Maternal Exposure to Low-Dose BDE-47 Induced Weight Gain and Impaired Insulin Sensitivity in the Offspring

Int J Mol Sci. 2024 Aug 7;25(16):8620. doi: 10.3390/ijms25168620.

Abstract

Polybrominated diphenyl ethers (PBDEs), commonly used as synthetic flame retardants, are present in a variety of consumer products, including electronics, polyurethane foams, textiles, and building materials. Initial evidence from epidemiological and experimental studies suggests that maternal PBDE exposure may be associated with a higher BMI in children, with disturbance of energy metabolism and an increased risk of Type 2 diabetes. However, the causality between early exposure to real-life PBDE concentrations and increased weight as well as mechanisms underlying impaired metabolic pathways in the offspring remain elusive. Here, using a mouse model we examined the effect of maternal exposure to 2,2',4,4'-tetrabrominated diphenyl ether (BDE-47), the most abundant congener in human samples, on offspring weight gain and energy homeostasis using a mouse model. Maternal exposure to BDE-47 at low dose resulted in weight gain in female offspring together with an impaired glucose and insulin tolerance in both female and male mice. In vitro and in vivo data suggest increased adipogenesis induced by BDE-47, possibly mediated by DNA hypermethylation. Furthermore, mRNA data suggest that neuronal dysregulation of energy homeostasis, driven via a disturbed leptin signaling may contribute to the observed weight gain as well as impaired insulin and glucose tolerance.

Keywords: BDE-47; epigenetics; leptin; metabolism; overweight; pregnancy; sex-specific effect.

MeSH terms

  • Adipogenesis / drug effects
  • Animals
  • DNA Methylation / drug effects
  • Energy Metabolism / drug effects
  • Female
  • Flame Retardants / adverse effects
  • Flame Retardants / toxicity
  • Halogenated Diphenyl Ethers* / toxicity
  • Insulin Resistance*
  • Leptin / metabolism
  • Male
  • Maternal Exposure* / adverse effects
  • Mice
  • Pregnancy
  • Prenatal Exposure Delayed Effects* / metabolism
  • Weight Gain* / drug effects

Substances

  • Halogenated Diphenyl Ethers
  • 2,2',4,4'-tetrabromodiphenyl ether
  • Leptin
  • Flame Retardants

Grants and funding

This work was supported by institutional funding from the Helmholtz Centre for Environmental Research—UFZ. The graphical abstract was created with BioRender.com.