Mo-Im Kim Nursing Research Institute, College of Nursing, Yonsei University, 03722 Seoul, Republic of Korea.
Biobehavioral Research Center, College of Nursing Yonsei University, 03722 Seoul, Republic of Korea.
Life Sci. 2022 Jan 1;288:120151. doi: 10.1016/j.lfs.2021.120151. Epub 2021 Nov 18.
Obesogens are a type of endocrine-disrupting chemicals (EDCs) that disrupt the human endocrine system, resulting in obesity and metabolic disease. Several obesogens, including bisphenol A, tolylfluanid, and some pesticides, have been identified and studied previously; however, the underlying molecular mechanisms by which obesogens interfere with adipogenesis and induce insulin resistance in adipocyte remain unknown. This study aims to determine which type of chemical is the most potent obesogen and to investigate its effect on adipogenesis-related gene expressions. 3T3-L1, a pre adipocyte cell line, was differentiated into mature adipocytes with either vehicle or various obesogens, including bisphenol A, tolylfluanid, and endrin, as well as corticosterone, at the same dose. Subsequently, intracellular and secreted triglyceride levels were measured, and the expression of genes and proteins involved in adipogenesis and lipogenesis was investigated. We found that endrin was the most potent regulator of adipogenic differentiation, as compared to tolylfluanid, bisphenol A, and corticosterone. Endrin increased intracellular and secreted triglyceride levels and enhanced the expression of adipogenic transcription factors as well as the terminal differentiation marker in a dose-dependent manner. During the early stages of differentiation, endrin enhanced mammalian target of rapamycin (mTOR) activity, which was suppressed by the pharmacological blockade of the protein kinase B-mTOR pathway, with repressed adipogenic differentiation. However, endrin did not change the expression levels of the downstream members of the mTOR signaling pathway or proteins related to lipolysis in response to insulin. Thus, we suggest that endrin potentiates early-stage adipogenic differentiation by activating the mTOR pathway.
肥胖物是一种内分泌干扰化学物质 (EDCs)，它们会干扰人体内分泌系统，导致肥胖和代谢疾病。先前已经鉴定和研究了几种肥胖物，包括双酚 A、甲苯氟脲和一些杀虫剂；然而，肥胖物干扰脂肪生成并在脂肪细胞中诱导胰岛素抵抗的潜在分子机制尚不清楚。本研究旨在确定哪种化学物质是最有效的肥胖物，并研究其对脂肪生成相关基因表达的影响。3T3-L1 是一种前脂肪细胞系，用载剂或各种肥胖物（包括双酚 A、甲苯氟脲和艾氏剂）以及皮质酮在相同剂量下分化为成熟脂肪细胞。随后，测量细胞内和分泌的甘油三酯水平，并研究与脂肪生成和脂肪生成相关的基因和蛋白质的表达。我们发现，与甲苯氟脲、双酚 A 和皮质酮相比，艾氏剂是脂肪生成分化的最有效调节剂。艾氏剂以剂量依赖性方式增加细胞内和分泌的甘油三酯水平，并增强脂肪生成转录因子的表达以及终末分化标记。在分化的早期阶段，艾氏剂增强了哺乳动物雷帕霉素靶蛋白 (mTOR) 的活性，而蛋白激酶 B-mTOR 通路的药理学阻断抑制了脂肪生成分化。然而，艾氏剂并没有改变 mTOR 信号通路的下游成员或对胰岛素反应的脂肪分解相关蛋白的表达水平。因此，我们认为艾氏剂通过激活 mTOR 通路增强早期脂肪生成分化。
