Insulin resistance and dysregulated lipid meta- bolism are major causes of type 2 diabetes. Insulin and inflam- matory signal pathways play key roles in insulin resistance and fat accumulation. Specifically, adapter p...Insulin resistance and dysregulated lipid meta- bolism are major causes of type 2 diabetes. Insulin and inflam- matory signal pathways play key roles in insulin resistance and fat accumulation. Specifically, adapter proteins transduce sig- nals from insulin or cytokine receptors to the downstream pathways and may contribute to insulin resistance and disor- dered lipid metabolism in obesity and type 2 diabetes. Here, the recent advances in understanding the roles of adapter proteins in insulin resistance and lipid homeostasis are discussed.展开更多
文摘目的研究阿托伐他汀对脂多糖(Lipopolysaccharide,LPS)诱导的小鼠巨噬细胞RAW264.7脂代谢相关蛋白表达及胆固醇流出的影响,并探讨其可能的作用机制。方法用不同浓度LPS刺激RAW264.7细胞,在不同时间点以Western blot方法检测脂质代谢相关蛋白ABCA1、ABCG1、SR-B1、PCSK9和LDLR的表达,从而确定LPS最佳作用浓度和时间。Western blot检测不同浓度阿托伐他汀对50ng/m L LPS诱导的上述脂代谢相关蛋白表达变化的影响,激光共聚焦观察BODIPY荧光标记的胆固醇流出状况。结果在RAW264.7细胞中,LPS呈浓度和时间依赖性抑制ABCA1、ABCG1、SR-B1和LDLR蛋白的表达,对PCSK9蛋白表达无显著影响。阿托伐他汀浓度依赖性的上调LPS诱导的ABCA1、ABCG1、SR-B1和LDLR蛋白表达降低,上调PCSK9蛋白的表达,从而增加胆固醇流出,减少细胞内胆固醇聚集。结论阿托伐他汀干预能够改善LPS引起的脂代谢相关蛋白表达并增强胆固醇流出,该作用可能是其抗动脉粥样硬化机制之一。
基金Acknowledgements This work was supported by the Changbai Mountain Scholars Program of Jilin Province 2013046 （to Z. C.）, the Jilin Talent Development Foundation 111860000 （to Z. C.）, the National Natural Science Foundation of China Grant 31500957 （to Z. C.）, and the startup funds from Northeast Normal University 120401204 （to Z. C.）. I thank Dr. Mark J. Canet （University of Michigan） for editing this manuscript. I also thank lab members （Xinzhi Li, Wangshu Qin, Linna Jia, Sha Li, Xiaomeng Ren, Xue Dong, and Jiana Liu） at Northeast Normal University for helpful discussion. I apologize to colleagues whose relevant work could not be cited here due to space limitation.
文摘Insulin resistance and dysregulated lipid meta- bolism are major causes of type 2 diabetes. Insulin and inflam- matory signal pathways play key roles in insulin resistance and fat accumulation. Specifically, adapter proteins transduce sig- nals from insulin or cytokine receptors to the downstream pathways and may contribute to insulin resistance and disor- dered lipid metabolism in obesity and type 2 diabetes. Here, the recent advances in understanding the roles of adapter proteins in insulin resistance and lipid homeostasis are discussed.
