谷糠多酚对香豆酸和阿魏酸协同调节GLP-1改善糖脂代谢紊乱的分子机制

谷糠富含植物多酚，对人体代谢平衡具有重要调控作用，是日益增多的糖脂代谢紊乱人群的理想膳食补充剂。胰高血糖素样肽-1（GLP-1）是肠促胰岛素的一种，能够以葡萄糖依赖的方式促进胰岛素分泌进而调节糖脂代谢。我们前期研究发现，谷糠多酚对香豆酸和阿魏酸能够协同作用于GLP-1，促进餐后胰岛素响应进而改善糖脂代谢紊乱，其中对香豆酸通过下调GRP78表达促进L细胞的GLP-1分泌，阿魏酸可与GLP-1直接结合提高其半衰期。本项目拟采用DNA免疫沉淀和质谱技术筛选对香豆酸调控的GRP78上游转录因子X；采用荧光光谱、分子对接以及基因工程等手段探究阿魏酸与GLP-1的结合方式和结合位点；利用小鼠高糖高脂饮食模型验证上述机制。本项目的顺利实施将阐明对香豆酸和阿魏酸促进GLP-1分泌并提高其半衰期，从而改善糖脂代谢紊乱的协同机制，为谷糠在糖脂代谢紊乱人群膳食中的应用提供科学依据，推动全谷物资源的深度挖掘利用。

Foxtail millet bran is rich in polyphenols, which play important role in regulating the body's metabolic balance, and are preferred dietary supplement for an increasing number of people with disorders of glucose and lipid metabolism. Glucagon-like peptide 1 (GLP-1) is a type of incretin hormones that promotes insulin secretion in a glucose-dependent manner, and regulates glucose and lipid metabolism. Previous research in this project found that p-coumaric acid and ferulic acid in Foxtail millet bran synergistically promoted postprandial insulin response and improved glucose and lipid metabolism disorders through GLP-1. P-coumaric acid promoted GLP-1 secretion of L cell by downregulating GRP78 expression, while ferulic acid direct bound with GLP-1 to increase its half-life. In this project, DNA pull-down and mass spectrometry will be adopted to screen the upstream transcription factor of GRP78 that is regulated by p-coumaric acid; The technology combined fluorescence spectroscopy, molecular docking and genetic engineering will be employed to explore the binding mode and binding sites of ferulic acid and GLP-1; The above mechanism will be verified using a mouse model induced by high-sugar and high-fat diets. The successful implementation of this project will clarify the synergistic mechanism of p-coumaric acid and ferulic acid in foxtail millet bran by promoting GLP-1 secretion and increasing its half-life, thereby improving glucose and lipid metabolism disorders. It will provide a scientific basis for the application of foxtail millet bran in nutritional diet for people with metabolic disorders, and promote the in-depth development of grain resources.