Bisphenol A and its metabolites promote white adipogenesis and impair brown adipogenesis in vitro

Abstract

Bisphenol A (BPA), an obesogen, can disrupt adipogenesis in vitro, but these studies did not distinguish adipocytes as white or brown. BPA can be metabolized into BPA-glucuronide (BPA-G) and BPA-sulfate (BPA-S). These metabolites are not completely inactive in the body, but the related studies remain limited. In this study, preadipocytes isolated from mouse white and brown adipose tissues were treated with 0.1, 1, and 10 μM of BPA and its metabolites for 6 days, which are equivalent to the exposure level of general and occupational populations, to investigate and compare the effects of BPA and its metabolites on white and brown adipogenesis. The results showed that BPA and BPA-G increased lipid accumulation during white adipogenesis, whereas only BPA induced this same effect during brown adipogenesis. Moreover, BPA and its metabolites upregulated the expression of pan-adipogenic markers, such as peroxisome proliferator-activated receptor gamma (PPARγ), during white adipogenesis, whereas they downregulated that of PPARγ during brown adipogenesis. Additionally, BPA also inhibited the mRNA and protein expression of brown fat-specific markers (e.g., PPARγ coactivator 1–1alpha (PGC1-α) and uncoupling protein 1 (UCP1)), and mitochondrial activity during brown adipogenesis, and BPA-G also reduced the mRNA expression levels of Pgc1-α and Ucp1. These findings indicated that BPA induced different effects on white and brown adipogenesis, enhancing the former and hindering the latter. Despite less potent than BPA, BPA-G and BPA-S might also affect white and brown adipogenesis. This research provides in-depth insights into the obesogenic effects of BPA and the biological activities of its metabolites.