Environmentally Relevant Dose of Bisphenol A Does Not Affect Lipid Metabolism and Has No Synergetic or Antagonistic Effects on Genistein's Beneficial Roles on Lipid Metabolism

PLoS One. 2016 May 12;11(5):e0155352. doi: 10.1371/journal.pone.0155352. eCollection 2016.


Both bisphenol A (BPA, an endocrine disrupting chemicals) and genistein (a phytoestrogen mainly derived from leguminosae) are able to bind to estrogen receptors, but they are considered to have different effects on metabolic syndrome, surprisingly. We here investigate the effects of an environmentally relevant dose of BPA alone and the combined effects with genistein on lipid metabolism in rats. Eight groups of adult male Wistar rats, fed with either standard chow diet or high-fat diet, were treated with BPA (50μg/kg/day), genistein (10mg/kg/day), and BPA plus genistein for 35 weeks, respectively. Metabolic parameters in serum and liver were determined; the hematoxylin/eosin and oil Red O staining were used to observe liver histologically; gene expressions related to hepatic lipid metabolism were analyzed by Real-time PCR; protein expressions of PPARγ, PPARα and LC3 in liver were analyzed by western blotting. No difference of body weight gain, total energy intake, liver weight/body weight or body fat percentage in both STD- and HFD-fed sub-groups was observed after treatment with BPA, genistein, or BPA plus genistein (P>0.05). Genistein alleviated lipid metabolism disorder and decreased the mRNA and protein expression of PPARγ (P<0.05), and increased the protein expression of LC3II (P<0.05) in liver of HFD-fed rats. However, BPA treatment had no effect on lipid metabolism in rats alone (P>0.05) or combined with genistein. Our findings suggest that long-term environmentally relevant dose of BPA did not affect lipid metabolism, and had no synergetic or antagonistic roles on genistein's beneficial function on hepatic lipid metabolism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzhydryl Compounds / toxicity*
  • Body Weight / drug effects
  • Diet, High-Fat
  • Energy Intake / drug effects
  • Environmental Pollutants / toxicity*
  • Genistein / pharmacology*
  • Lipid Metabolism / drug effects*
  • Lipids / blood
  • Liver / drug effects
  • Liver / metabolism
  • Male
  • Metabolome / drug effects
  • Organ Size / drug effects
  • Phenols / toxicity*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats, Wistar
  • Real-Time Polymerase Chain Reaction
  • Staining and Labeling


  • Benzhydryl Compounds
  • Environmental Pollutants
  • Lipids
  • Phenols
  • RNA, Messenger
  • Genistein
  • bisphenol A

Grant support

This work was funded by National Natural Science Foundation of China Grant numbers 81172674, 81373007, 81573160, https://isisn.nsfc.gov.cn/egrantindex/funcindex/prjsearch-list); and Specialized Research Fund for the Doctoral Program of Higher Education of China grant number 20110142110022, http://www.cutech.edu.cn/cn/kyjj/gdxxbsdkyjj/A010301index_1.htm). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.