我们之前的研究表明，非酒精性脂肪肝病人肝脏脂滴上17-beta-羟固醇脱氢酶-13(17β-HSD13)的含量显著上升，过表达该蛋白会引起小鼠肝脏发生明显的脂肪变性。为了进一步研究17β-HSD13如何影响肝脏中脂滴的形态和功能，我们将分别构建高表达和敲除17β-HSD13的细胞株和小鼠，检测脂滴的形态变化，鉴定脂滴上的差异分子，然后探索差异分子对脂滴形态变化的作用。为寻找引起这些分子差异的原因，我们将检测17β-HSD13的酶活性及其催化产物，鉴定17β-HSD13对脂滴的影响是否由其产物介导，寻找产物下游的核受体及其调控的脂代谢相关基因。我们还将通过17β-HSD13截短体的表达和人工脂滴体系，研究该蛋白的其他特性及相互作用蛋白对脂滴的影响。这一研究将揭示17β-HSD13如何影响非酒精性脂肪肝的发生和发展，并有助于研究其他HSD家族蛋白在脂滴上的功能。

Our previous work identified that the expression of 17-beta-hydroxysteroid dehydrogenase 13 (17β-HSD13) is increased dramatically on non-alcoholic fatty liver disease (NAFLD) patient liver LDs and overexpression of 17β-HSD13 causes obvious liver steatosis in mice. To study how 17β-HSD13 affects the LD morphology and function in liver, we will regulate the expression level of 17β-HSD13 in mouse liver and hepatic cells, and then detect the LD morphology and identify the different molecules between the LDs. In order to find reasons that cause the differences, we will then determine if the enzyme activity and product of 17β-HSD13 mediate LD morphological change, and then find the nuclear receptor for the product and the downstream genes related to lipid metabolism. We also will study whether 17β-HSD13 functions as a structure protein or a component of a protein complex that play a role to regulate LDs by expression of truncated proteins and artificial LD system. This study will elucidate the mechanism how 17β-HSD13 affects the development of NAFLD and provide clues for the functional study of other HSD proteins on LDs.