与哺乳动物非酒精性脂肪肝病（NAFLD）常伴有炎症不同，鹅肥肝可能存在保护机制使其在高度脂肪变性时不发生炎症。已知胆胺可通过生成CDP-胆碱参与神经酰胺/鞘氨醇的转化，而神经酰胺/鞘氨醇可促进NAFLD中炎症的发生。课题组前期研究发现鹅肥肝中胆胺和鞘氨醇的含量显著低于对照组。我们推测胆胺通过促进神经酰胺/鞘氨醇转化为鞘磷脂抑制炎症的发生。本项目拟在鹅原代肝细胞中敲低胆胺/胆碱激酶以及在棕榈酸诱导的细胞炎症模型中添加胆胺，明晰胆胺对炎症反应的调节作用；敲低细胞中促神经酰胺/鞘氨醇转化为鞘磷脂的关键酶，明晰胆胺抑制炎症的机制；在活体鹅中敲低胆胺/胆碱激酶表达，研究胆胺使鹅肥肝（非炎症模型）免于炎症反应的保护机制；在高脂诱导的小鼠脂肪肝（炎症模型）中添加胆胺，验证胆胺对炎症反应的抑制作用。研究结果不仅有助于阐明鹅肥肝具有的独特保护机制，而且可为人类和其他动物脂肪肝的研究提供参考。

Unlike mammalian non-alcoholic fatty liver disease (NAFLD), which is often accompanied by inflammation, goose fatty liver has a mechanism to protect it from severe steatosis-associated inflammation. It is known that cholamine is involved in the transformation of ceramide/sphingosine by producing CDP-choline, while these sphingolipids can promote the occurrence of inflammation in NAFLD. Consistently, our preliminary data showed that the contents of cholamine and sphingosine in goose fatty liver were both significantly lower than normal. We thus speculate that cholamine may inhibit the occurrence of inflammation in goose fatty liver by promoting the transformation of ceramide/sphingosine into sphingomyelin. This project intends to knock down cholamine/choline kinases in goose primary hepatocytes and add cholamine to palmitic acid-induced inflammation model to clarify the regulatory effect of cholamine on inflammation; knock down the key enzymes that promote conversion from ceramide/sphingosine to sphingomyelin in the cell to determine the mechanism of cholamine inhibiting inflammation; knock down the expression of cholamine/choline kinases in living geese to investigate the protective mechanism of cholamine against inflammation in goose fatty liver (non-inflammatory model); add cholamine to the high-fat diet induced NAFLD model of mice to verify the effects of cholamine on inflammation. The results from this project will not only help to elucidate the unique protective mechanism of goose fatty liver, but also provide reference for the research of human and other animal fatty liver.