Exposure to p,p'-DDE enhances differentiation of 3T3-L1 preadipocytes in a model of sub-optimal differentiation.

Exposure to p,p'-DDE enhances differentiation of 3T3-L1 preadipocytes in a model of sub-optimal differentiation.
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DOI:
10.1016/j.toxlet.2015.07.009
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发表时间:
2015-10-14
期刊:
影响因子:
3.5
通讯作者:
Chambers JE
Chambers JE
中科院分区:
医学3区
文献类型:
--
作者:
Mangum LH;Howell GE 3rd;Chambers JE

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全世界肥胖症的发病率正以惊人的速度增加。最近,接触环境污染物,特别是有机氯,如对,对'-二氯二苯基二氯乙烯(DDE),被认为是导致肥胖流行的可能致病因素。本研究的目的是评估 DDE 在次优分化模型中改变脂肪生成的能力。在 DDE (0.01–100 μM) 存在下,使用次优分化混合物诱导 3T3-L1 前脂肪细胞分化。分化开始后八天,通过中性脂质染色、甘油三酯积累和终末分化标记物的表达来评估脂肪生成。通过油红 O 染色和甘油三酯测定确定,暴露于 DDE 会导致细胞内中性脂质积累浓度依赖性增加。脂质积累的变化伴随着分化遗传标记的上调。 DDE (10 μM) 在 2.5 和 20 μM 浓度下增强脂肪酸结合蛋白 4 和甾醇调节元件结合蛋白-1c 的表达。与次优载体对照(0.05% 乙醇)相比,DDE(2.5、10 和 20 μM)诱导瘦素和脂肪酸合酶上调。我们的结果表明,DDE 能够通过上调负责脂质储存的分子靶点来增强 3T3-L1 细胞的脂肪生成和细胞内脂质积累。
The incidence of obesity is increasing worldwide at an alarming rate. Recently, exposure to environmental contaminants, especially organochlorines such as p,p′-dichlorodiphenyldichloroethylene (DDE), has been implicated as a possible causative factor in the increasing obesity epidemic. The objective of this study was to evaluate the ability of DDE to alter adipogenesis in a model of sub-optimal differentiation. 3T3-L1 preadipocytes were induced to differentiate in the presence of DDE (0.01–100 μM) using a sub-optimal differentiation cocktail. Eight days after the initiation of differentiation, adipogenesis was assessed through neutral lipid staining, triglyceride accumulation, and expression of markers of terminal differentiation. Exposure to DDE induced a concentration dependent increase in intracellular neutral lipid accumulation as determined by Oil Red O staining and triglyceride assay. Alterations in lipid accumulation were accompanied by upregulation of genetic markers of differentiation. DDE (10 μM) enhanced expression of fatty acid binding protein 4 and Sterol regulatory element-binding protein-1c at the 2.5 and 20 μM concentrations. DDE (2.5, 10, and 20 μM) induced upregulation of leptin and fatty acid synthase, as compared to sub-optimal vehicle control (0.05% ethanol). Our results indicate that DDE is capable of enhancing adipogenesis and intracellular lipid accumulation in 3T3-L1 cells through upregulation of molecular targets responsible for lipid storage.
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