Department of Environmental Health Science, College of Public Health, University of Georgia, 150 Green Street, Athens, GA 30602, USA..
Department of Environmental Health Science, College of Public Health, University of Georgia, 150 Green Street, Athens, GA 30602, USA.
Pestic Biochem Physiol. 2018 Sep;150:48-58. doi: 10.1016/j.pestbp.2018.07.003. Epub 2018 Jul 10.
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.
环境化学暴露可能是肥胖症流行率不断上升的一个因素。二嗪磷是一种有机磷杀虫剂，已广泛应用于农业，且有报道称一般人群会接触到二嗪磷。已知二嗪磷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联尚未得到充分研究。本研究旨在使用 3T3-L1 前脂肪细胞结合单细胞高内涵分析，来研究二嗪磷对脂肪生成的作用机制。结果表明，二嗪磷以剂量依赖性方式诱导脂滴积累。通过实时定量 RT-PCR 和 Western Blot 分别在不同剂量（0、1、10、100μM）的二嗪磷处理的 3T3-L1 细胞中，在脂肪生成的三个阶段（诱导、分化和成熟）检查脂肪生成调节蛋白和基因的动态变化。二嗪磷显著诱导转录因子 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）、脂联素和围脂滴蛋白的蛋白表达呈剂量和时间依赖性。同样，与相对对照相比，脂肪生成基因也呈剂量和时间依赖性显著诱导。本研究表明，二嗪磷在体外模型中促进脂质积累并激活脂肪生成信号通路。
