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重复 Nature Communications:干细胞平台发现食品添加剂破坏人体激素并导致肥胖

2017-08-14 文姜 生物探索

添加到早餐麦片和其他日常产品中的化学物质会使你肥胖吗?动物实验中越来越多的证据表明答案可能“是”,但在人类中证实这些发现至今仍面临着难以逾越的障碍。8月9日发表在Nature Communications上美国Cedars-Sinai医疗中心的研究人员开发了一种新的平台和操作方法来测试内分泌干扰物对人类的影响。


添加到早餐麦片和其他日常产品中的化学物质会使你肥胖吗?动物实验中越来越多的证据表明答案可能“是”,但在人类中证实这些发现至今仍面临着难以逾越的障碍。8月9日发表在Nature Communications上美国Cedars-Sinai医疗中心的研究人员开发了一种新的平台和操作方法来测试内分泌干扰物对人类的影响。

1添加剂破坏联系肠道和大脑之间的荷尔蒙

这项研究测试的三种化学物质在现代生活中使用频繁。

Butylhydroxytoluene(BHT)是一种抗氧化剂,通常添加到早餐谷类食品和其它食品中保护营养成分和防止脂肪酸败;全氟辛酸(perfluorooctanoic acid,PFOA)是一种具有热稳定性、疏油、疏水的高分子表面活性剂,用在炊具,纺织品和清洗剂等上;三丁基锡(tributyltin,TBT)是船舶防水涂料,这种用途会使其进入水中积聚在海鲜里。

研究人员利用人类干细胞生成的荷尔蒙产生组织来证明,长期接触这些化学物质会干扰从消化系统传给大脑的信号,这些信号会让人们知道吃饭时“饱”了。当这个信号系统发生故障时,人们可能会继续进食,导致体重增加。

通讯作者Dhruv Sareen博士说:“我们发现,这些化学物质破坏联系肠道和大脑之间的荷尔蒙。当我们三种一起测试时,联合的力量更为强劲。”Sareen说BHT产生的不利影响最强。

而其他科学家已经证明这些化合物可以破坏实验室动物的激素系统。Sareen说新的研究是第一个使用人类干细胞和组织来证明化合物可能扰乱人的肠-脑信号和预防肥胖的关键激素。

该研究所所长Clive Svendsen博士说:“这是一个里程碑式的研究,大大提高了我们对内分泌干扰物的了解——可能会损害人体的内分泌系统,导致美国肥胖的流行。”根据联邦统计数据,超过三分之一的美国成年人被认为是肥胖的。

2诱导多能干细胞分化的组织有效检测化学物质对人体作用

研究人员认为为这项研究开发的新的测试系统有可能提供一种急需的、安全的和成本效益高的方法,用来评估成千上万现有和新的化学物质对环境健康的影响。

在他们的实验中,Sareen和他的团队首先从成人中获得血液样本,然后通过重编程基因,将细胞转化为诱导多能干细胞。然后,利用这些干细胞,研究人员培育出人类的上皮组织,这些组织是在肠道内以及大脑下丘脑区域的神经元组织,它们调节食欲和新陈代谢。

研究人员然后将组织一个接一个地、之后结合地暴露于BHT,PFOA和TBT,观察细胞内发生了什么。他们发现这些化学物质破坏了那些保持信号激素结构并从细胞中运输出来的网络,从而使它们失效。这些化学物质也破坏了线粒体。

因为化学损伤发生在早期阶段的“年轻”的细胞,研究结果提示了一个有缺陷的激素系统可能会影响怀孕的母亲和她在子宫的胎儿。而其他的科学家已经发现,在动物实验中,内分泌干扰物的影响可以传给子孙后代,这个过程还没有被证明在人类身上发生。



3该研究让化学品人体健康风险评估更容易更便宜

根据美国卫生和福利部门的国家毒理学计划,每天有8万多种化学品在美国注册,用于日常用品,如食品、个人护理用品、家用清洁剂和草坪护理产品。虽然该计划在其网站上表明,只有相对较少的化学物质被认为对人类健康构成重大威胁,但它也指出:“我们不知道这些化学物质对我们的健康有多大影响。”

成本和伦理问题,包括对可能有害的物质进行暴露后人体受试者的健康风险,是检验许多化学品安全性的障碍之一。因此,许多广泛使用的化合物仍然未在人类评估其健康影响,特别是对激素系统。

Sareen说:“通过在实验室实际人体组织中检测这些化学物质,我们可以使这些潜在的评价更容易进行,更具成本效益。”

参考资料:

Uthra Rajamani , Andrew R. Gross , Camille Ocampo ,et,al.Endocrine disruptors induce perturbations in endoplasmic reticulum and mitochondria of human pluripotent stem cell derivatives.Nat Commun. 2017 Aug 9;8(1):219. doi: 10.1038/s41467-017-00254-8.

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