Prioritizing Environmental Chemicals for Obesity and Diabetes Outcomes Research: A Screening Approach Using ToxCast™ High-Throughput Data.
Prioritizing Environmental Chemicals for Obesity and Diabetes Outcomes Research: A Screening Approach Using ToxCast™ High-Throughput Data.
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DOI：
10.1289/ehp.1510456
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发表时间：
2016-08
影响因子：
10.4
通讯作者：
Thayer KA
中科院分区：
文献类型：
--
作者：
Auerbach S;Filer D;Reif D;Walker V;Holloway AC;Schlezinger J;Srinivasan S;Svoboda D;Judson R;Bucher JR;Thayer KA
糖尿病和肥胖症是美国和国外公众健康的主要威胁。了解我们环境中的化学品在这些条件的发展中所发挥的作用是环境健康领域的一个新问题，尽管确定和优先考虑文献中已经涉及的化学品进行测试是一项挑战。本综述旨在通过总结美国环境保护署（EPA）ToxCast™高通量筛选（HTS）计划的相关发现，帮助研究人员生成有关可能导致糖尿病和肥胖相关健康结果的化学物质的假设。我们的目标是利用高通量筛选数据，围绕对糖尿病或肥胖相关结果具有潜在兴趣的环境化学物质开发新的假设。我们鉴定了与糖尿病和肥胖相关的几种生物过程（外周组织中的胰岛素敏感性、胰岛和β细胞功能、脂肪细胞分化和进食行为）相关的ToxCast™测定靶标，并针对这些测定靶标提供了化学筛选数据，以鉴定潜在感兴趣的化学品。这种筛选级分析的结果表明，在与糖尿病和肥胖症相关的研究中考虑的环境化学品的范围比同行评审文献中发表的研究论文和评论所表明的要广泛得多。基于ToxCast™数据的假设测试也将有助于评估该HTS平台的预测效用。需要更多的研究，把这些筛选水平的分析背景下，但在这篇评论中提出的信息应促进新的假设的发展。奥尔巴赫S，Filer D，Reif D，步行者V，霍洛威AC，Schlezinger J，Srinivasan S，Svoboda D，Judson R，布赫JR，Thayer KA. 2016.为肥胖和糖尿病结果研究优先考虑环境化学品：使用ToxCast™高通量数据的筛选方法。环境健康展望124：1141-1154; http：dx.doi.org/10.1289/ehp.1510456
Diabetes and obesity are major threats to public health in the United States and abroad. Understanding the role that chemicals in our environment play in the development of these conditions is an emerging issue in environmental health, although identifying and prioritizing chemicals for testing beyond those already implicated in the literature is challenging. This review is intended to help researchers generate hypotheses about chemicals that may contribute to diabetes and to obesity-related health outcomes by summarizing relevant findings from the U.S. Environmental Protection Agency (EPA) ToxCast™ high-throughput screening (HTS) program. Our aim was to develop new hypotheses around environmental chemicals of potential interest for diabetes- or obesity-related outcomes using high-throughput screening data. We identified ToxCast™ assay targets relevant to several biological processes related to diabetes and obesity (insulin sensitivity in peripheral tissue, pancreatic islet and β cell function, adipocyte differentiation, and feeding behavior) and presented chemical screening data against those assay targets to identify chemicals of potential interest. The results of this screening-level analysis suggest that the spectrum of environmental chemicals to consider in research related to diabetes and obesity is much broader than indicated by research papers and reviews published in the peer-reviewed literature. Testing hypotheses based on ToxCast™ data will also help assess the predictive utility of this HTS platform. More research is required to put these screening-level analyses into context, but the information presented in this review should facilitate the development of new hypotheses. Auerbach S, Filer D, Reif D, Walker V, Holloway AC, Schlezinger J, Srinivasan S, Svoboda D, Judson R, Bucher JR, Thayer KA. 2016. Prioritizing environmental chemicals for obesity and diabetes outcomes research: a screening approach using ToxCast™ high-throughput data. Environ Health Perspect 124:1141–1154; http://dx.doi.org/10.1289/ehp.1510456