Studies on relationship between environmental endocrine disrupting chemicals and development of hyperlipidaemia

1.以小鼠成纤维细胞系3T3-L1为研究对象，观察了双酚A对脂蛋白脂酶(LPL)表达和三酰甘油(TG)积累的影响。双酚A具有诱导3T3-L1成纤维细胞分化为脂肪细胞的能力。BPA分化的培养细胞用INS单独处理，INS和EPA结合使用。在INS和BPA联合作用下，脂肪细胞LPL活性和TG积累量均高于单独INS处理组，提示BPA具有促进INS诱导的脂肪细胞成熟的作用。双酚A二乙酸酯和双酚A二(氯甲酸酯)有类似的作用，但不是双酚A二缩水甘油醚，但效力不如双酚A。这些结果表明，人类长期暴露于BPA及其相关化学物质可能会导致肥胖的发生。2.在完全分化的3T3-L1细胞中，观察了4-壬基酚(NP)和4-叔辛基酚(OP)对LPL表达和TG积聚的影响。NP可抑制LPL mRNA的表达，进而显著降低LPL活性。此外，NP还抑制了TG的积累。OP也有类似的作用，但作用不如NP。这些结果表明，人类长期接触烷基酚可能会导致高脂血症的发生。3.雌性小鼠(4周大)被允许自由饮用含有双酚A和自来水的食物。服用1μg双酚A/g饲料的小鼠的血糖水平高于对照组，但并不显著。对照组和双酚A饲料喂养的小鼠附睾脂肪组织重量和血脂水平无明显差异。

1.Using a cell line of mouse fibroblasts, 3T3-L1 fibroblasts, we examined the effect of bisphenol A on expression of lipoprotein lipase (LPL) and triacyiglycerol (TG) accumulation. BPA had the ability to induce the differentiation of 3T3-L1 fibroblasts into adipocytes. The BPA-differentiated cultures were treated with either INS alone a combination of INS and EPA. Expression of LPL activity and TG accumulation in the cultures treated with a combination of INS and BPA were higher than those in the cultures treated with INS alone, indicating that BPA had the ability to enhance INS-induced adipocyte maturation. Bisphenol A diacetate and bisphenol A bis(chloroformate), but not bisphenol A diglycidyl ether, had a similar effect but was less potent than BPA. These results suggest that chronic exposure of humans to BPA and BPA-related chemicals may induce development of obesity.2.The effect of 4-nonylphenol (NP) and 4-tert-octylphenol (OP) on expression of LPL and TG accumulation were examined in fully differentiated 3T3-L1 cells. NP inhibited expression of LPL mRNA, and subsequently lowered markedly LPL activity. In addition, NP suppressed TG accumulation. OP had a similar effect but was less potent than NP. These results suggest that chronic exposure of humans to alkylphenols may induce development of hyperlipidaemia.3.Male mice (4 weeks old) were allowed free access to a diet containing BPA and tap water. Plasma glucose level of mice administered a diet containing 1μg BPA/g diet was higher, but not significantly, than that of mice administered a control diet. There were no difference in epididymal adipose tissue weight and plasma lipid levels between control diet-fed mice and BPA-containing diet-fed mice.