非酒精性脂肪性肝病（non-alcoholic fatty liver disease, NAFLD）患病率逐年增长，已成为危害人群健康的重大临床和社会问题，目前无有效的针对性治疗方案。胆汁酸代谢异常贯穿代谢综合征的发生发展并有可能成为脂代谢紊乱潜在的干预靶点。申请人由以减肥为主要目标的胃绕道旁路术（RYGB）术后患者血浆胆汁酸明显升高且与代谢改善明确相关这一临床现象出发，基于前期研究已证实的“肠道胆汁酸-FXR代谢轴参与NAFLD的肝脏脂质代谢”的结果，将肠道-肝脏作为代谢的“整体”单元，以肠道胆汁酸-FXR代谢轴的功能为切入点、以两种NAFLD动物模型行RYGB手术为主要观察对象、以代谢组学为研究方法分析胆汁酸组学改变及其对肝脏脂质代谢的作用，利用全身和肠道FXR敲除小鼠为工具进一步探索肠道胆汁酸-FXR代谢轴影响肝脏脂质代谢稳态调节的可能机制，为靶向药物开发提供理论依据。

Nonalcoholic fatty liver disease (NAFLD) has a increasing prevalence rate world wide and there has no precision method nor drugs could be the targeted therapy, NALFD became a major medical and social problem. Previous studies suggest that bile acids metabolism disorder occurs the duration of the metabolic syndrome and might be novel intervention targets of the lipids metabolism disorders, there has no systematic studies on whether bile acid could improve hepatic lipids metabolism. In clinical, we find those obesity patients who underwent Roux en Y operation has a plasma bile acid level increasing and a metabolic improvement far before the body weight loss, hints a intestine bile acids and hepatic lipids has a crosstalke. In our project, we will taking gut and liver as “one” lipids metabolic unit, using the metabonomics methods to uncover the role of intestinal bile acids-FXR metabolism axis using RYGB surgery model, FXR global and intestinal tissue specific knock out mouse would used in our program to figure out the possible mechanisms of intestinal bile acids-FXR metabolism axis’s function in hepatic lipids metabolism homostasis.