海参脑苷脂对肥胖小鼠脂代谢和糖代谢的影响

发布时间：2018-08-17 11:39

【摘要】：海参是一种重要的食物和药物资源，富含多种活性成分，研究证实其具有抗真菌、免疫调节、抗病毒、抗肿瘤和降血压等多种生理功能。脑苷脂是海参重要的次生代谢产物，，具有多种生物活性功能，但是迄今为止对其活性的研究多集中于抗肿瘤方面，尚未发现关于其减肥降脂活性的报道。海地瓜（Acaudinamolpadioides）是一种资源丰富的低值海参，在我国分布广泛。本实验便以海地瓜中提取的脑苷脂及其水解产物长链碱基为主体，研究了其对肥胖小鼠的脂代谢和糖代谢的影响，并从分子水平上对其作用机理进行了探讨，为海参脑苷脂的深度开发利用提供科学依据。本实验采用饮食诱导肥胖小鼠为模型，首先对海参脑苷脂及其长链碱基在肥胖小鼠脂代谢和糖代谢方面的生物活性进行了评价。研究发现，海参脑苷脂及其长链碱基能够有效抑制小鼠体脂肪蓄积、显著降低肝脏脂质含量，对饮食诱导肥胖小鼠的脂代谢情况具有明显的改善效果。在糖代谢方面，海参脑苷脂及其长链碱基均对肥胖小鼠口服葡萄糖耐受性有明显的改善，海参脑苷脂组和长链碱基组小鼠空腹血糖含量与胰岛素含量均明显降低，HOMA-IR指数显著降低，表明海参脑苷脂及其长链碱基均可以有效提高胰岛素敏感性，改善胰岛素抵抗现象。为了进一步研究海参脑苷脂对肝脏脂质代谢的影响，本研究从脂肪合成和分解代谢方面对它的作用机理进行了探究。实验结果表明，海参脑苷脂可以明显下调肥胖小鼠肝脏SREBP-1c及其靶基因FAS与ME的表达，并且可以明显抑制肝脏FAS活性以及ME活性，有效抑制肝脏脂肪酸的合成产生，从而抑制肥胖小鼠肝脏TG的蓄积。另一方面，海参脑苷脂还可以明显抑制PPARγ的表达，进而影响肝脏脂质代谢，减少肝脏TG的蓄积。海参脑苷脂通过以上途径发挥其降低肝脏脂质积累的生物活性。最后本实验从脂质摄入、合成、分解以及脂肪细胞分化等方面入手，对海参脑苷脂影响脂肪组织脂质代谢的分子机理进行了探究。研究发现，一方面海参脑苷脂可以明显抑制脂肪组织LPL和VLDLR的表达，从而抑制脂肪组织的脂质摄取，进而抑制脂肪生成达到抑制脂肪组织蓄积的作用。另一方面海参脑苷脂可以明显上调脂肪组织中UCP1、ATGL和HSL基因的表达，促进脂肪动员和甘油三酯的分解利用，以此达到减少脂肪组织蓄积的作用。综上说明，海参脑苷脂通过减少脂肪组织对脂质的摄入，以及升高脂肪组织对脂质的利用两条途径来达到抑制脂肪组织蓄积的作用。本论文首次研究了海参脑苷脂对饮食诱导肥胖小鼠脂代谢和糖代谢的影响，还比较了海参脑苷脂及其长链碱基的生物活性差异，为其构效关系研究提供了参考依据。本文的研究结果对海参脑苷脂在保健食品和药品中的开发利用提供了新的科学依据。
[Abstract]:Sea cucumber is a kind of important food and medicine resource, which is rich in many active components. It has many physiological functions such as antifungal, immune regulation, antivirus, antitumor and lowering blood pressure. Cerebroside is an important secondary metabolite of sea cucumber, which has a variety of bioactive functions. However, so far, most of the studies on its activity have focused on anti-tumor, and no report has been found on its weight loss and lipid-lowering activity. (Acaudinamolpadioides) is a kind of low-valued sea cucumber with abundant resources, which is widely distributed in China. In this experiment, the effects of Cereoside and its hydrolysate, long chain base, on lipid metabolism and glucose metabolism in obese mice were studied, and the mechanism of their action was discussed at the molecular level. To provide scientific basis for the further development and utilization of sea cucumber brain glycosides. In this experiment, diet induced obesity mice were used as the model. Firstly, the biological activities of brain glycosides and their long chain bases of sea cucumber on lipid and glucose metabolism in obese mice were evaluated. It was found that the brain glycosides and their long chain bases of sea cucumber could effectively inhibit the accumulation of body fat and decrease the content of lipids in the liver, which could improve the lipid metabolism of obese mice induced by diet. In the aspect of glucose metabolism, the oral glucose tolerance of obese mice was significantly improved by sea cucumber glucoside and its long chain bases. The fasting blood glucose content and insulin content of mice in brain glycosides group and long chain base group of sea cucumber were significantly decreased. The HOMA-IR index was significantly decreased, which indicated that both brain glycosides and their long chain bases could increase insulin sensitivity and improve insulin resistance. In order to study the effect of brain glycosides of sea cucumber on lipid metabolism of liver, the mechanism of lipid synthesis and catabolism was studied. The results showed that sea cucumber glucosides could significantly down-regulate the expression of SREBP-1c and its target genes FAS and ME in the liver of obese mice, inhibit the activity of FAS and ME in the liver, and inhibit the synthesis of fatty acids in the liver. Thus, the accumulation of TG in liver of obese mice was inhibited. On the other hand, the brain glycosides of sea cucumber can significantly inhibit the expression of PPAR 纬, thereby affect the lipid metabolism of the liver and reduce the accumulation of TG in the liver. Sea cucumber brain glycosides play a role in reducing liver lipid accumulation through these pathways. Finally, the molecular mechanism of brain glycosides affecting lipid metabolism in adipose tissue was investigated from the aspects of lipid intake, synthesis, decomposition and adipocyte differentiation. It was found that, on the one hand, the brain glycosides of sea cucumber could inhibit the expression of LPL and VLDLR in adipose tissue, thus inhibit the lipid uptake of adipose tissue, and then inhibit fat formation and inhibit the accumulation of adipose tissue. On the other hand, the brain glycosides of sea cucumber can obviously upregulate the expression of ATGL and HSL gene in adipose tissue, promote fat mobilization and triglyceride decomposition and utilization, so as to reduce the accumulation of adipose tissue. It is concluded that the brain glycosides of sea cucumber can inhibit the accumulation of adipose tissue by reducing the intake of lipid in adipose tissue and increasing the utilization of lipid in adipose tissue. In this paper, the effects of brain glycosides of sea cucumber on lipid metabolism and glucose metabolism of obese mice induced by diet were studied for the first time, and the differences of biological activities of brain glycosides and their long chain bases were also compared, which provided a reference for the study of structure-activity relationship of brain glycosides of sea cucumbers. The results of this paper provide a new scientific basis for the development and utilization of sea cucumber brain glycosides in health food and medicine.
【学位授予单位】：中国海洋大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R151

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