Interference of pollutants with PPARs: endocrine disruption meets metabolism
Interference of pollutants with PPARs: endocrine disruption meets metabolism
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DOI：
10.1038/ijo.2008.207
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发表时间：
2008-12-01
影响因子：
4.9
通讯作者：
Desvergne, B.
中科院分区：
文献类型：
--
作者：
Casals-Casas, C.;Feige, J. N.;Desvergne, B.
内分泌干扰的概念出现在十多年前，观察到几种天然或工业化合物可以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品（EDCs）已被确定和概念已扩大到受体调节内分泌途径的其他方面。在这种情况下，内分泌干扰物与受体调节代谢已被提出作为一个因素，可能有助于代谢疾病，如肥胖症和糖尿病。我们回顾最近的研究表明，几种污染物，包括邻苯二甲酸酯和有机锡，干扰过氧化物酶体增殖物激活受体（过氧化物酶体增殖物激活受体）核受体，从而可能影响代谢稳态。特别强调的是这些化合物的作用机制。然而，与怀疑的不同，我们提供的小鼠模型证据表明，在子宫内暴露于邻苯二甲酸二乙酯己基邻苯二甲酸酯最有可能不会导致肥胖。总的来说，这些研究定义了一个干扰代谢信号的内分泌干扰物亚类，我们建议将其定义为代谢干扰物。
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.