Bisphenol A Accelerates Terminal Differentiation of 3T3-L1 Cells into Adipocytes through the Phosphatidylinositol 3-Kinase Pathway

Abstract

In order to identify whether bisphenol A (BPA) acts as an adipogenic agent, following the hormonal induction of differentiation into adipocytes, 3T3-L1 cells were treated for six days with BPA alone. Treatment with BPA increased the triacylglycerol (TG) content of the cultures, increased the percentage of Oil Red O-staining cells in the cultures, and increased the levels of lipoprotein lipase (LPL) and adipocyte-specific fatty acid binding protein (aP2) mRNAs. These findings indicate that BPA was able to accelerate terminal differentiation of 3T3-L1 cells into adipocytes. LY294002, a chemical inhibitor of phosphatidylinositol 3-kinase (PI 3-kinase), blocked completely the increasing effect of BPA on TG accumulation and expression of LPL and aP2 mRNAs. Western blot analysis revealed that BPA increased the level of phosphorylated Akt kinase. Based on these findings, we concluded that BPA acted through the PI 3-kinase and Akt kinase pathway, resulting in increased TG accumulation and expression of adipocyte genes. The structure-activity relationship for BPA-related chemicals was examined. Eight derivatives of BPA (three diphenylalkanes with different substituents at the central carbon atom, three diphenylalkanes with ester bonds on hydroxyl groups in the phenolic rings, one bisphenol consisting of a sulphur atom at the central position, one chemical with cyanic groups, instead of hydroxyl groups, in the phenolic rings) accelerated terminal adipocyte differentiation and their potencies to increase TG accumulation were 73-97% of that of BPA. Two diphenylalkanes with ether bonds on hydroxyl groups and two alkylphenols (4-nonylphenol and 4-tert-octylphenol) did not have the ability to accelerate terminal adipocyte differentiation.

Expression of Concern: Laccase treatment impairs bisphenol A‐induced cancer cell proliferation affecting estrogen receptor α‐dependent rapid signals

“…Rapid modulation of ERK and AKT signaling in response to BPA has been observed in neurons, immune cells, and during brain development (14,(40)(41)(42). As far as we know, no information is available on the involvement of these BPA-induced rapid responses on cancer cell proliferation.…”

Urinary bisphenol A and obesity in adults: results from the Canadian Health Measures Survey

“…For example, BPA has been shown to promote adipocyte differentiation and fat accumulation, 9 as well as bind to estrogen receptors on adipocytes and inhibit the release of the hormone adiponectin. 37 While most animal studies focused on in utero exposure, Miyawaki et al 10 showed that BPA exposure during both perinatal and postnatal periods led to weight gain in mice.…”

Perinatal and Postnatal Exposure to Bisphenol A Increases Adipose Tissue Mass and Serum Cholesterol Level in Mice

“…Obesity is the result of an increase in body adipose tissue mass produced by either an enlargement of adipocytes or an increased number of adipocytes or both. We previously found that BPA not only had the ability to trigger 3T3-L1 fibroblasts to differentiate into adipocytes 11) , but also the ability to accelerate terminal adipocyte differentiation 12) …”