Exposure to 2,4-dichlorophenoxyacetic acid induced PPARβ-dependent disruption of glucose metabolism in HepG2 cells

Environ Sci Pollut Res Int. 2018 Jun;25(17):17050-17057. doi: 10.1007/s11356-018-1921-6. Epub 2018 Apr 9.


2,4-Dichlorophenoxyacetic acid is one of the most widely used herbicides. Its impact on health is increasingly attracting great attentions. This study aimed to investigate the effect of 2,4-dichlorophenoxyacetic acid on glucose metabolism in HepG2 cells and the underlying mechanism. After 24 h exposure to 2,4-dichlorophenoxyacetic acid, glycogen was measured by PAS staining and glucose by ELISA in HepG2 cells. The expression of genes involved in glucose metabolism was measured by real-time PCR, Western blotting, and immunofluorescence. HepG2 cells presented more extracellular glucose consumption and glycogen content after exposed to 2,4-dichlorophenoxyacetic acid. Expression of gluconeogenesis-related genes, FoxO1, and CREB is significantly elevated. Moreover, PPARβ was up-regulated dose-dependently. SiRNA knockdown of PPARβ completely rescued the increase of glycogen accumulation and glucose uptake, and the up-regulation of FOXO1 and CREB expression. Our findings propose novel mechanisms that 2,4-dichlorophenoxyacetic acid causes glucose metabolism dysfunction through PPARβ in HepG2 cells.

Keywords: 2,4-Dichlorophenoxyacetic acid; Glucose metabolism; Hepatocyte; Herbicides; PPARβ.

MeSH terms

  • 2,4-Dichlorophenoxyacetic Acid*
  • Animals
  • Gluconeogenesis
  • Glucose / chemistry
  • Glucose / metabolism*
  • Glycogen / chemistry
  • Glycogen / metabolism*
  • Hep G2 Cells / chemistry
  • Hep G2 Cells / metabolism*
  • Herbicides / chemistry*
  • Herbicides / metabolism
  • Humans
  • PPAR-beta / chemistry*
  • PPAR-beta / metabolism
  • Up-Regulation


  • Herbicides
  • PPAR-beta
  • 2,4-Dichlorophenoxyacetic Acid
  • Glycogen
  • Glucose