Combined Exposure to Fructose and Bisphenol A Exacerbates Abnormal Lipid Metabolism in Liver of Developmental Male Rats

Int J Environ Res Public Health. 2019 Oct 28;16(21):4152. doi: 10.3390/ijerph16214152.


The aim of this study was to investigate whether combined exposure to fructose and bisphenol A (BPA) has a synergistic effect on abnormal lipid metabolism in the liver of developmental male rats and its possible mechanism. Fifty weaned male Wistar rats were divided into five groups: the control, 13% fructose, 20% fructose, 1 µg/mL BPA, and 13% fructose + 1 µg/mL BPA (combined exposure). Rats were exposed to fructose and/or BPA through drinking water for eight weeks. Genes or proteins regulating lipid metabolism include sterol regulatory element binding protein 1 (SREBP1), adipose triglyceride lipase (ATGL), hormone sensitive lipase (HSL), acetyl-CoA carboxylase 1 (ACC1), fatty acid synthase (FAS), zinc α 2 glycoprotein (ZAG) and estrogen receptor α (ERα), and the expression of proteins regulating inflammatory response, such as TLR4 and NF-κB, were determined. Serum total cholesterol (T-CHO), triglyceride (TG), low, high density lipoprotein cholesterol (LDL-C, HDL-C), blood glucose, insulin, IL-17 and TNF-α levels were also measured. Liver tissue morphology was observed by H&E staining. The results showed that the levels of gene and protein catalyzing lipogenesis were increased (SREBP1, ACC1 and FAS), while those catalyzing lipolysis were decreased (ATGL, HSL and ZAG), accompanied by dyslipidemia, insulin resistance and hepatic fat accumulation, and there were higher expression of TLR4 and NF-κB protein and lower expression of ERα protein in liver, and increased serum IL-17 and TNF-α levels in fructose and/or BPA exposed rats compared with controls. Moreover, the above indicators were more serious in combined exposure group than in single exposure group. Therefore, abnormal lipid metabolism in the liver of developmental rats could be exacerbated by combined exposed to fructose and BPA.

Keywords: bisphenol A; fructose; inflammatory response; lipid metabolism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzhydryl Compounds / administration & dosage
  • Benzhydryl Compounds / adverse effects*
  • Dose-Response Relationship, Drug
  • Dyslipidemias / chemically induced
  • Fructose / administration & dosage
  • Fructose / adverse effects*
  • Inflammation Mediators / metabolism
  • Insulin Resistance / physiology
  • Lipid Metabolism / drug effects*
  • Lipolysis / drug effects
  • Liver / drug effects*
  • Male
  • Phenols / administration & dosage
  • Phenols / adverse effects*
  • Rats
  • Rats, Wistar


  • Benzhydryl Compounds
  • Inflammation Mediators
  • Phenols
  • Fructose
  • bisphenol A