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News | Science Selections December 2015 | Volume 123 | Issue 12

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Environ Health Perspect; DOI:10.1289/ehp.123-A303

Unexpected Activity: Evidence for Obesogenicity of a BPA Metabolite

Wendee Nicole has written for Discover, Scientific American, and other publications.

About This Article open

Citation: Nicole W. 2015. Unexpected activity: evidence for obesogenicity of a BPA metabolite. Environ Health Perspect 123:A303; http://dx.doi.org/10.1289/ehp.123-A303

Published: 1 December 2015

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Related EHP Article

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

Jonathan G. Boucher, Adèle Boudreau, Shaimaa Ahmed, and Ella Atlas

Bisphenol A (BPA) has been implicated as an obesogen, a compound 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 preadipocytes 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 fulvestrant—an estrogen-receptor (ER) antagonist used to treat some breast cancers—inhibited the changes that were seen with BPA-G alone.4

Differentiating adipocytePreadipocytes are a renewable source of new adipocytes (fat cells), which accumulate and store lipids for use as energy. Obesogens spur more preadipocytes to differentiate into fat cells and cause mature fat cells to accumulate more lipids.

© Gary Carlson/Science Source

The authors also observed that BPA-G did not have direct estrogenic 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 polycarbonate plastics, food and beverage containers, and coated papers (e.g., thermal receipts).5 The U.S. Food and Drug Administration (FDA) currently considers BPA safe at the levels occurring in food and food packaging.6 FDA researchers have reviewed the new study, says spokeswoman Marianna Naum, and have determined that the results do not provide a basis for altering the FDA’s assessment at this point. “This assessment remains consistent with Health Canada’s own assessment of BPA safety7 as well as that of the European Food Safety Authority8,” Naum says.

But the findings raise important questions that must be addressed, given the ubiquity of exposure to BPA.5 “This is an interesting paper that demonstrates a possible in vivo function for BPA-glucuronide which has heretofore been viewed as an inactive metabolite,” says Bruce Blumberg, a biology professor at the University of California, Irvine, who was not involved with the study. “If these authors are correct, then the argument that BPA is immediately rendered inactive by conjugation to BPA-glucuronide after ingestion, making it harmless, is inaccurate and misleading.”


References

1. Masuno H, et al. Bisphenol A accelerates terminal differentiation of 3T3-L1 cells into adipocytes through the phosphatidylinositol 3-kinase pathway. Toxicol Sci 84(2):319–327 (2005); PMID: [Pubmed].

2. Wang J, et al. The environmental obesogen bisphenol A promotes adipogenesis by increasing the amount of 11β-hydroxysteroid dehydrogenase type 1 in the adipose tissue of children. Int J Obes (Lond) 37(7):999–1005 (2013); doi: 10.1038/ijo.2012.173.

3. Volkel W, et al. Metabolism and kinetics of bisphenol A in humans at low doses following oral administration. Chem Res Toxicol 15(10):1281–1287 (2002); PMID: [Pubmed].

4. Boucher JG, et al. In vitro effects of bisphenol A β-D-glucuronide (BPA-G) on adipogenesis in human and murine preadipocytes. Environ Health Perspect 123(12):1287–1293 (2015); doi: 10.1289/ehp.1409143.

5. Vandenberg LN, et al. Urinary, circulating, and tissue biomonitoring studies indicate widespread exposure to bisphenol A. Environ Health Perspect 118(8):1055–1070 (2010); doi: 10.1289/ehp.0901716.

6. FDA. Bisphenol A (BPA): Use in Food Contact Application [website]. Silver Spring, MD:U.S. Food and Drug Administration (updated 6 January 2015). Available: http://www.fda.gov/NewsEvents/PublicHeal​thFocus/ucm064437.htm [accessed 5 November 2015].

7. Health Canada. Bisphenol A [website]. Ottawa, Ontario:Health Canada (updated 15 December 2014). Available: http://www.hc-sc.gc.ca/fn-an/securit/pac​kag-emball/bpa/index-eng.php [accessed 5 November 2015].

8. EFSA. Bisphenol A [website]. Parma, Italy:European Food Safety Authority (updated 28 October 2014). Available: http://www.efsa.europa.eu/en/topics/topi​c/bisphenol [accessed 5 November 2015].



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