In Vitro Effects of Bisphenol A β -D-Glucuronide (BPA-G) on Adipogenesis in Human and Murine Preadipocytes

Abstract

BackgroundExposure to common environmental substances, such as bisphenol A (BPA), has been associated with a number of negative health outcomes. In vivo, BPA is rapidly converted to its predominant metabolite, BPA-glucuronide (BPA-G), which has long been believed to be biologically inactive because it lacks estrogenic activity. However, the effects of BPA-G on cellular metabolism have not been characterized. In the present study we examined the effect of BPA-G on adipogenesis.MethodsThe effect of BPA-G on the differentiation of human and 3T3L1 murine preadipocytes was evaluated in vitro by quantifying lipid accumulation and the expression of adipogenic markers.ResultsTreatment of 3T3L1 preadipocytes with 10 μM BPA-G induced a significant increase in lipid accumulation, mRNA expression of the adipogenic markers sterol regulatory element binding factor 1 (SREBF1) and lipoprotein lipase (LPL), and protein levels of LPL, aP2, and adipsin. Treatment of primary human preadipocytes with BPA-G also induced adipogenesis as determined by aP2 levels. Co-treatment of cells with the estrogen receptor (ER) antagonist fulvestrant (ICI) significantly inhibited the BPA-G–induced increase in LPL and aP2 levels, whereas treatment with ICI alone had no effect. Moreover, BPA-G did not display any significant estrogenic activity.ConclusionsTo our knowledge, this study is the first to report that BPA-G induces adipocyte differentiation and is not simply an inactive metabolite. The fact that BPA-G induced adipogenesis and was inhibited by an ER antagonist yet showed no estrogenic activity suggests that it has no classical ER transcriptional activation function and acts through a pathway that remains to be determined.CitationBoucher JG, Boudreau A, Ahmed S, Atlas E. 2015. In vitro effects of bisphenol A β-D-glucuronide (BPA-G) on adipogenesis in human and murine preadipocytes. Environ Health Perspect 123:1287–1293; http://dx.doi.org/10.1289/ehp.1409143

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“…Further investigation revealed statistically significant increases in mRNA expression of adipogenic markers SREBF1 and LPL after 6-days post-treatment with 10μM BPA-G (Boucher et al 2015). BPA-G showed no estrogen receptor transcriptional activity indicating action occurs through an unknown pathway (Boucher et al 2015). Thus, glucuorination of BPA, for example, may only change the resulting biological disruption rather than the general disruptive capabilities of the compound itself.…”

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“…Furthermore, Boucher et al (2015) showed treatment of human and 3T3L1 murine preadipocytes with 0.01-10μM BPA-glucuronide (BPA-G) for 8-days exhibited significant lipid accumulation and induction of adipocyte differentiation at the 10μM exposure level using Nile Red staining and quantification. Further investigation revealed statistically significant increases in mRNA expression of adipogenic markers SREBF1 and LPL after 6-days post-treatment with 10μM BPA-G (Boucher et al 2015). BPA-G showed no estrogen receptor transcriptional activity indicating action occurs through an unknown pathway (Boucher et al 2015).…”