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来自莫氏囊须海参的岩藻依聚糖通过调节Wnt/β-连环蛋白信号通路和下调固醇调节元件结合蛋白-1c(SREBP-1c)的表达来发挥抗脂肪生成活性。

Fucoidan from the sea cucumber Acaudina molpadioides exhibits anti-adipogenic activity by modulating the Wnt/β-catenin pathway and down-regulating the SREBP-1c expression.

作者信息

Xu Hui, Wang Jingfeng, Chang Yaoguang, Xu Jie, Wang Yuming, Long Tengteng, Xue Changhu

机构信息

College of Food Science and Engineering, Ocean University of China, Qingdao, Shandong Province 266003, China.

出版信息

Food Funct. 2014 Jul 25;5(7):1547-55. doi: 10.1039/c3fo60716j.

Abstract

A novel fucoidan, which consists of a 1 → 3-linked tetrafucose repeating unit that is distinctive in its sulphation pattern, was isolated from the sea cucumber Acaudina molpadioides. In the present study, we examined the anti-adipogenic effect of the fucoidan from Acaudina molpadioides (Am-FUC) in vitro and in vivo. Results showed that Am-FUC exhibited an inhibitory effect on the proliferation and differentiation of 3T3-L1 cells. Am-FUC suppressed the differentiation of 3T3-L1 cells, decreasing the content of intracellular triglyceride by 34.07% at the concentration of 200 μg ml(-1). In vivo experiments showed that the subcutaneous, perirenal and epididymal fat content of Am-FUC-treated mice were significantly reduced compared to the HFFD-fed mice. A reverse transcriptase-polymerase chain reaction assay revealed that Am-FUC significantly increased the mRNA expressions of Wnt/β-catenin pathway related factors, namely, Wnt10b, β-catenin, Fz and LRP5, and decreased that of the key transcriptional factors, such as SREBP-1c, PPARγ and C/EBPα. β-Catenin acts as an anti-adipogenic factor to inhibit the expression of PPARγ and C/EBPα, while SREBP-1c can promote the adipocyte differentiation by enhancing the activity of PPARγ. Western blotting results showed that Am-FUC significantly increased the protein level of the total β-catenin and nuclear β-catenin and suppressed that of the SREBP-1c. Am-FUC also significantly inhibited the mRNA expressions of the lipid synthesis related genes such as FAS and GPAT, while had no effect on that of the lipolysis related genes such as HSL and ATGL. These findings suggest that Am-FUC possesses marked anti-adipogenic activity by modulating the Wnt/β-catenin pathway and down-regulating the expression of SREBP-1c.

摘要

从糙海参中分离出一种新型岩藻聚糖,其由1→3连接的四岩藻糖重复单元组成,该单元的硫酸化模式独特。在本研究中,我们在体外和体内检测了糙海参岩藻聚糖(Am-FUC)的抗脂肪生成作用。结果表明,Am-FUC对3T3-L1细胞的增殖和分化具有抑制作用。Am-FUC抑制3T3-L1细胞的分化,在浓度为200μg ml(-1)时,细胞内甘油三酯含量降低了34.07%。体内实验表明,与高脂高糖饮食喂养的小鼠相比,经Am-FUC处理的小鼠皮下、肾周和附睾脂肪含量显著降低。逆转录聚合酶链反应分析显示,Am-FUC显著增加了Wnt/β-连环蛋白通路相关因子Wnt10b、β-连环蛋白、Fz和LRP5的mRNA表达,并降低了关键转录因子如SREBP-1c、PPARγ和C/EBPα的表达。β-连环蛋白作为一种抗脂肪生成因子,可抑制PPARγ和C/EBPα的表达,而SREBP-1c可通过增强PPARγ的活性促进脂肪细胞分化。蛋白质免疫印迹结果显示,Am-FUC显著增加了总β-连环蛋白和核β-连环蛋白的蛋白水平,并抑制了SREBP-1c的蛋白水平。Am-FUC还显著抑制了脂肪酸合成酶(FAS)和甘油-3-磷酸酰基转移酶(GPAT)等脂质合成相关基因的mRNA表达,而对激素敏感脂肪酶(HSL)和脂肪甘油三酯脂肪酶(ATGL)等脂肪分解相关基因的表达没有影响。这些发现表明,Am-FUC通过调节Wnt/β-连环蛋白通路和下调SREBP-1c的表达具有显著的抗脂肪生成活性。

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