP for 48h (P < 0.05).
Conclusion High concentratons of MEHP can increase TG contents in HepG2 cells, leading to lipid metabolism disorder.
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