Bisphenol AF promotes inflammation in human white adipocytes

Am J Physiol Cell Physiol. 2020 Jan 1;318(1):C63-C72. doi: 10.1152/ajpcell.00175.2019. Epub 2019 Oct 9.


Endocrine-disrupting chemicals interact with transcription factors essential for adipocyte differentiation. Exposure to endocrine-disrupting chemicals corresponds with elevated risks of obesity, but the effects of these compounds on human cells remain largely undefined. Widespread use of bisphenol AF (BPAF) as a bisphenol A (BPA) alternative in the plastics industry presents unknown health risks. To this end, we discovered that BPAF interferes with the metabolic function of mature human adipocytes. Although 4-day exposures to BPAF accelerated adipocyte differentiation, we observed no effect on mature fat cell marker genes. Additional gene and protein expression analysis showed that BPAF treatment during human adipocyte differentiation failed to suppress the proinflammatory transcription factor STAT1. Microscopy and respirometry experiments demonstrated that BPAF impaired mitochondrial function and structure. To test the hypothesis that BPAF fosters vulnerabilities to STAT1 activation, we treated mature adipocytes previously exposed to BPAF with interferon-γ (IFNγ). BPAF increased IFNγ activation of STAT1 and exposed mitochondrial vulnerabilities that disrupt adipocyte lipid and carbohydrate metabolism. Collectively, our data establish that BPAF activates inflammatory signaling pathways that degrade metabolic activity in human adipocytes. These findings suggest how the BPA alternative BPAF contributes to metabolic changes that correspond with obesity.

Keywords: PPARγ; adipocyte; inflammation; metabolism; transcription.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes, White / drug effects*
  • Adipocytes, White / metabolism
  • Adipocytes, White / pathology
  • Adipogenesis / drug effects
  • Adipose Tissue, White / drug effects*
  • Adipose Tissue, White / metabolism
  • Adipose Tissue, White / pathology
  • Benzhydryl Compounds / toxicity*
  • Cells, Cultured
  • Endocrine Disruptors / toxicity*
  • Energy Metabolism / drug effects*
  • Gene Expression Regulation
  • Humans
  • Interferon-gamma / pharmacology
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • Mitochondria / pathology
  • PPAR gamma / genetics
  • PPAR gamma / metabolism
  • Panniculitis / chemically induced*
  • Panniculitis / metabolism
  • Panniculitis / pathology
  • Phenols / toxicity*
  • STAT1 Transcription Factor / genetics
  • STAT1 Transcription Factor / metabolism
  • Signal Transduction


  • Benzhydryl Compounds
  • Endocrine Disruptors
  • IFNG protein, human
  • PPAR gamma
  • PPARG protein, human
  • Phenols
  • STAT1 Transcription Factor
  • STAT1 protein, human
  • Interferon-gamma
  • 4,4'-hexafluorisopropylidene diphenol