以半乳凝素-3为靶点的螺旋藻多糖改善肥胖的作用及机制研究

肥胖是一种慢性代谢性疾病，已经成为国际公共卫生问题。半乳凝素-3（Gal-3）与脂肪组织免疫稳态、巨噬细胞引起的炎症反应、脂肪代谢失衡以及胰岛素抵抗密切相关。实验室前期研究证实螺旋藻总糖（SPP）抑制前体脂肪细胞的增殖和分化，进一步研究发现SPP与Gal-3的糖识别结构域具有较强相互作用，推测SPP通过靶向Gal-3发挥改善肥胖的作用。但SPP的活性功能多糖的结构，其靶向Gal-3及下游分子的作用机制仍不明确。本项目拟分级SPP获得活性功能多糖、解析结构，在细胞和动物水平研究活性功能多糖改善肥胖的作用；利用Gal-3过表达和基因沉默技术证明多糖的作用靶点；从脂肪生成、胰岛素抵抗以及巨噬细胞引起的炎症反应解析多糖改善肥胖的作用机制。项目以鄂尔多斯钝顶螺旋藻为研究材料，首次以Gal-3作为靶点，从三个方面出发，系统研究螺旋藻多糖改善肥胖的作用机制。项目的实施将为肥胖的治疗提供新思路。

Obesity is a chronic disease with metabolic disorder, which has become a worldwide public health problem. Galectin-3 (Gal-3) is associated with immune homeostasis, macrophage-induced inflammation, imbalance of lipid metabolism and insulin resistance. In our previous work, total polysaccharides of Spirulina platensis （SPP）was isolated, which interacted strongly with the carbohydrate recognition domain of Gal-3. Moreover, SPP inhibited the proliferation and differentiation of 3T3L1 preadipocytes. Thus, Gal-3 is speculated as the target for Spirulina polysaccharide to ameliorate obesity. However, the functional components and the mechanisms are still unknown. In this project, SPP will be further fractionated and purified, and the structure of each fraction will be analyzed in detail. The fractions that strongly bind to Gal-3 will be selected, and their effects on ameliorating obesity will be discussed at cellular and animal levels, respectively. The role of Gal-3 will be revealed by over-expression and knockdown of Gal-3. Furthermore, the mechanism of ameliorating obesity by polysaccharide will be analyzed from the perspective of adipogenesis, insulin resistance and macrophage-induced inflammation. Spirulina platensis in Ordos is used as material, and for the first time, Gal-3 is considered as the target of Spirulina. The mechanism on amelioration of obesity will be systemically studied in this project. The results will provide new insights for the treatment of obesity.