Mangum Lauren H, Howell George E, Chambers Janice E
Center for Environmental Health Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, MS, USA.
Center for Environmental Health Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, MS, USA.
Toxicol Lett. 2015 Oct 14;238(2):65-71. doi: 10.1016/j.toxlet.2015.07.009. Epub 2015 Jul 19.
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 (0.01-100μM) 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 (10μM) enhanced expression of fatty acid binding protein 4 and Sterol regulatory element-binding protein-1c at the 2.5 and 20μM concentrations. DDE (2.5, 10, and 20μM) 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.
全球肥胖症的发病率正以惊人的速度上升。最近，接触环境污染物，尤其是有机氯，如p,p'-二氯二苯二氯乙烯（DDE），被认为可能是肥胖症流行加剧的一个致病因素。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。使用次优分化混合剂，在DDE（0.01 - 100μM）存在的情况下诱导3T3 - L1前脂肪细胞分化。分化开始八天后，通过中性脂质染色、甘油三酯积累和终末分化标志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，接触DDE会导致细胞内中性脂质积累呈浓度依赖性增加。脂质积累的改变伴随着分化基因标志物的上调。在2.5和20μM浓度下，DDE（10μM）增强了脂肪酸结合蛋白4和固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20μM）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细胞中的脂肪生成和细胞内脂质积累。
