Casals-Casas C, Feige J N, Desvergne B
Center for Integrative Genomics, National Research Center Frontiers in Genetics, University of Lausanne, Switzerland.
Int J Obes (Lond). 2008 Dec;32 Suppl 6:S53-61. doi: 10.1038/ijo.2008.207.
The concept of endocrine disruption emerged over a decade ago with the observation that several natural or industrial compounds can interfere with estrogen and androgen signaling, and thereby affect both male and female reproductive functions. Since then, many endocrine-disrupting chemicals (EDCs) have been identified and the concept has been broadened to receptors regulating other aspects of endocrine pathways. In that context, interference of EDCs with receptors regulating metabolism has been proposed as a factor that could contribute to metabolic diseases such as obesity and diabetes. We review recent studies showing that several pollutants, including phthalates and organotins, interfere with PPAR (peroxisome proliferator-activated receptors) nuclear receptors and may thereby affect metabolic homeostasis. Particular emphasis is given on the mechanisms of action of these compounds. However, unlike what has been suspected, we provide evidence from mouse models suggesting that in utero exposure to the phthalate ester di-ethyl-hexyl-phthalate most likely does not predispose to obesity. Collectively, these studies define a subclass of EDCs that perturb metabolic signaling and that we propose to define as metabolic disruptors.
内分泌干扰的概念在十多年前出现，当时观察到几种天然或工业化合物能够干扰雌激素和雄激素信号传导，从而影响男性和女性的生殖功能。从那时起，许多内分泌干扰化学物质（EDCs）已被识别，并且这一概念已扩展到调节内分泌途径其他方面的受体。在这种背景下，有人提出EDCs对调节代谢的受体的干扰可能是导致肥胖和糖尿病等代谢性疾病的一个因素。我们回顾了最近的研究，这些研究表明包括邻苯二甲酸盐和有机锡在内的几种污染物会干扰过氧化物酶体增殖物激活受体（PPAR）核受体，从而可能影响代谢稳态。我们特别强调了这些化合物的作用机制。然而，与之前所怀疑的不同，我们从小鼠模型中提供的证据表明，子宫内暴露于邻苯二甲酸二（2-乙基己基）酯很可能不会导致肥胖。总的来说，这些研究定义了一类扰乱代谢信号的EDCs亚类，我们建议将其定义为代谢干扰物。
