Tetra methyl bisphenol F: another potential obesogen

Misha Singh; Jennifer Crosthwait; Alexander Sorisky; Ella Atlas

doi:10.1038/s41366-024-01496-5

Tetra methyl bisphenol F: another potential obesogen

Int J Obes (Lond). 2024 Feb 22. doi: 10.1038/s41366-024-01496-5. Online ahead of print.

Authors

Misha Singh¹, Jennifer Crosthwait¹, Alexander Sorisky^{2

3

4}, Ella Atlas^{5

6}

Affiliations

¹ Environmental Health Science and Research Bureau (EHSRB), Health Canada, 251 Sir Frederick Banting Driveway, Ottawa, ON, K1A 0K9, Canada.
² Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON, K1H 8M5, Canada.
³ Department of Medicine, University of Ottawa, Ottawa, ON, Canada.
⁴ Chronic Disease Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada.
⁵ Environmental Health Science and Research Bureau (EHSRB), Health Canada, 251 Sir Frederick Banting Driveway, Ottawa, ON, K1A 0K9, Canada. ella.atlas@hc-sc.gc.ca.
⁶ Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON, K1H 8M5, Canada. ella.atlas@hc-sc.gc.ca.

PMID: 38388800
DOI: 10.1038/s41366-024-01496-5

Abstract

Background/objectives: Obesity and its associated metabolic diseases are increasing globally. Sedentary lifestyle, high caloric diet, and genetic predisposition are known to contribute to the onset of obesity. It is increasingly recognized that exposure to environmental chemicals such as Bisphenol A (BPA) may also play a significant role. BPA has been correlated with an array of adverse health effects, including obesity and metabolic disorders. Due to public concern, manufacturers are replacing BPA with structural analogues for which there is limited toxicological data. The objective of this study was to assess the effects of these BPA analogues on adipogenesis.

Methods: The adipogenic effects of Tetra Methyl Bisphenol F (TMBPF), Bisphenol F (BPF), Bisphenol AP (BPAP), and fluorine-9-bisphenol (BHPF) were evaluated in murine 3T3-L1 cells. The cells were treated with BPA and its analogues at concentrations from 0.01 µM to 20 µM, throughout differentiation, in the absence of Dexamethasone (Dex). Lipid accumulation, mRNA and protein levels of adipogenic markers was assessed.

Results: We found that TMBPF, BPF and BPA increased 3T3-L1 lipid accumulation and the expression levels of adipogenic markers lipoprotein lipase (Lpl), fatty acid binding protein 4 (Fabp4) and perilipin (Plin) (1-20 µM; p < 0.05), whereas BHPF and BPAP had no effect in this model. Further, TMBPF induced adipogenesis to a greater extent than all the other chemicals including BPA (1-20 µM; p < 0.05). The effect mediated by TMBPF on expression levels of Fabp4, but not Plin, is likely mediated via peroxisome proliferator-activated receptor (PPAR) γ activation.

Conclusions: Of the BPA analogues tested, BPF was most similar to BPA in its effects, while TMBPF was most adipogenic. In addition, TMBPF is likely a PPARγ agonist, it is likely an obesogenic chemical and may be a metabolic disruptor.