Reproductive and Genetic Center, National Research Institute for Family Planning, No. 12, Dahuisi Rd., Beijing 100081, PR China.
Toxicol Appl Pharmacol. 2012 Aug 15;263(1):102-10. doi: 10.1016/j.taap.2012.06.003. Epub 2012 Jun 15.
Epidemiology studies indicate that exposure to endocrine disruptors during developmental "window" contributes to adipogenesis and the development of obesity. Implication of endocrine disruptor such as diethylstilbestrol (DES) on adipose tissue development has been poorly investigated. Here we evaluated the effects of DES on adipocyte differentiation in vitro and in vivo, and explored potential mechanism involved in its action. DES induced 3T3-L1 preadipocyte differentiation in a dose-dependent manner, and activated the expression of estrogen receptor (ER) and peroxisome proliferator-acivated receptor (PPAR) γ as well as its target genes required for adipogenesis in vitro. ER mediated the enhancement of DES-induced PPARγ activity. Moreover, DES perturbed key regulators of adipogenesis and lipogenic pathway in vivo. In utero exposure to low dose of DES significantly increased body weight, liver weight and fat mass in female offspring at postnatal day (PND) 60. In addition, serum triglyceride and glucose levels were also significantly elevated. These results suggest that perinatal exposure to DES may be expected to increase the incidence of obesity in a sex-dependent manner and can act as a potential chemical stressor for obesity and obesity-related disorders.
流行病学研究表明，在发育“窗口”期间暴露于内分泌干扰物会导致脂肪生成和肥胖的发展。内分泌干扰物（如己烯雌酚[DES]）对脂肪组织发育的影响尚未得到充分研究。在这里，我们评估了 DES 对体外和体内脂肪细胞分化的影响，并探讨了其作用涉及的潜在机制。DES 以剂量依赖性方式诱导 3T3-L1 前体脂肪细胞分化，并在体外激活雌激素受体（ER）和过氧化物酶体增殖物激活受体（PPAR）γ的表达及其脂肪生成所需的靶基因。ER 介导了 DES 诱导的 PPARγ 活性的增强。此外，DES 在体内扰乱了脂肪生成和脂生成途径的关键调节剂。围产期暴露于低剂量 DES 可显著增加雌性后代在产后第 60 天的体重、肝重和脂肪量。此外，血清甘油三酯和葡萄糖水平也显著升高。这些结果表明，围产期暴露于 DES 可能会以性别依赖的方式增加肥胖的发生率，并可能成为肥胖和肥胖相关疾病的潜在化学应激源。
