牡蛎源肽基于抑制胰脂肪酶调控脂肪酸吸收与脂代谢的机制研究

发掘具有降低脂肪摄入作用的营养成分是功能性食品领域关注的热点。与神经受体干预相比，对胰脂肪酶具有抑制活性的成分在安全性和可及性上具有明显优势。项目前期建立了模拟胃肠道消化的牡蛎源肽文库，且发现牡蛎源肽可缓解小鼠肥胖进程，并由分子模拟筛选了具有潜在抑制胰脂肪酶活性的多肽序列，然而多肽体内抑制胰脂肪酶活性介导的脂肪酸吸收及其脂质代谢关联的作用机制尚未阐明。本项目拟通过分子模拟结合体外抑制实验明确抑制胰脂肪酶活性的牡蛎源肽序列；考察肽在胃肠道中发挥作用的稳定性及作用浓度，从分子互作角度揭示其对胰脂肪酶的抑制机制；采用高脂饮食模型小鼠灌胃验证牡蛎源肽对脂肪酸吸收的影响，并通过脂质组学方法深入探究其对脂质代谢的影响及其机理。项目旨在从胰脂肪酶活性抑制角度系统揭示牡蛎源肽调节脂肪酸吸收与脂代谢的分子机制。项目将丰富和完善多肽维持能量代谢平衡机理，为降低脂肪吸收功能食品开发提供理论指导。

The discovery of nutrients that can reduce fat intake is a hot topic in the functional food field. Compared with neuroreceptor interventions, pancreatic lipase inhibitors have a significant safety and accessibility advantages. The early stage of the project has established the oyster peptide library by simulated gastrointestinal digestion and found that oyster-derived peptides can alleviate the process of obese mice, and the potential inhibition of pancreatic lipase activity of peptide sequence has been screened out by molecular simulation. However, the mechanism by which peptides inhibit fatty acid uptake mediated by pancreatic lipase activity and their association with lipid metabolism has not been elucidated. This project intends to identify the sequence of oyster source peptides that inhibit pancreatic lipase activity through molecular simulation combined with in vitro inhibition experiments. The stability and concentration of peptides in the gastrointestinal tract will be investigated to reveal the inhibitory mechanism of peptides on pancreatic lipase from the perspective of molecular interaction. The effect of oyster peptides on fatty acid absorption will be verified by intragastric administration of high-fat diet model mice, and the effect of oyster peptides on lipid metabolism and its mechanism will be further explored by lipidomics. This project aims to systematically reveal the molecular mechanism of oyster peptides regulating fatty acid absorption and lipid metabolism from the perspective of pancreatic lipase activity inhibition. The project will enrich and improve the mechanism of peptides to maintain the balance of energy metabolism, and provide theoretical guidance for the development of food with the function of reducing fat absorption.