海参岩藻聚糖硫酸酯通过调节肠道CD36脂质代谢通路防治肥胖的作用

Obesity has reached epidemic proportions globally and become a major threat to human health. Fucoidan from Pearsonothuria graeffei with well-repetitive structure has been proved to be powerful to control hyperlipidemia and obesity in obese mice while the mechanism is unclear. In the present study, fuc-Pg is used as research object to explore whether it can occupy the binding site of fatty acid in CD36 or not, thus regulating enterocyte CD36-lipometabolism pathway. Firstly, surface plasmon resonance (SPR) is used to confirm that whether fuc-Pg can interact with CD36 protein molecule or not. Then, wild-type mice and CD36-gene-knockout mice are administrated with fluorescence indicator of fuc-Pg to the possible of fuc-Pg binding to CD36. Based on above experiments, we use obese mice induced by high-fat and high-sugar to investigate the lipid transport pathway and inflammatory pathways modulating by CD36. The long-term effects of fuc-Pg on enterocyte CD36-lipometabolism pathway are studied by measuring the expression of related proteins and their mRNA levels, such as, ApoB48, NF-κB, etc. The present study will provide theoretical basis for the mechanism of controlling obesity of fucoidan from sea cucumbers.

肥胖已经成为全球性疾病，危害机体健康。菲律宾刺参岩藻聚糖硫酸酯（fuc-Pg）是一种活性具有重复序列结构的硫酸多糖且对肥胖小鼠具有良好的降脂减肥效果，但作用机制尚不明确。本课题以fuc-Pg为研究对象，探究其能否与小肠绒毛顶端CD36跨膜蛋白结合，与膳食脂肪酸形成竞争性抑制，从而调控小肠上皮细胞脂质代谢信号通路。首先通过等离子共振技术（SPR）初步确定fuc-Pg能否与CD36蛋白分子发生相互作用。其次，利用fuc-Pg荧光标记物探究其在野生型和CD36基因敲除小鼠肠道内能否与CD36结合。在此基础上，利用高脂高糖饲料诱导肥胖小鼠模型，以CD36调控的脂质转运通路和炎症通路为切入点，探究长期摄入fuc-Pg对肠上皮细胞ApoB48、NF-κB等相关蛋白的表达及其mRNA水平的影响，阐明fuc-Pg对肠上皮细胞脂质代谢通路的影响。本研究将为阐明海参岩藻聚糖硫酸酯干预肥胖提供理论基础。

随着饮食结构和生活方式的改变，肥胖已经成为全球性疾病，严重危害公众健康。近年来，岩藻聚糖硫酸酯在治疗肥胖、糖尿病等代谢疾病领域显示出良好的应用前景，已成为海洋药物研究的热点之一。本课题以菲律宾刺参岩藻聚糖硫酸酯（fuc-Pg）为研究对象，拟通过高脂饮食（HFD）建立小鼠肥胖模型，探究了fuc-Pg对饮食诱导小鼠肥胖的预防功效及其作用机制。通过检测血清和肝脏中的生化指标验证了fuc-Pg对小鼠肥胖的预防作用，通过检测小肠CD36、ERK1/2、FABP-1的蛋白表达发现fuc-Pg影响肥胖小鼠小肠中脂质代谢。此外，fuc-Pg可以通过抑制肝脏和结肠中的JNK/NF-κB磷酸化而缓解高脂膳食引发的慢性炎症。本研究将为阐明海参岩藻聚糖硫酸酯预防肥胖提供理论基础。