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

• DOI: 10.1016/j.fct.2021.112216
• Publication Date: 2021-04-16T05:34:21Z
• Authors: Iris Reina-Pérez; Alicia Olivas-Mar...; Vicente Mustieles; Francisco Javier ...; José Manuel Molin...; Nicolás Olea; Mariana F. Fernández
• Keywords: 0301 basic medicine; Adipogenesis; Dose-Response Relationship, Drug; Gene Expression; Cell Differentiation; Mesenchymal Stem Cells; Fatty Acid-Binding Proteins; 3. Good health; PPAR gamma; Lipoprotein Lipase; 03 medical and health sciences; Phenols; CCAAT-Enhancer-Binding Protein-alpha; Humans; Sulfones; Benzhydryl Compounds

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.