Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on adipogenic differentiation and insulin-induced glucose uptake in 3T3-L1 cells
Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on adipogenic differentiation and insulin-induced glucose uptake in 3T3-L1 cells
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DOI：
10.1016/j.jhazmat.2010.06.081
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发表时间：
2010-10-15
影响因子：
13.6
通讯作者：
Yeh, Szu-Ching
中科院分区：
文献类型：
--
作者：
Hsu, Hsin-Fen;Tsou, Tsui-Chun;Yeh, Szu-Ching
二恶英暴露与人类II型糖尿病呈正相关。由于亲脂性二恶英主要在脂肪组织中积累，本研究旨在确定二恶英是否会导致脂肪细胞代谢功能障碍。我们使用3 T3-L1细胞作为体外模型，分析了2，3，7，8-四氯二苯并-p-二恶英（TCDD）（一种二恶英模型）对脂肪形成分化、葡萄糖摄取和脂解的影响。通过油滴形成和脂肪形成标记基因表达，包括过氧化物酶体增殖物激活受体γ（过氧化物酶体增殖物激活受体γ）、C/EBP α（CCAAT/增强子结合蛋白α）和Glut 4（葡萄糖转运蛋白4型），确定TCDD抑制脂肪形成分化。使用完全分化的313-L1脂肪细胞评估TCDD对葡萄糖摄取的影响，揭示TCDD显著减弱胰岛素诱导的葡萄糖摄取，并呈剂量依赖性。芳香烃受体（AhR）抑制剂α-萘甲酮（α-NF）的抑制，并没有阻止TCDD对葡萄糖摄取的抑制作用，表明TCDD减弱胰岛素诱导的葡萄糖摄取在AhR-独立的方式。甘油释放法测定TCDD对脂肪分解的影响。我们发现，TCDD对异丙肾上腺素诱导的完全分化的313-L1脂肪细胞甘油释放没有显着影响。这些结果提供了TCDD对脂肪细胞代谢的影响的体外证据，表明二恶英暴露在胰岛素抵抗和II型糖尿病的发展。(C)2010 Elsevier B. V.保留所有权利。
Dioxin exposure has been positively associated with human type II diabetes. Because lipophilic dioxins accumulate mainly in adipose tissue, this study aimed to determine if dioxins induce metabolic dysfunction in fat cells. Using 3T3-L1 cells as an in vitro model, we analyzed the effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a model dioxin, on adipogenic differentiation, glucose uptake, and lipolysis. TCDD inhibited adipogenic differentiation, as determined by using oil droplet formation and adipogenic marker gene expression, including PPAR gamma (peroxisome proliferator-activated receptor gamma), C/EBP alpha (CCAAT/enhancer-binding protein alpha), and Glut4 (glucose transporter type 4). Effects of TCDD on glucose uptake were evaluated using fully differentiated 313-L1 adipocytes, revealing that TCDD significantly attenuated insulin-induced glucose uptake dose dependently. Inhibition of aryl hydrocarbon receptor (AhR) by alpha-naphthoflavone (alpha-NF), an AhR inhibitor, did not prevent the inhibitory effect of TCDD on glucose uptake, suggesting that TCDD attenuates insulin-induced glucose uptake in an AhR-independent manner. Effects of TCDD on lipolysis were determined using glycerol release assay. We found that TCDD had no marked effect on isoproterenol-induced glycerol release in fully differentiated 313-L1 adipocytes. These results provide in vitro evidence of TCDD's effects on fat cell metabolism, suggesting dioxin exposure in development of insulin resistance and type II diabetes. (C) 2010 Elsevier B.V. All rights reserved.