Is bisphenol A diglycidyl ether (BADGE) and obesogen?

描述（由申请人提供）：这是一份R21申请，旨在测试双酚A二甘油酯醚（BADGE）在体内通过独立于PPAR3的途径作为致肥物质的假设。产前和产后早期的事件，如产妇营养、药物和化学品暴露，被接受、记住，然后在以后的生活中表现为健康后果。在美国，肥胖流行病每年花费超过1470亿美元，主要是增加了医疗保健费用。新出现的证据支持环境因素在肥胖中扮演重要角色。其中之一就是接触内分泌干扰物。我们的初步结果表明，BADGE诱导小鼠和人多能间充质干细胞（MSCs）的脂肪形成，其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 (PPAR3)。我们希望在体内验证BADGE作为肥胖原的假设。为了验证这一假设，提出了两个具体的目标：1)暴露于BADGE是否使小鼠容易增加脂肪生成和肥胖，如果是这样，它是否会改变MSC隔间中的谱系分配？2) BADGE通过哪些分子途径影响脂肪形成和肥胖？拟议的工作将促进在了解高容量化学物质BADGE是否在体内以环境相关剂量作为致肥因子方面取得快速进展，并将为内分泌干扰化学物质如何影响脂肪形成和肥胖提供见解。

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. PUBLIC HEALTH RELEVANCE: Obesity is a major public health problem. We propose to elucidate how maternal and early life programming of adipose tissue development is influenced by the endocrine disrupting chemical, bisphenol A diglycidyl ether (BADGE). The successful completion of this research will make important contributions to understanding the developmental programming of obesity, how obesogens affect this process, and what is the contribution of altered stem cell programming.