Diazinon exposure activated transcriptional factors CCAAT-enhancer-binding proteins α (C/EBPα) and peroxisome proliferator-activated receptor γ (PPARγ) and induced adipogenesis in 3T3-L1 preadipocytes.
Diazinon exposure activated transcriptional factors CCAAT-enhancer-binding proteins α (C/EBPα) and peroxisome proliferator-activated receptor γ (PPARγ) and induced adipogenesis in 3T3-L1 preadipocytes.
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DOI：
10.1016/j.pestbp.2018.07.003
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发表时间：
2018-09
影响因子：
4.7
通讯作者：
Yin L
中科院分区：
文献类型：
--
作者：
Smith A;Yu X;Yin L
环境化学物质暴露可能是导致肥胖流行的一个因素。二嗪磷是一种有机磷杀虫剂，已广泛用于农业，并且有报道称普通人群接触过二嗪磷。已知二嗪农主要通过抑制乙酰胆碱酯酶 (AChE) 来诱导神经毒性作用。然而，其与脂肪生成失调的关系尚未得到充分研究。目前的研究旨在利用 3T3-L1 前脂肪细胞结合基于单细胞的高内涵分析来研究二嗪农对脂肪生成的影响机制。结果表明，二嗪农以剂量依赖性方式诱导脂滴积累。分别采用实时定量 RT-PCR 和 Western Blot 检测经不同剂量二嗪农（0、1、10、100 μM）处理的 3T3-L1 细胞在脂肪形成三个阶段（诱导、分化和成熟）脂肪形成调节蛋白和基因的动态变化。二嗪农显着诱导转录因子 CCAAT 增强子结合蛋白 α (C/EBPα) 和过氧化物酶体增殖物激活受体 γ (PPARγ) 及其下游蛋白、脂肪酸合成酶 (FASN)、乙酰辅酶 A 羧化酶 (ACC)、脂肪酸结合蛋白 4 (FABP4)、脂蛋白脂肪酶 (LPL)、脂联素和周脂质的蛋白表达，且呈剂量和时间依赖性。类似地，与相对对照相比，成脂基因以剂量和时间依赖性方式显着诱导。目前的研究表明，二嗪农在体外模型中促进脂质积累并激活脂肪形成信号通路。
Environmental chemical exposure could be a contributor to the increasing obesity epidemic. Diazinon, an organophosphate insecticide, has been widely used in the agriculture, and exposure of the general population to diazinon has been reported. Diazinon has been known to induce neurotoxic effects mainly through the inhibition of acetylcholinesterase (AChE). However, its association with dysregulation of adipogenesis has been poorly investigated. The current study aimed to examine the mechanism of diazinon’s effect on adipogenesis using the 3T3-L1 preadipocytes combined with a single-cell-based high-content analysis. The results showed that diazinon induced lipid droplet accumulation in a dose-dependent manner. The dynamic changes of adipogenic regulatory proteins and genes were examined at the three stages of adipogenesis (induction, differentiation, and maturation) in 3T3-L1 cells treated with various doses of diazinon (0, 1, 10, 100 μM) using real-time quantitative RT-PCR and Western Blot respectively. Diazinon significantly induced protein expression of transcriptional factors CCAAT-enhancer-binding proteins α (C/EBPα) and peroxisome proliferator-activated receptor γ (PPARγ), their downstream proteins, fatty acid synthase (FASN), acetyl CoA carboxylase (ACC), fatty acid-binding protein 4 (FABP4), lipoprotein lipase (LPL), adiponectin and perilipin in dose and time-dependent manners. Similarly, the adipogenic genes were significantly induced in a dose and time-dependent manner compared to the relative controls. The current study demonstrates that diazinon promotes lipid accumulation and activates the adipogenic signaling pathway in the in vitro model.
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影响因子：
2.9
作者：
Crumpton, TL;Seidler, FJ;Slotkin, TA
通讯作者：
Slotkin, TA
影响因子：
10.4
作者：
Coronado GD;Vigoren EM;Thompson B;Griffith WC;Faustman EM
通讯作者：
Faustman EM
DOI：
10.1097/ede.0000000000000489
发表时间：
2016-07
期刊：
Epidemiology (Cambridge, Mass.)
影响因子：
--
作者：
Deierlein AL;Wolff MS;Pajak A;Pinney SM;Windham GC;Galvez MP;Silva MJ;Calafat AM;Kushi LH;Biro FM;Teitelbaum SL;Breast Cancer and Environment Research Program
通讯作者：
Breast Cancer and Environment Research Program
影响因子：
82.9
作者：
Berg, AH;Combs, TP;Scherer, PE
通讯作者：
Scherer, PE
影响因子：
2.9
作者：
Adigun, Abayomi A.;Wrench, Nicola;Slotkin, Theodore A.
通讯作者：
Slotkin, Theodore A.