The obesogenic effects of Bisphenol A and its analogues are differentially regulated via PPARγ transactivation in mouse 3T3-L1 cells

IF 2.6 3区医学 Q3 TOXICOLOGY Toxicology in Vitro Pub Date : 2025-01-20 DOI:10.1016/j.tiv.2025.106009

Jennifer Crosthwait , Syed Syeddan , Ella Atlas

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Abstract

Exposure to environmental pollutants with obesogenic activity is being recognised as one of the contributing factors to the obesity epidemic. Bisphenol A (BPA) has been shown to stimulate adipogenesis in both human and mouse preadipocytes, to increase body weight and affect lipid metabolism in animal and epidemiological studies. Regulatory action and public concern has prompted industry to replace BPA with other structurally similar analogues that may have similar effects.

In this study we investigated the effects of fifteen BPA analogues on adipogenesis in the mouse 3 T3-L1 pre-adipocyte cell model in order to determine their adipogenic activity relative to BPA. 3 T3-L1 cells were treated with increasing concentrations of BPA and replacements and mRNA expression of the mature adipocyte markers fatty acid binding protein 4 (Fabp4), perilipin (Plin) lipoprotein lipase (Lpl)and peroxisome proliferator-activated receptor (Ppar)γ and lipid accumulation were assessed. In addition, a luciferase reporter assay for PPARγ transactivation was employed to investigate mechanism of action.

Our results show that BPC, BPS-MAE, BPS-MPE and TGSA, were the most adipogenic bisphenols, as shown by a robust increase in lipid accumulation and mRNA expression of adipogenic markers. BPS-MPE, BPC, BTUM, TGSA and D8 increased PPARγ transcriptional activity. Despite its ability to activate PPARγ in the transcriptional assay D8 did not affect adipogenesis in this cell model.

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来源期刊

Toxicology in Vitro 医学-毒理学

CiteScore

6.50

自引率

3.10%

发文量

181

审稿时长

65 days

期刊介绍： Toxicology in Vitro publishes original research papers and reviews on the application and use of in vitro systems for assessing or predicting the toxic effects of chemicals and elucidating their mechanisms of action. These in vitro techniques include utilizing cell or tissue cultures, isolated cells, tissue slices, subcellular fractions, transgenic cell cultures, and cells from transgenic organisms, as well as in silico modelling. The Journal will focus on investigations that involve the development and validation of new in vitro methods, e.g. for prediction of toxic effects based on traditional and in silico modelling; on the use of methods in high-throughput toxicology and pharmacology; elucidation of mechanisms of toxic action; the application of genomics, transcriptomics and proteomics in toxicology, as well as on comparative studies that characterise the relationship between in vitro and in vivo findings. The Journal strongly encourages the submission of manuscripts that focus on the development of in vitro methods, their practical applications and regulatory use (e.g. in the areas of food components cosmetics, pharmaceuticals, pesticides, and industrial chemicals). Toxicology in Vitro discourages papers that record reporting on toxicological effects from materials, such as plant extracts or herbal medicines, that have not been chemically characterized.