In Vitro Effects of Bisphenol A β-D-Glucuronide (BPA-G) on Adipogenesis in Human and Murine Preadipocytes.
In Vitro Effects of Bisphenol A β-D-Glucuronide (BPA-G) on Adipogenesis in Human and Murine Preadipocytes.
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DOI：
10.1289/ehp.1409143
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发表时间：
2015-12
影响因子：
10.4
通讯作者：
Atlas E
中科院分区：
文献类型：
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作者：
Boucher JG;Boudreau A;Ahmed S;Atlas E
接触双酚 A (BPA) 等常见环境物质与许多负面健康结果有关。在体内，BPA 迅速转化为其主要代谢物 BPA-葡萄糖醛酸 (BPA-G)，长期以来人们认为它不具有生物活性，因为它缺乏雌激素活性。然而，BPA-G 对细胞代谢的影响尚未得到表征。在本研究中，我们检查了 BPA-G 对脂肪生成的影响。通过量化脂质积累和脂肪形成标记物的表达，体外评估 BPA-G 对人和 3T3L1 鼠前脂肪细胞分化的影响。用 10 μM BPA-G 处理 3T3L1 前脂肪细胞可显着增加脂质积累、脂肪形成标志物甾醇调节元件结合因子 1 (SREBF1) 和脂蛋白脂肪酶 (LPL) 的 mRNA 表达，以及 LPL、aP2 和脂肪素的蛋白水平。用 BPA-G 处理原代人前脂肪细胞也诱导脂肪生成（根据 aP2 水平测定）。将细胞与雌激素受体 (ER) 拮抗剂氟维司群 (ICI) 共同处理可显着抑制 BPA-G 诱导的 LPL 和 aP2 水平升高，而单独使用 ICI 处理则没有效果。此外，BPA-G 没有表现出任何显着的雌激素活性。据我们所知，这项研究首次报道 BPA-G 诱导脂肪细胞分化，而不仅仅是一种无活性的代谢物。 BPA-G 诱导脂肪生成并被 ER 拮抗剂抑制，但没有表现出雌激素活性，这一事实表明它不具有经典的 ER 转录激活功能，并且通过仍有待确定的途径发挥作用。 Boucher JG、Boudreau A、Ahmed S、Atlas E. 2015。双酚 A β-D-葡萄糖苷酸 (BPA-G) 对人和小鼠前脂肪细胞脂肪生成的体外影响。环境健康视角 123：1287–1293； http://dx.doi.org/10.1289/ehp.1409143
Exposure 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. The 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. Treatment 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. To 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. Boucher 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