Environmental chemical tributyltin augments adipocyte differentiation
Environmental chemical tributyltin augments adipocyte differentiation
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DOI：
10.1016/j.toxlet.2005.05.015
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发表时间：
2005-12-15
影响因子：
3.5
通讯作者：
Shimomura, A
中科院分区：
文献类型：
--
作者：
Inadera, H;Shimomura, A
影响肥胖和II型糖尿病的环境因素已经引起了科学界的关注。以前，有报道称急性有机锡中毒可诱导高甘油血症，但在胰岛组织中没有形态学异常，这表明这些化合物对脂肪组织有直接影响。因此，我们研究了三丁基锡（TBT）对脂肪细胞分化的影响。混合3T3-L1细胞与TBT孵育2天，无论是否添加异丁基甲基黄嘌呤、地塞米松和胰岛素（MDI），脂肪细胞中的脂质积累都大大增强。TBT诱导的这些形态学变化伴随着脂肪细胞分化标记物的表达，并呈剂量依赖性。与过氧化物酶体增殖激活受体(PPAR) γ拮抗剂GW9662共处理未抑制TBT的作用，提示观察到的TBT作用可能不依赖于PPAR γ。尽管有报道称TBT可发挥雄激素作用并抑制芳香酶活性，但用双氢睾酮或17 β -雌二醇治疗并不影响3T3-L1细胞中aP2的表达，这表明TBT的作用不是通过性类固醇发生的。这些发现表明，TBT可能是导致脂肪组织过度积累的环境化学物质之一，从而导致肥胖。2005爱思唯尔爱尔兰有限公司版权所有。
Scientific attention has been drawn to environmental factors that affect obesity and type II diabetes. Previously, acute organotin toxicosis was reported to induce hyperglycernia without morphological abnormalities in islet tissue, suggesting that these compounds have a direct effect on adipose tissue. Therefore, we investigated the effect of tributyltin (TBT) on adipocyte differentiation. When confluent 3T3-L1 cells were incubated with TBT for 2 days in the presence or absence of isobutyl methylxanthine, dexamethasone and insulin (MDI), the lipid accumulation in adipocytes was greatly enhanced. These morphological changes induced by TBT were accompanied by the expression of a differentiation marker for adipocytes in a dose-dependent manner. Co-treatment with the peroxisome proliferator-activated receptor (PPAR)gamma antagonist GW9662 did not inhibit the effect of TBT, suggesting that the observed effect of TBT may not be PPAR gamma-dependent. Although TBT was reported to exert androgenic effects and inhibit the activity of aromatase, treatments with dihydrotestosterone or 17 beta-estradiol did not influence the aP2 expression in 3T3-L1 cells, suggesting that the TBT effect does not occur via sex-steroids. These findings indicate that TBT may be one of the environmental chemicals that lead to excessive accumulation of adipose tissue, which can result in obesity. (c) 2005 Elsevier Ireland Ltd. All rights reserved.