Bisphenol A diglycidyl ether induces adipogenic differentiation of multipotent stromal stem cells through a peroxisome proliferator-activated receptor gamma-independent mechanism.
Bisphenol A diglycidyl ether induces adipogenic differentiation of multipotent stromal stem cells through a peroxisome proliferator-activated receptor gamma-independent mechanism.
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DOI：
10.1289/ehp.1205063
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发表时间：
2012-07
影响因子：
10.4
通讯作者：
Blumberg B
中科院分区：
文献类型：
--
作者：
Chamorro-García R;Kirchner S;Li X;Janesick A;Casey SC;Chow C;Blumberg B
背景：双酚A(BPA)和双酚A二缩水甘油醚(BAGE)用于制造涂料和树脂，可从包装材料中浸出到食品中。大量研究表明，双酚A和BAGE可能会对人类健康产生不利影响，包括接触这类化学物质可能与传统的风险因素叠加，从而启动或加剧肥胖的发展。双酚A是一种可疑的肥胖原，而BAGE被描述为过氧化物酶体增殖物激活受体γ(PPARγ)拮抗剂，可以减少体重增加。目的：我们试图在生物学相关的细胞培养模型中测试BAGE的成脂作用。方法：用多能间充质干细胞(MSCs)研究BAGE和BPA的成脂能力，评价其对成脂、成骨、基因表达和核受体激活的影响。讨论：BAGE诱导人和小鼠MSCs以及小鼠3T3-L1前脂肪细胞成脂。相反，BPA不能促进MSCs的成脂，但能诱导3T3-L1细胞的成脂。BAGE暴露可诱导成脂基因表达谱，其诱导成脂和成脂基因表达的能力不被已知的PPARγ拮抗剂阻断。在瞬时转染实验中，BAGE和双酚A均不能激活或拮抗维甲酸X受体或PPARγ。结论：BAGE在低纳摩尔浓度下可以诱导MSCs和前脂肪细胞向成脂分化，与在有限的人类生物监测中观察到的结果相当。BAGE可能通过位于PPARγ下游或平行于PPAR BAGE的机制起作用。
Background: Bisphenol A (BPA) and bisphenol A diglycidyl ether (BADGE), used in manufacturing coatings and resins, leach from packaging materials into food. Numerous studies suggested that BPA and BADGE may have adverse effects on human health, including the possibility that exposure to such chemicals can be superimposed on traditional risk factors to initiate or exacerbate the development of obesity. BPA is a suspected obesogen, whereas BADGE, described as a peroxisome proliferator–activated receptor gamma (PPARγ) antagonist, could reduce weight gain. Objectives: We sought to test the adipogenic effects of BADGE in a biologically relevant cell culture model. Methods: We used multipotent mesenchymal stromal stem cells (MSCs) to study the adipogenic capacity of BADGE and BPA and evaluated their effects on adipogenesis, osteogenesis, gene expression, and nuclear receptor activation. Discussion: BADGE induced adipogenesis in human and mouse MSCs, as well as in mouse 3T3-L1 preadipocytes. In contrast, BPA failed to promote adipogenesis in MSCs, but induced adipogenesis in 3T3-L1 cells. BADGE exposure elicited an adipogenic gene expression profile, and its ability to induce adipogenesis and the expression of adipogenic genes was not blocked by known PPARγ antagonists. Neither BADGE nor BPA activated or antagonized retinoid “X” receptor (RXR) or PPARγ in transient transfection assays. Conclusions: BADGE can induce adipogenic differentiation in both MSCs and in preadipocytes at low nanomolar concentrations comparable to those that have been observed in limited human biomonitoring. BADGE probably acts through a mechanism that is downstream of, or parallel to, PPARγ.
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影响因子：
56.9
作者：
Hill, JO;Peters, JC
通讯作者：
Peters, JC
影响因子：
4.1
作者：
Fehlberg, S;Trautwein, S;Göke, R
通讯作者：
Göke, R
影响因子：
--
作者：
La Merrill, Michele;Birnbaum, Linda S.
通讯作者：
Birnbaum, Linda S.
影响因子：
--
作者：
Dhurandhar, NV
通讯作者：
Dhurandhar, NV
DOI：
10.1097/mco.0b013e3283034990
发表时间：
2008-07-01
影响因子：
3.1
作者：
Herbert, Alan
通讯作者：
Herbert, Alan