食品危害物氯虫苯甲酰胺通过激活FGF10通路促进脂肪细胞分化和脂肪积累的机制研究

新型双酰胺类杀虫剂的广泛使用威胁我国的食品安全，氯虫苯甲酰胺是双酰胺类杀虫剂的典型代表，它能够诱导脂肪细胞积累过多的脂肪，然而其作用机制尚不明确。本项目拟探究氯虫苯甲酰胺诱导脂肪积累的分子机制。前期转录组测序和小分子干扰RNA实验发现成纤维细胞生长因子（FGF10）是调控氯虫苯甲酰胺诱导脂肪积累的关键蛋白。本项目拟采用3T3-L1脂肪细胞与小鼠模型，结合qRT-PCR，免疫印迹，小分子干扰RNA等技术研究FGF10参与氯虫苯甲酰胺促进体外脂肪细胞分化及体内脂肪积累的过程，以及FGF10对下游环磷酸腺苷反应结合蛋白 （CREB）和磷脂酰肌醇3-激酶（PI3K）通路的影响，探明FGF10介导氯虫苯甲酰胺促进脂肪积累的分子机制。研究结果将阐明氯虫苯甲酰胺诱导脂类代谢异常的作用机理，为研究此类杀虫剂与糖脂代谢异常的关系提供新思路，为食品安全风险评估提供可靠的理论支持。

The widespread use of new-type diamide insecticides threatens the food safety of our country. Chlorantraniliprole is a typical representative of diamide insecticides, which can induce fat cells to accumulate excess fat. However, the mechanism of its action is not clear. This project intends to explore the molecular mechanism of lipid accumulation induced by chlorantraniliprole. Previous RNA- sequencing and siRNA analysis revealed that fibroblast growth factor 10 (FGF10) is likely to be a key maker that regulates chlorantraniliprole-induced adipogenesis. Thus, the effect of chlorantraniliprole on FGF10 and its downstream cAMP-response-element-binding protein (CREB) and phosphoinositide 3-kinase (PI3K) pathways will be studied by using 3T3-L1 adipocytes and mouse models together with other technologies, including RT-PCR, immunoblotting, siRNA, etc. The results will clarify the mechanism of lipid accumulation induced by chlorantraniliprole, produce new ideas for the study of the relationship between these pesticides and impaired glycolipid metabolism, and provide reliable theoretical support for food safety risk assessment.