酪蛋白巨肽对食欲的影响及作用机理研究

项目名称： 酪蛋白巨肽对食欲的影响及作用机理研究

项目编号： No.31301458

项目类型： 青年科学基金项目

立项/批准年度： 2014

项目学科： 农业科学

项目作者： 张宁宁

作者单位： 福建农林大学

项目金额： 23万元

中文摘要： 肥胖症及其引发的一系列健康问题，引起人们的广泛关注。摄食调控是防止肥胖症发生的最安全、有效的方法。大量研究表明，高蛋白膳食对于人体维持健康体重具有益处。酪蛋白巨肽（CMP）是κ-酪蛋白C端的64个氨基酸所组成的多肽。人体实验证实CMP能刺激胆囊收缩素（cholecystokinin，CCK）分泌。研究表明内源和外源性CCK均能抑制食欲。因此，推测CMP可能对摄食和饱腹感调节具有影响作用。本项目在制备CMP的基础上，借助大鼠摄食实验、胰蛋白酶活性抑制实验、CCK受体拮抗剂-地伐西匹实验、CMP在体内的代谢研究、及STC-1细胞分泌CCK等实验研究，尝试解决五个问题：1）确定CMP是否影响大鼠食欲；2）如果影响食欲，研究其潜在作用机制；3）建立CMP在体内的代谢动力学模型；4）建立糖基化酪蛋白巨肽与非糖基化酪蛋白巨肽的分离纯化方法；5）探索CMP刺激CCK分泌的胞内信号途径。

中文关键词： 酪蛋白巨肽；食欲；饱腹激素；作用机制；代谢组学

英文摘要： Health consequences of overweight and obesity include increased risk for heart disease, diabetes, hypertension and certain cancers. And lots of things have been done to halt its rampant progression. Dietary intervention is the safest and most practical approach to controlling the obesity epidemic. Evidence has been accumulated indicating that protein is beneficial to healthy body weight in human subjects. The 64 C-terminal amino acids of κ-casein, known as caseinomacropeptide (CMP), are formed by chymosin (or pepsin) cleavage of κ-casein between Phe105-Met106 during the manufacture of cheese. CMP has shown to stimulate CCK release in humans. And both endogenous and exogenous CCK suppresses appetite. Therefore, the hypothesis that CMP might play a role in appetite and satiety arises. The present study has tried to address 5 questions by in vivo and in vitro experiments: 1) When provide alone, does CMP influence appetite? 2) If it does have effect on appetite, can this be explained by stimulating CCK release? 3) Metabolic kinetcs of CMP in rats after infusion. 4) Separation of a glycosylated and non-glycosylated fraction of CMP using anion-exchange chromatography. 5) Does CMP increase CCK level by directly reacting on CCK-secreting cells

英文关键词： caseinomacropeptide；appetite；satiety signals；mechanism of action；metabonomics