Bisphenol F and bisphenol S promote lipid accumulation and adipogenesis in human adipose-derived stem cells

Food Chem Toxicol. 2021 Jun:152:112216. doi: 10.1016/j.fct.2021.112216. Epub 2021 Apr 15.

Abstract

Bisphenol F (BPF) and bisphenol S (BPS) are increasingly used as substitutes for bisphenol A (BPA), an endocrine disrupting chemical (EDC) with obesogenic activity. We investigated the in vitro effects of BPS and BPF on the adipogenesis of human adipose-derived stem cells (hASCs) exposed to different doses (0.01, 0.1, 1, 10 and 25 μM), stopping the adipogenic process at 7 or 14 days. Intracellular lipid accumulation was quantified by the Oil Red O assay, gene expression of peroxisome proliferator-activated receptor gamma (PPARγ), CCAT/enhancer-binding protein (C/EBPα), lipoprotein-lipase (LPL) and fatty acid binding protein 4 (FABP4), by quantitative real-time polymerase chain reaction (qRT-PCR) and protein levels by Western Blot. hASCs with BPF or BPS produced a linear dose-response increase in intracellular lipid accumulation and in gene expression of the adipogenic markers, confirmed by protein levels. Co-treatment ICI 182,780 significantly inhibited BPF- but not BPS-induced lipid accumulation. Given the affinity of bisphenols for diverse nuclear receptors, their obesogenic effects may result from a combination of pathways rather than a single mechanism. Further research is warranted on the manner in which chemicals interfere with adipogenic differentiation. To our best knowledge, this report shows for the first time the obesogenic potential of BPF in hASCs.

Keywords: Adipogenesis; Bisphenol A (BPA); Bisphenol F (BPF); Bisphenol S (BPS); Endocrine disruptors; Obesity.

MeSH terms

  • Adipogenesis / drug effects*
  • Benzhydryl Compounds / toxicity*
  • CCAAT-Enhancer-Binding Protein-alpha / metabolism
  • Cell Differentiation / drug effects*
  • Dose-Response Relationship, Drug
  • Fatty Acid-Binding Proteins / metabolism
  • Gene Expression / drug effects
  • Humans
  • Lipoprotein Lipase / metabolism
  • Mesenchymal Stem Cells / drug effects*
  • PPAR gamma / metabolism
  • Phenols / toxicity*
  • Sulfones / toxicity*

Substances

  • Benzhydryl Compounds
  • CCAAT-Enhancer-Binding Protein-alpha
  • FABP4 protein, human
  • Fatty Acid-Binding Proteins
  • PPAR gamma
  • Phenols
  • Sulfones
  • bisphenol F
  • bis(4-hydroxyphenyl)sulfone
  • LPL protein, human
  • Lipoprotein Lipase