Tetra Methyl Bisphenol F: Another Potential Obesogen

Overview

Journal Int J Obes (Lond)

Specialty Endocrinology

Date 2024 Feb 22

PMID 38388800

Authors

Misha Singh

Jennifer Crosthwait

Alexander Sorisky

Ella Atlas

Affiliations

Soon will be listed here.

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.

References

Mackall J, Student A, Polakis S, Lane M . Induction of lipogenesis during differentiation in a "preadipocyte" cell line. J Biol Chem. 1976; 251(20):6462-4. View

Ozkemahli G, Erkekoglu P, Ercan A, Zeybek N, Yersal N, Kocer-Gumusel B . Effects of single or combined exposure to bisphenol A and mono(2-ethylhexyl)phthalate on oxidant/antioxidant status, endoplasmic reticulum stress, and apoptosis in HepG2 cell line. Environ Sci Pollut Res Int. 2022; 30(5):12189-12206. DOI: 10.1007/s11356-022-22937-6. View

Atawia R, Bunch K, Toque H, Caldwell R, Caldwell R . Mechanisms of obesity-induced metabolic and vascular dysfunctions. Front Biosci (Landmark Ed). 2019; 24(5):890-934. PMC: 6689231. DOI: 10.2741/4758. View

Boden G, Duan X, Homko C, Molina E, Song W, Perez O . Increase in endoplasmic reticulum stress-related proteins and genes in adipose tissue of obese, insulin-resistant individuals. Diabetes. 2008; 57(9):2438-44. PMC: 2518495. DOI: 10.2337/db08-0604. View

Vandenberg L, Colborn T, Hayes T, Heindel J, Jacobs Jr D, Lee D . Hormones and endocrine-disrupting chemicals: low-dose effects and nonmonotonic dose responses. Endocr Rev. 2012; 33(3):378-455. PMC: 3365860. DOI: 10.1210/er.2011-1050. View

Maffini M, Canatsey R . An expanded toxicological profile of tetramethyl bisphenol F (TMBPF), a precursor for a new food-contact metal packaging coating. Food Chem Toxicol. 2019; 135:110889. DOI: 10.1016/j.fct.2019.110889. View

Ahmed S, Atlas E . Bisphenol S- and bisphenol A-induced adipogenesis of murine preadipocytes occurs through direct peroxisome proliferator-activated receptor gamma activation. Int J Obes (Lond). 2016; 40(10):1566-1573. DOI: 10.1038/ijo.2016.95. View

Pantoja C, Huff J, Yamamoto K . Glucocorticoid signaling defines a novel commitment state during adipogenesis in vitro. Mol Biol Cell. 2008; 19(10):4032-41. PMC: 2555927. DOI: 10.1091/mbc.e08-04-0420. View

Prentice K, Saksi J, Hotamisligil G . Adipokine FABP4 integrates energy stores and counterregulatory metabolic responses. J Lipid Res. 2019; 60(4):734-740. PMC: 6446704. DOI: 10.1194/jlr.S091793. View

10.

Boucher J, Boudreau A, Atlas E . Bisphenol A induces differentiation of human preadipocytes in the absence of glucocorticoid and is inhibited by an estrogen-receptor antagonist. Nutr Diabetes. 2014; 4:e102. PMC: 3904083. DOI: 10.1038/nutd.2013.43. View

11.

Angle B, Do R, Ponzi D, Stahlhut R, Drury B, Nagel S . Metabolic disruption in male mice due to fetal exposure to low but not high doses of bisphenol A (BPA): evidence for effects on body weight, food intake, adipocytes, leptin, adiponectin, insulin and glucose regulation. Reprod Toxicol. 2013; 42:256-68. PMC: 3886819. DOI: 10.1016/j.reprotox.2013.07.017. View

12.

Gramec Skledar D, Carino A, Trontelj J, Troberg J, Distrutti E, Marchiano S . Endocrine activities and adipogenic effects of bisphenol AF and its main metabolite. Chemosphere. 2018; 215:870-880. DOI: 10.1016/j.chemosphere.2018.10.129. View

13.

Bishop-Bailey D, Hla T, Warner T . Bisphenol A diglycidyl ether (BADGE) is a PPARgamma agonist in an ECV304 cell line. Br J Pharmacol. 2000; 131(4):651-4. PMC: 1572386. DOI: 10.1038/sj.bjp.0703628. View

14.

Welshons W, Nagel S, Vom Saal F . Large effects from small exposures. III. Endocrine mechanisms mediating effects of bisphenol A at levels of human exposure. Endocrinology. 2006; 147(6 Suppl):S56-69. DOI: 10.1210/en.2005-1159. View

15.

Boucher J, Ahmed S, Atlas E . Bisphenol S Induces Adipogenesis in Primary Human Preadipocytes From Female Donors. Endocrinology. 2016; 157(4):1397-407. DOI: 10.1210/en.2015-1872. View

16.

Lang I, Galloway T, Scarlett A, Henley W, Depledge M, Wallace R . Association of urinary bisphenol A concentration with medical disorders and laboratory abnormalities in adults. JAMA. 2008; 300(11):1303-10. DOI: 10.1001/jama.300.11.1303. View

17.

Edaes F, de Souza C . BPS and BPF are as Carcinogenic as BPA and are Not Viable Alternatives for its Replacement. Endocr Metab Immune Disord Drug Targets. 2022; 22(9):927-934. DOI: 10.2174/1871530322666220316141032. View

18.

Desai M, Ferrini M, Jellyman J, Han G, Ross M . In vivo and in vitro bisphenol A exposure effects on adiposity. J Dev Orig Health Dis. 2018; 9(6):678-687. PMC: 6363869. DOI: 10.1017/S2040174418000600. View

19.

Choi S, Kwon H, Han X, Men X, Choi Y, Jang G . Environmental obesogens (bisphenols, phthalates and parabens) and their impacts on adipogenic transcription factors in the absence of dexamethasone in 3T3-L1 cells. J Steroid Biochem Mol Biol. 2021; 214:105994. DOI: 10.1016/j.jsbmb.2021.105994. View

20.

Sztalryd C, Brasaemle D . The perilipin family of lipid droplet proteins: Gatekeepers of intracellular lipolysis. Biochim Biophys Acta Mol Cell Biol Lipids. 2017; 1862(10 Pt B):1221-1232. PMC: 5595658. DOI: 10.1016/j.bbalip.2017.07.009. View