The effects of di 2-ethyl hexyl phthalate (DEHP) on cellular lipid accumulation in HepG2 cells and its potential mechanisms in the molecular level

Toxicol Mech Methods. 2017 May;27(4):245-252. doi: 10.1080/15376516.2016.1273427. Epub 2017 Feb 1.


Diethylhexyl phthalate (DEHP) is suspected to be an inevitable factor related to metabolic disease. Our previous study demonstrated that excess DEHP could exacerbate non-alcoholic fatty liver disease (NAFLD) in SD rats. Addressing the terra incognita in DEHP-induced metabolic dysfunction, this study used HepG2 cells to investigate the potential mechanisms involved in DEHP-induced toxicity in vitro. The cells were established lipid overload model with oleic acid and BSA, then exposed to different concentrations (5, 10, 25, 50, 100 μmol/l DEHP) of DEHP for further analysis. The Oil Red O staining results showed that DEHP could promote lipid accumulation in cells. The level of superoxide dismutase (SOD) and malondialdehyde (MDA) changed suggested the balance of oxidative stress was disrupted. Additionally, western blot analysis showed that DEHP could promote the expression of peroxisome proliferator-activated receptor α (PPARα) and sterol regulatory element-binding protein 1c (SREBP-1c). By quantifying the expressions of the two proteins, it is of interest to determine that DEHP could promote lipid accumulation in hepatocytes via activating the SREBP-1c and PPARα-signaling pathway.

Keywords: DEHP; PPAR; ROS; SREBP; lipid accumulation.

MeSH terms

  • Cell Culture Techniques
  • Diethylhexyl Phthalate / toxicity*
  • Dose-Response Relationship, Drug
  • Hep G2 Cells
  • Humans
  • Lipid Metabolism / drug effects*
  • Malondialdehyde / metabolism
  • Microscopy, Confocal
  • Oleic Acid / metabolism*
  • Oxidative Stress / drug effects
  • PPAR alpha / metabolism
  • Plasticizers / toxicity*
  • Sterol Regulatory Element Binding Protein 1 / metabolism
  • Superoxide Dismutase / metabolism


  • PPAR alpha
  • Plasticizers
  • Sterol Regulatory Element Binding Protein 1
  • Oleic Acid
  • Malondialdehyde
  • Diethylhexyl Phthalate
  • Superoxide Dismutase