Unexpected Activity

Evidence for Obesogenicity of a BPA Metabolite Bisphenol A (BPA) has been implicated as an obesogen, a com-pound that alters lipid metabolism, promoting development of adipocytes (fat cells) and accumulation of fat.1,2 BPA is quickly converted in the body to its main metabolite, BPA β-D-glucuronide (BPA-G), which has been thought to be biologically inactive.3 But a study reported in this issue of EHP indicates that BPA-G, like its parent compound BPA, can induce precursor cells called preadipo-cytes to develop into mature fat cells.4 In one experiment the researchers treated mouse preadipocytes with 10 μM of BPA-G. This resulted in a significant increase in fat accumulation and stimulated protein expression of three adipogenic markers—lipoprotein lipase, aP2, and adipsin—in the mouse cells. In experiments with human preadipocytes, they found that both 0.05 and 0.25 μM BPA-G stimulated fat cell differentiation as determined by aP2 protein levels. However, co-exposure with fulves-trant—an estrogen-receptor (ER) antagonist used to treat some breast cancers—inhibited the changes that were seen with BPA-G alone.4 The authors also observed that BPA-G did not have direct estro-genic activity, unlike its parent compound BPA. At the same time, its effects on adipogenesis were inhibited by an ER antagonist. The authors suggest this could indicate an effect through nonclassical ER signaling—in other words, an effect that does not involve a direct interaction between the ER and DNA—but they acknowledge that other unidentified mechanisms also are possible.4 The authors included human cells in their experiments to assess whether there were differences in how different species respond. “As can be seen in the paper, the human cells were also responsive, ” says team leader Ella Atlas, a research scientist with Health Canada’s Environmental Health Science and Research Bureau. “We were surprised to find that BPA-G was active and that it seemed even more potent in the human preadipocytes.” BPA is used in a wide variety of products, including polycarbon-ate plastics, food and beverage containers, and coated papers (e.g.