Embelin attenuates adipogenesis and lipogenesis through activating canonical Wnt signaling and inhibits high-fat diet-induced obesity
Embelin attenuates adipogenesis and lipogenesis through activating canonical Wnt signaling and inhibits high-fat diet-induced obesity
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Embelin 通过激活经典 Wnt 信号传导减弱脂肪生成，并抑制高脂肪饮食引起的肥胖
DOI：
10.1038/ijo.2017.35
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发表时间：
2017-05-01
影响因子：
4.9
通讯作者：
Wang, B.
中科院分区：
文献类型：
--
作者：
Gao, Y.;Li, J.;Wang, B.
背景：最近的研究表明，Embelin，一种天然植物提取物，可能具有预防大鼠体重增加的潜力。方法：采用小鼠ST 2基质细胞和C3 H10 T1/2间充质细胞，研究Embelin对脂肪细胞分化和脂肪生成的影响。探讨了Embelin调节脂肪形成分化和脂肪生成的机制。结果：Embelin可抑制ST 2和C3 H10 T1/2细胞增殖，并向成熟脂肪细胞分化，沿着脂肪形成因子过氧化物酶体增殖物激活受体γ、CCAAT/增强子结合蛋白-α、脂肪细胞蛋白2和脂蛋白酶的抑制作用。Embelin治疗还降低了脂肪生成因子固醇调节元件结合蛋白1、脂肪酸合成酶、乙酰辅酶A羧化酶1和硬脂酰辅酶A去饱和酶1的表达水平。Embelin可促进C3 H10 T1/2细胞β-catenin从胞质向胞核转位。Embelin治疗后β-catenin和TCF-4的核蛋白水平增加。此外，Dickkopf-1（Dkk 1）的表达被Embelin下调，并且在C3 H10 T1/2中过表达Dkk 1逆转了Embelin对脂肪生成和脂肪生成的抑制。体内研究表明，Embelin治疗减少了体重和脂肪的增加，降低了甘油三酯，游离脂肪酸和总胆固醇的血清水平，并改善了HFD喂养小鼠的葡萄糖耐量和胰岛素抵抗。结论：Embelin在体外可有效抑制脂肪形成和脂肪生成，其机制可能与经典Wnt信号通路有关。Embelin有可能防止体重增加和脂肪积累，并改善肥胖相关的葡萄糖耐量受损和胰岛素抵抗的HFD喂养的小鼠。
Background:Recent studies suggest that Embelin, a natural plant extract might have the potential to prevent body weight gain in rats. However, the mechanisms involved remain to be elucidated.Methods:Effects of Embelin on adipocyte differentiation and lipogenesis were studied in murine ST2 stromal cells and C3H10T1/2 mesenchymal cells. The mechanisms through which Embelin regulates adipogenic differentiation and lipogenesis were explored. The in vivo anti-obesity effects of Embelin in high-fat diet (HFD)-induced obesity mice and possible transcriptional impact were investigated.Results:Embelin treatment suppressed ST2 and C3H10T1/2 cells to proliferate, and differentiate into mature adipocytes, along with the inhibition of adipogenic factors peroxisome proliferator-activated receptor γ, CCAAT/enhancer binding protein-α, adipocyte protein 2 and adipsin. Embelin treatment also decreased the expression levels of lipogenic factors sterol regulatory element-binding protein 1, fatty acid synthase, acetyl-CoA carboxylase 1 and stearoyl-Coenzyme A desaturase 1. Embelin promoted the translocation of β-catenin from the cytoplasm into the nucleus in C3H10T1/2. The nuclear protein levels of β-catenin and TCF-4 were increased following Embelin treatment. Furthermore, Dickkopf-1 (Dkk1) expression was downregulated by Embelin, and overexpression of Dkk1 in C3H10T1/2 reversed the inhibition of adipogenesis and lipogenesis by Embelin. In vivo studies showed that Embelin treatment reduced the gain of body weight and fat, decreased the serum level of triglycerides, free fatty acid and total cholesterol, and improved glucose tolerance and insulin resistance in HFD-fed mice. Moreover, Embelin blocked induction of adipogenic and lipogenic factors and Dkk1 in adipose tissue in HFD-fed mice.Conclusions:The present work provides evidences that Embelin is effective in inhibiting adipogenesis and lipogenesis in vitro and the mechanisms may involve canonical Wnt signaling. Embelin has the potential to prevent body weight gain and fat accumulation, and to improve obesity-related glucose tolerance impairment and insulin resistance in the HFD-fed mice.