我们的前期研究发现,非酒精性脂肪肝（NAFLD）发病机制中所涉及的肝脏脂代谢紊乱和胰岛素抵抗与转甲基异常密切相关。ADP-PPARα信号通路中脂肪合成与代谢相关基因表达异常可引起肝脏脂肪酸合成增加、转运障碍以及β氧化受阻，从而促进脂质在肝脏的沉积，与NAFLD的发生密切相关。甲基供体不仅通过转甲基作用降低同型半胱氨酸（Hcy）而增加ADP水平，而且通过影响ADP-PPARα通路相关基因的甲基化程度来调节肝脏脂质代谢从而缓解肝脏脂质沉积，但确切机制未见相关的报导。本研究拟用NAFLD病例-对照研究和不同甲基供体水平对NAFLD动物模型干预实验，采用亚硫酸氢盐测序（BSP）方法和HPLC-MS/MS分析技术，探讨甲基供体与NAFLD的关联性及其对ADP-PPARα信号通路脂代谢调节基因甲基化的影响。本研究从表观遗传学的机制探讨脂代谢基因甲基化状态与NAFLD的关系具有创新性。

Lipid metabolism disorder and insulin resistance involved in the pathogenesis of non alcohol fatty liver disease (NAFLD) are closely related with abnormal transmethylation in the liver. Altered expression of lipid metabolism-related genes in ADP-PPARα pathyway are closely correlated with NAFLD because this changes can contribute to the increased synthesis but decreased transport and β-oxidation of triglyceride, thereby promoting lipid deposit in the liver. Methyl donors are able to decrease the hcy concentration by transmethylation pathway, so as to increase the ADP level. However, whether methyl donors alleviating the lipid deposit by mediating the promoter methylation level of genes involved in ADP-PPARα signal pathway is still unknown.In present study,we use BSP and HPLC-MS/MS method,via a case-control study and the NAFLD animal moedel, to discuss the association between methyl donors and NAFLD, and the effect of methyl donors on promoter methylation level of lipid metabolism-related genes in ADP-PPARα signal pathway. Our research on the relationship between methylation state and NAFLD via epigenetic mechanism are strikingly meaningful and creative.