Impairment of bisphenol F on the glucose metabolism of zebrafish larvae

Ecotoxicol Environ Saf. 2018 Dec 15;165:386-392. doi: 10.1016/j.ecoenv.2018.09.017. Epub 2018 Sep 12.

Abstract

Bisphenol F (BPF) is a substitute of bisphenol A in the production of epoxy resin and polycarbonate. Its extensive use in consumer products leads to a wide human exposure at high levels. Although the adverse effects of BPF on animal health are of increasing public concern, its risks on systematic glucose metabolism and blood glucose concentrations still remain largely unknown. Using zebrafish larvae as the model animal, we investigated the disturbance of BPF exposure on glucose metabolism and the underlying mechanisms. Zebrafish larvae at 96 h post fertilization were exposed to 0.1, 1, 10, and 100 μg/L of BPF for 48 h. Compared with the control group, glucose levels of larvae increased significantly in the 10 and 100 μg/L exposure groups, which are associated with enhancement of gluconeogenesis and suppression of glycolysis induced by high doses of BPF. Additionally, both mRNA expressions and protein levels of insulin increased significantly in the 10 and 100 μg/L exposure groups, while transcription levels of genes encoding insulin receptor substrates decreased significantly in these groups, indicating a possibly decreased insulin sensitivity due to impairment of insulin signaling transduction downstream of insulin receptor. Further, compared with BPF alone, co-exposure of larvae to BPF and rosiglitazone, an insulin sensitizer, significantly attenuates increases in both glucose levels and mRNA expressions of a key gluconeogenesis enzyme. Our data therefore indicate impairing insulin signaling transduction may be the main mechanism through which BPF disrupts glucose metabolism and induces hyperglycemia. Results of the present study inform the health risk assessment of BPF and also suggest the use of zebrafish larvae in large-scale screening of chemicals with possible glucose metabolism disturbing effect.

Keywords: Animal model; Bisphenol F; Glucose metabolism; Insulin; Zebrafish larvae.

MeSH terms

  • Animals
  • Benzhydryl Compounds / pharmacology*
  • Gluconeogenesis / drug effects
  • Glucose / metabolism*
  • Glycolysis / drug effects
  • Hypoglycemic Agents / pharmacology
  • Insulin / genetics
  • Insulin / metabolism
  • Larva / drug effects
  • Larva / metabolism*
  • Phenols / pharmacology*
  • RNA, Messenger / metabolism
  • Receptor, Insulin / genetics
  • Rosiglitazone / pharmacology
  • Signal Transduction / drug effects*
  • Zebrafish / metabolism*

Substances

  • Benzhydryl Compounds
  • Hypoglycemic Agents
  • Insulin
  • Phenols
  • RNA, Messenger
  • bisphenol F
  • Rosiglitazone
  • Receptor, Insulin
  • Glucose