苏氨酸介导STAT蛋白磷酸化调控肉鸭肝脏脂质沉积的分子机制

营养代谢失调引起的脂质代谢紊乱会影响家禽生长和健康。研究发现，苏氨酸在调节脂质代谢中起着重要作用，但其具体分子机制还不清楚。申请人前期研究发现，饲粮缺乏苏氨酸可增加肉鸭肝脏脂质沉积，并且参与JAK-STAT通路的信号转导。已有研究表明，JAK-STAT通路中STAT蛋白磷酸化调节脂质代谢。提示苏氨酸可能通过STAT蛋白磷酸化介导调控肉鸭肝脏脂质沉积。因此，本项目首先探明苏氨酸对肉鸭肝脏脂质沉积和STAT蛋白磷酸化水平的影响，采用磷酸化蛋白组学明确STAT蛋白磷酸化的主要亚型（STATn）及其磷酸化位点；并在体外验证苏氨酸对肉鸭肝脏原代细胞脂质沉积和STATn蛋白磷酸化水平的影响；最后，利用定点突变技术，验证STATn去磷酸化后苏氨酸对肉鸭肝脏原代细胞脂质沉积的影响。研究旨在揭示苏氨酸通过STATn磷酸化调控肉鸭肝脏脂质沉积的分子机制，为肉鸭生产中营养性预防肝脏脂质代谢紊乱提供理论依据。

The lipid metabolism disorder caused by nutrient metabolism disorder might affect the growth and health of poultry. Resent study showed that threonine plays an important role in lipid metabolism in poultry. Whereas, its molecular mechanism remains unclear. Based on our previous findings, dietary threonine deficiency increased hepatic lipids deposition of ducks, and influenced signal transduction of JAK-STAT signaling pathway. Previous studies showed that STAT protein phosphorylation in JAK-STAT signaling pathway regulated lipid metabolism. Which indicated that dietary threonine might regulate hepatic lipid deposition of ducks via mediating STAT phosphorylation. So, the first study will be conducted to determine the effects of dietary threonine on hepatic lipids deposition and STAT phosphorylation, and to screen the subtype of STAT phosphorylation (STATn) and its phosphorylation sites with phosphoproteomics. Then, another study will be conducted to verify the roles of threonine on lipid deposition and STATn phosphorylation of hepatocyte in vitro. Finally, to reveal the effects of threonine on hepatocyte lipids deposition under STATn dephosphorylation with site-directed mutation technique. The results of present study will clarify that the molecular mechanism of threonine regulation on hepatic lipid deposition via mediating STATn phosphorylation in ducks, which will provide a theoretical basis for nutritional prevention of hepatic lipid metabolism disorders in duck production.