Toosendanin inhibits adipogenesis by activating Wnt/β-catenin signaling.
Toosendanin inhibits adipogenesis by activating Wnt/β-catenin signaling.
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川楝素通过激活 Wnt/β-catenin 信号传导抑制脂肪生成
DOI：
10.1038/s41598-018-22873-x
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发表时间：
2018-03-15
影响因子：
4.6
通讯作者：
Yin W
中科院分区：
文献类型：
--
作者：
Chen TX;Cheng XY;Wang Y;Yin W
仙丹素（TSN）是一种从仙丹中提取的三萜，具有抗氧化、抗炎、抗过敏和抗关节炎的活性。然而，其抗脂肪生成作用尚不清楚。在这里，我们发现TSN剂量依赖性地减弱了前脂肪细胞3T3-L1的脂质积累，油红O染色证实了这一点。TSN还显著下调脂肪细胞因子（脂联素和瘦素）、CCAAT/增强子结合蛋白α (C/EBP-α)、过氧化物酶体增殖物激活受体γ (PPAR-γ)、脂肪酸合成酶和乙酰辅酶a羧化酶的mRNA和蛋白水平。为了了解其机制，我们观察到TSN有效激活了Wnt/β-catenin通路，其中TSN增加了低密度脂蛋白受体相关蛋白6、disheveled 2、β-catenin和cyclin D1的表达水平，同时通过增强其磷酸化使糖原合酶激酶3β失活。此外，TSN还能降低高脂饲料（HFD）喂养小鼠的性腺白色脂肪重量和血清三酰甘油（TAG）含量。有趣的是，他们的体内研究也表明，TSN促进了β-catenin的表达，但相应地抑制了hfd诱导小鼠中C/EBP-α和PPAR-γ的表达。综上所述，TSN能够通过激活Wnt/β-catenin通路抑制脂肪细胞的脂质生成，提示TSN作为一种天然的抗肥胖药物具有潜在的应用前景。
Toosendanin (TSN), a triterpenoid extracted from Melia toosendan, has been reported to possess anti-oxidant, anti-inflammatory, anti-allergic, and anti-arthritic activities. However, its anti-adipogenic effect remains unknown. Here, we found that TSN dose-dependently attenuated lipid accumulation in preadipocytes 3T3-L1 as evidenced by Oil Red O staining. TSN also significantly downregulated mRNA and protein levels of adipocytokines (adiponectin and leptin), CCAAT/enhancer binding proteins α (C/EBP-α), peroxisome proliferator-activated receptor γ (PPAR-γ), fatty acid synthase, and acetyl-CoA carboxylase in adipocytes. To understand the mechanism, we observed that TSN effectively activated Wnt/β-catenin pathway, in which TSN increased low density lipoprotein receptor related protein 6, disheveled 2, β-catenin, and cyclin D1 expression levels, while it inactivated glycogen synthase kinase 3β by enhancing its phosphorylation. Moreover, TSN reduced weight of gonadal white fat and serum triacylglycerol (TAG) content in high-fat diet (HFD)-fed mice. Interestingly, thein vivostudies also demonstrated that TSN promoted the expression of β-catenin, but accordingly repressed C/EBP-α and PPAR-γ expression in HFD-induced mice. Overall, TSN is capable of inhibiting the lipogenesis of adipocytes by activating the Wnt/β-catenin pathway, suggesting potential application of TSN as a natural anti-obesity agent.
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影响因子：
11.1
作者：
Dan C;Jinjun B;Zi-Chun H;Lin M;Wei C;Xu Z;Ri Z;Shun C;Wen-Zhu S;Qing-Cai J;Wu Y
通讯作者：
Wu Y
影响因子：
4.1
作者：
Murata, T;Yamaguchi, M
通讯作者：
Yamaguchi, M
影响因子：
5.4
作者：
Xie, Fan;Zhang, Mian;Kou, Jun-Ping
通讯作者：
Kou, Jun-Ping
天然产物川楝素逆转非小细胞肺癌对TRAIL的凋亡抗性
影响因子：
4.6
作者：
Li X;You M;Liu YJ;Ma L;Jin PP;Zhou R;Zhang ZX;Hua B;Ji XJ;Cheng XY;Yin F;Chen Y;Yin W
通讯作者：
Yin W
影响因子：
10.9
作者：
Christodoulides, Constantinos;Lagathu, Claire;Sethi, Jaswinder K.;Vidal-Puig, Antonio
通讯作者：
Vidal-Puig, Antonio