补充甘氨酸对非酒精性脂肪肝的多重影响与代谢网络机制的研究

非酒精性脂肪肝（NAFLD）的患病率正在急剧上升，严重危害了人类健康。NAFLD的病理基础是糖脂代谢紊乱、胰岛素抵抗、炎症与氧化应激，因此阻断以上多种致病机制是防治的关键。我们的meta分析与前期研究均发现肥胖、糖尿病、代谢综合征以及NAFLD均存在氨基酸代谢紊乱，且血液中甘氨酸含量均显著降低。甘氨酸是人类重要的氨基酸，可用于谷胱甘肽、血红素、肌酸的生物合成，并具有调节代谢、氧化、炎症及保护肝脏等作用。因此本课题拟利用人群干预试验、动物模型系统研究补充甘氨酸是否能改善NAFLD个体的肝脏脂肪含量、糖-脂-氨基酸代谢紊乱、炎症、氧化应激水平；通过动物实验研究其分子生物学机制；利用代谢组学技术，寻找补充甘氨酸的生物标志物，并探讨甘氨酸代谢与NAFLD的内在联系；从人体、动物和代谢产物三个层面深入探讨甘氨酸发挥作用的分子机制与代谢途径,为NAFLD的防治提供依据。

The prevalence of non-alcoholic fatty liver disease (NAFLD) is rising rapidly, serious harm to human health. The pathological basis of NAFLD is glucolipid metabolic disorders, insulin resistance, inflammation and oxidative stress. Thus, blocking above pathogenesis is the key point to prevent NAFLD. Our meta-analysis and previous study found that amino acid metabolism disorders present in patients with obesity, diabetes, metabolic syndrome, and NAFLD, and the circulating glycine levels were significantly lower in all these diseases. Glycine is an important human amino acid, which could be used for biosynthesizing glutathione, heme and creatine, regulating metabolism, oxidation and inflammation, and protecting the liver injury. Thus, this project intends to use a human intervention trial and animal model study to confirm whether glycine can improve liver fat content, glucose-lipid-amino acid metabolism disorders, inflammation and oxidative stress in NAFLD subjects; using animal studies to elucidate the molecular mechanisms of glycine; using metabonomics technology, to find biomarkers of glycine supplement and the immanent connection between glycine metabolism and NAFLD; from human, animal and metabolites of 3 aspects, we would explore the molecular mechanisms and metabolic pathways of the roles of glycine. This study would provide significant basis for preventing and curing for NAFLD.