Exposure of adipocytes to bisphenol-A in vitro interferes with insulin action without enhancing adipogenesis

PLoS One. 2018 Aug 22;13(8):e0201122. doi: 10.1371/journal.pone.0201122. eCollection 2018.


Bisphenol-A (BPA) is a lipophilic compound widely used in the manufacture of plastic items and thought to play a role in the growing obesity epidemic. Recent publications suggest that BPA may have a pro-adipogenic effect. Here we explore the effect of low, but environmentally relevant, concentrations of BPA on adipogenesis using a variety of cellular models. Mouse 3T3-L1, C3H10T1/2 and human adipose-derived stromal cells (hADSCs) were cultured with BPA concentrations ranging from 0.1nM to 100μM. We failed to observe positive effects on differentiation at any dose or in any model. 3T3-L1 adipocytes differentiated with high concentrations of BPA showed decreased mRNA expression of several adipocyte markers. Mature adipocytes differentiated in the presence of BPA were insulin resistant, with an approximate 25% reduction in insulin-stimulated glucose uptake. This was accompanied by a significant decrease in insulin-stimulated Akt phosphorylation, and an increase in mRNA levels of inflammatory markers (i.e. IL-6, TNFα). In conclusion, low, but environmentally relevant, doses of BPA may contribute to the development of a chronic, low-grade inflammatory state in exposed adipocytes, which in turn may affect adipose tissue insulin sensitivity, independent of adipogenesis. These studies suggest an alternative mechanism by which BPA may contribute to the development of obesity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3-L1 Cells
  • Adipocytes / drug effects*
  • Adipogenesis / drug effects*
  • Adipose Tissue / drug effects
  • Animals
  • Benzhydryl Compounds / adverse effects*
  • Cell Differentiation / drug effects
  • Cell Line / drug effects
  • Cells, Cultured
  • Glucose / metabolism
  • Humans
  • Insulin / metabolism
  • Insulin Resistance
  • Mice
  • Obesity / metabolism
  • Phenols / adverse effects*


  • Benzhydryl Compounds
  • Insulin
  • Phenols
  • Glucose
  • bisphenol A