Environmental obesogens:: Organotins and endocrine disruption via nuclear receptor signaling
Environmental obesogens:: Organotins and endocrine disruption via nuclear receptor signaling
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DOI：
10.1210/en.2005-1129
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发表时间：
2006-06-01
期刊：
影响因子：
4.8
通讯作者：
Blumberg, Bruce
中科院分区：
文献类型：
--
作者：
Grun, Felix;Blumberg, Bruce
在过去的二十年中，肥胖和相关代谢综合征疾病的发病率急剧上升，成为全球健康危机。热量摄入增加和体力活动减少被认为是这一急剧上升的根本原因。然而，最近的研究结果强调了环境致肥胖剂的可能参与，异生物质化学物质可以破坏对脂肪形成和能量平衡的正常发育和稳态控制。环境雌激素，即具有雌激素潜力的化学品，已被报道使用体外模型系统干扰脂肪形成机制，但其他类别的内分泌干扰化学品现在也受到审查。有机锡是一类广泛存在的持久性有机污染物，对无脊椎动物和脊椎动物的内分泌都有很强的干扰作用。新的数据确定三丁基氯化锡和三苯基氯化锡作为类维生素A X受体（RXR α，RXR β和RXR γ）和过氧化物酶体增殖物激活受体γ的纳摩尔激动剂配体，这些核受体在脂质体内平衡和脂肪生成中起关键作用。环境致胖假说预测，有机锡不适当的受体激活将直接导致脂肪细胞分化和肥胖的易感性，和/或将使暴露个体在典型的高热量、高脂肪西方饮食的影响下对肥胖和相关代谢紊乱敏感。有机锡暴露与脂肪细胞分化和肥胖的联系为研究环境对人类健康和疾病的潜在影响开辟了一个重要的新领域。
Over the last two decades, the incidence of obesity and associated metabolic syndrome diseases has risen dramatically, becoming a global health crisis. Increased caloric intake and decreased physical activity are believed to represent the root causes of this dramatic rise. However, recent findings highlight the possible involvement of environmental obesogens, xenobiotic chemicals that can disrupt the normal developmental and homeostatic controls over adipogenesis and energy balance. Environmental estrogens, i.e. chemicals with estrogenic potential, have been reported to perturb adipogenic mechanisms using in vitro model systems, but other classes of endocrine-disrupting chemicals are now coming under scrutiny as well. Organotins represent one class of widespread persistent organic pollutants with potent endocrine-disrupting properties in both invertebrates and vertebrates. New data identify tributyltin chloride and triphenyltin chloride as nanomolar agonist ligands for retinoid X receptor (RXR alpha, RXR beta, and RXR gamma) and peroxisome proliferator-activated receptor gamma, nuclear receptors that play pivotal roles in lipid homeostasis and adipogenesis. The environmental obesogen hypothesis predicts that inappropriate receptor activation by organotins will lead directly to adipocyte differentiation and a predisposition to obesity and/or will sensitize exposed individuals to obesity and related metabolic disorders under the influence of the typical high-calorie, high-fat Western diet. The linking of organotin exposure to adipocyte differentiation and obesity opens an important new area of research into potential environmental influences on human health and disease.