Is bisphenol A diglycidyl ether (BADGE) and obesogen?

描述（由申请人提供）：这是一项R21申请，旨在检验双酚A二缩水甘油醚（BADGE）在体内通过不依赖于PPAR 3的途径作为肥胖原的假设。产前和产后早期的事件，如母亲的营养，药物和化学品接触，接收，记住，然后在以后的生活中表现出健康后果。在美国，肥胖流行病每年花费超过1470亿美元，主要是通过增加医疗保健费用。新出现的证据支持环境因素在肥胖中的重要作用。其中之一是接触干扰内分泌的化学品。我们的初步结果表明，BADGE诱导脂肪形成在小鼠和人类多能间充质干细胞（MSC）通过一个途径，似乎不涉及一个关键的脂肪形成基因-过氧化物酶体增殖物激活受体γ（PPAR 3）。我们希望测试的假设，BADGE作为一种肥胖，在体内。提出了两个具体的目的来检验这一假设：1）BADGE暴露是否使小鼠易于增加脂肪形成和肥胖，如果是这样，它是否改变MSC隔室中的谱系分配？2)BADGE通过什么分子途径影响脂肪生成和肥胖？拟议的工作将促进快速进展，了解是否高容量的化学品，BADGE，作为一种肥胖，在体内，在环境相关剂量，并将提供洞察内分泌干扰化学品如何影响脂肪生成和肥胖。

DESCRIPTION (provided by applicant): This is an R21 application intended to test the hypothesis that bisphenol A diglycidyl ether (BADGE) acts as an obesogen, in vivo through a pathway that is independent of PPAR3. Prenatal and early postnatal events such as maternal nutrition, drug, and chemical exposure are received, remembered, and then manifested in health consequences later in life. The obesity epidemic costs more than $147 billion annually in the US, primarily by increasing health care costs. Emerging evidence supports an important role for environmental factors in obesity. Among these is exposure to endocrine disrupting chemicals. Our preliminary results demonstrate that BADGE induces adipogenesis in both mouse and human multipotent mesenchymal stem cells (MSCs) through a pathway that appears not to involve a key adipogenic gene - the peroxisome proliferator activated receptor gamma (PPAR3). We wish to test the hypothesis that BADGE acts as an obesogen, in vivo. Two specific aims are proposed to test this hypothesis: 1) Does BADGE exposure predispose mice to increased adipogenesis and obesity and if so, does it alter lineage allocation in the MSC compartment? 2) What molecular pathway does BADGE act through to influence adipogenesis and obesity? The proposed work will facilitate rapid progress in understanding whether the high volume chemical, BADGE, acts as an obesogen, in vivo, at environmentally relevant doses and will provide insights into how endocrine disrupting chemicals influence adipogenesis and obesity.