Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling
- DOI
- Language of the publication
- English
- Date
- 2014-07-22
- Type
- Article
- Author(s)
- Boucher, Jonathan G.
- Husain, Mainul
- Rowan-Carroll, Andrea
- Williams, Andrew
- Yauk, Carole L.
- Atlas, Ella
- Publisher
- Wiley
Abstract
Objective: Exposure to the endocrine-disrupting chemical bisphenol A (BPA) is correlated with obesity and adipogenesis of human preadipocytes. However, the mechanism of action of BPA-induced human adipogenesis remains to be determined. Methods: Primary human preadipocytes were differentiated in the presence of 50 µM BPA or 1 µM dexamethasone (DEX) for 48 hours. Potential mechanisms of BPA-induced adipogenesis were evaluated using gene expression microarray analysis. Results: Microarray analysis revealed 373 differentially expressed genes following BPA treatment, including upregulation of sterol regulatory element binding factor 1 (SREBF1), a key regulator of lipid metabolism. For DEX-treated preadipocytes, 2167 genes were differentially expressed, including upregulation of the adipogenic marker lipoprotein lipase. Ingenuity Pathway Analysis was used to identify functional annotations of the gene expression changes associated with response to BPA and DEX. BPA exposure was associated with expression changes in the genes involved in triacylglycerol accumulation while DEX was linked to triacylglycerol and fatty acid metabolism. The analysis also revealed enrichment of genes following BPA exposure in the thyroid-receptor/retinoic X receptor (TR/RXR) and mammalian target of rapamycin (mTOR) signaling pathways. Conclusions: Our data suggest that potential mechanisms of action of BPA-induced adipogenesis involve SREBF1, the TR/RXR, and the mTOR pathways.
Plain language summary
Health Canada is responsible for the assessment and management of health risks to Canadians associated with exposure to products and chemicals in the environment. Bisphenol A (BPA) is a chemical used in the production of plastics found in a number of commercial products. BPA has certain biological activities analogous to hormones and in experimental animals it has been shown to cause weight gain and fat accumulation in specialised fat cells. To better understand the biological mechanisms underlying chemical impacts on metabolic processes that could affect fat development and accumulation, Health Canada investigated how BPA causes fat accumulation in human tissues by studying how genes respond in human fat cells exposed to this chemical in vitro. The results revealed that human fat cells exposed to BPA show changes to specific genes that are involved in how cells make and accumulate fat, as well as how fat cells regulate cholesterol levels within the cell. This study suggests that BPA does affect how human cells control fat and cholesterol levels at the cellular level and that it is biologically plausible that BPA could be contributing in some manner to weight gain and obesity. The results will help increase knowledge about the effects of BPA and will provide a better understanding of how chemicals may be impacting the development and accumulation of fat. This knowledge will be useful in developing test methods to screen for these effects.
Subject
- Health,
- Health and safety