肝脏脂滴异常聚集是NAFLD发生的重要机制。研究发现，槲皮素可明显减轻小鼠和大鼠的肝脂肪变，可能改善人群的血脂水平；但其治疗NAFLD的临床疗效未明确。我们预实验发现，槲皮素干预可减轻棕榈酸诱导的人正常HHL5肝细胞的脂滴聚集，并升高脂滴分解中关键酶脂肪甘油三酯脂肪酶（ATGL）的共激活因子比较基因识别因子58（CGI58）的蛋白表达，但不影响ATGL表达。因此，我们提出研究假说：槲皮素通过调节ATGL/CGI58及其相互作用，促进脂滴分解，从而改善肝细胞脂滴聚集；槲皮素可改善NAFLD患者的肝脏脂肪沉积、肝功能及糖脂水平。本项目应用ATGL/CGI58 siRNA及表达载体质粒转染HHL5细胞，深入研究ATGL/CGI58在槲皮素促进肝细胞脂滴分解中的作用及机制；开展随机双盲临床试验，观察槲皮素改善NAFLD患者的肝脏脂肪沉积等临床效应，结果将为研究治疗NAFLD的新型药物提供科学依据。

Abnormal aggregation of liver lipid droplets is an important mechanism for the development of NAFLD. Many studies found that quercetin can significantly reduce hepatic steatosis in mice and rats, and may improve blood lipid levels in human. However, its clinical efficacy of quercetin on the treatment of NAFLD is unclear. Our previous found that quercetin intervention can alleviate lipolysis in normal human HHL5 hepatocytes induced by palmitic acid, and increase protein expression of comparative gene identification-58 (CGI58) which is the co-activator of adipose triglycerides lipase (ATGL), the key enzyme in lipid droplets catabolism, but does not affect protein expression of ATGL. Thus, we propose a hypothesis that quercetin can promote the deposition of lipid droplets by regulating ATGL/CGI58 and its interactions, thereby improving the accumulation of lipid droplets in hepatocytes; quercetin can improve liver fat deposition, liver function and the levels of blood glucose and lipids in patients with NAFLD. This project will use ATGL/CGI58 siRNA and expression vector plasmid to transfect HHL5 cells to study the role and mechanism of ATGL/CGI58 in the effect of quercetin on promoting hepatocyte lipid droplet decomposition; and conduct a randomized double-blind clinical trial to observe the clinical effects of quercetin supplement on liver fatty deposition in patients with NAFLD. The current study will provide a scientific basis for the study of new drugs for the treatment of NAFLD.