非酒精性脂肪肝是非酒精性脂肪肝病的标志，可发展成严重的肝病，近年来发病率猛增，严重危害国民健康。脂肪肝属痰湿范畴，与脾胃功能失调密切相关。生（干）姜为最常用的中药和调味料之一，主要取其调理脾胃、治疗痰湿的功效，其防治脂肪肝的疗效已为现代研究所证实。但其作用机制尚不清楚。我们最新研究结果证明，调节糖脂代谢的关键因子――碳水化合物反应元件结合蛋白(ChREBP)是姜提取物改善脂肪肝的重要靶标。基于此重要发现，本项目采用模拟人类非酒精性脂肪肝的细胞和动物模型，通过观察在"核转位"和"DNA结合／转录活性的激活"两个水平上对ChREBP磷酸化、糖基化，及二者的"阴阳"关系平衡的调节作用，从蛋白质修饰这一新视点，进一步探讨姜提取物及其主要活性成分对肝ChREBP的分子调控。此项目的顺利实施将为从生（干）姜中开发新型防治脂肪肝的高效低毒药物提供分子药理学依据，并有助于揭示其调理脾胃、防治痰湿证的本质。

Fatty liver is the hallmark of nonalcoholic fatty liver disease, which has become an important public health problem due to its high prevalence, potential progression to severe liver disease, and association with the metabolic syndrome, diabetes and cardiometabolic abnormalities. Fatty liver belongs to "Phlegm-dampness" due to dysfunction of spleen and stomach in TCM. Ginger is one of the most commonly used spices and medicinal plants around the world. Ginger is attributed to spleen and stomach channels, functions as a spleen-stomach-regulating herb, and widely used in the formulas for Phlegm-dampness syndrome in TCM. It has been well demonstrated that ginger improves dietary-induced fatty liver in rodents. However, the molecular mechanisms underlying the anti-steatotic effect of ginger are still unknown. Recently, Our research team has found that ginger improves fructose overconsumption-induced fatty liver via the hepatic pathway of ChREBP, an attractive molecular target for lipid-lowering therapies in obesity and diabetes. Based on this important finding, we in the proposed project will investigate how ginger and its prominent active components regulate hepatic ChREBP O-GlcNAcylation, phosphorylation and their 'Yin-Yang' relationship at "nuclear translocation" and "DNA banding/transcription activities" level using the well-accepted rat model of fructose-induced fatty liver and the specific HepG2 cell model of fructose-activated ChREBP. The findings of this project will not only supply with molecular pharmacological basis for developing new potent medicine for fatty liver from ginger, but also provide new insight into the spleen and stomach-regulating property of ginger in the prevention and treatment of Phlegm-dampness syndrome. Thus, this project has novelty and significance.