Effects of Bisphenol S on hypothalamic neuropeptides regulating feeding behavior and apelin/APJ system in mice

Ecotoxicol Environ Saf. 2018 Oct;161:459-466. doi: 10.1016/j.ecoenv.2018.06.001. Epub 2018 Jun 14.


Since 2010, Bisphenol A (BPA), an endocrine disruptor has been restricted and replaced by analogues like Bisphenol S (BPS). However, little is known about BPS effects and growing concern have suspected the "BPA-free" Label. Several recent studies suggest that BPS is associated with increased risk of diabetes and obesity. However, the underlying mechanisms remain unidentified. The current study investigates investigate BPS effects on hypothalamic neuropeptides regulating feeding behavior, either orexigenic or anorexigenic in Swiss Albino mice. We also studied the effect of BPS on the apelinergic system (apelin/apelin receptor (APJ)) as an original physiological system with pleiotropic actions. Bisphenol S at 25, 50, 100 µg/kg was administered to mice in water drink for 10 weeks started after weaning. Our results showed that BPS exposure alters orexigenic hypothalamic neuropeptide (AgRP) regulating feeding behavior but not anorexigenic neuropeptides (POMC, CART). Such orexigenic alterations may underlay appetite disorders leading to a concomitant food intake and body weight gain increase. In addition, data show that BPS affects the hypothalamic apelinergic system. We found a significant decrease in APJ mRNA but not in apelin expression. Based on hypothalamic APJ distribution, we suggested a potent specific physiological alteration of this receptor in mediating neuroendocrine responses in hypothalamus. Thus, our findings provide that BPS exposure could contribute to the development of obesity and metabolic disorders.

Keywords: Bisphenol S; Food intake; Hypothalamus; Neurotoxicity; Orexigenic/anorexigenic neuropeptides.

MeSH terms

  • Animals
  • Apelin / metabolism*
  • Apelin Receptors / metabolism
  • Benzhydryl Compounds
  • Body Weight
  • Eating / drug effects*
  • Feeding Behavior / drug effects
  • Hypothalamus / drug effects*
  • Hypothalamus / metabolism
  • Male
  • Mice
  • Nerve Tissue Proteins / metabolism
  • Neuropeptides / genetics
  • Neuropeptides / metabolism*
  • Obesity / chemically induced
  • Phenols / toxicity*
  • Pro-Opiomelanocortin / metabolism
  • RNA, Messenger / metabolism
  • Sulfones / toxicity*
  • Weight Gain


  • Apelin
  • Apelin Receptors
  • Aplnr protein, mouse
  • Benzhydryl Compounds
  • Nerve Tissue Proteins
  • Neuropeptides
  • Phenols
  • RNA, Messenger
  • Sulfones
  • cocaine- and amphetamine-regulated transcript protein
  • Pro-Opiomelanocortin
  • bis(4-hydroxyphenyl)sulfone
  • bisphenol A