Department of Biomaterials Science and Engineering, Yonsei University, Seoul 120-749, Republic of Korea.
Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Republic of Korea.
Biochem Biophys Res Commun. 2014 Mar 7;445(2):433-8. doi: 10.1016/j.bbrc.2014.02.017. Epub 2014 Feb 12.
Kirenol, a natural diterpenoid compound, has been reported to possess anti-oxidant, anti-inflammatory, anti-allergic, and anti-arthritic activities; however, its anti-adipogenic effect remains to be studied. The present study evaluated the effect of kirenol on anti-adipogenesis through the activation of the Wnt/β-catenin signaling pathway. Kirenol prevented intracellular lipid accumulation by down-regulating key adipogenesis transcription factors [peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhancer binding proteins α (C/EBPα), and sterol regulatory element binding protein-1c (SREBP-1c)] and lipid biosynthesis-related enzymes [fatty acid synthase (FAS) and acetyl-CoA carboxylase (ACC)], as well as adipocytokines (adiponectin and leptin). Kirenol effectively activated the Wnt/β-catenin signaling pathway, in which kirenol up-regulated the expression of low density lipoprotein receptor related protein 6 (LRP6), disheveled 2 (DVL2), β-catenin, and cyclin D1 (CCND1), while it inactivated glycogen synthase kinase 3β (GSK3β) by increasing its phosphorylation. Kirenol down-regulated the expression levels of PPARγ and C/EBPα, which were up-regulated by siRNA knockdown of β-catenin. Overall, kirenol is capable of inhibiting the differentiation and lipogenesis of 3T3-L1 adipocytes through the activation of the Wnt/β-catenin signaling pathway, suggesting its potential as natural anti-obesity agent.
贝壳杉烯醇是一种天然二萜化合物，据报道具有抗氧化、抗炎、抗过敏和抗关节炎活性；然而，其抗脂肪生成作用仍有待研究。本研究通过激活 Wnt/β-连环蛋白信号通路来评估贝壳杉烯醇对脂肪生成的抑制作用。贝壳杉烯醇通过下调关键脂肪生成转录因子（过氧化物酶体增殖物激活受体γ（PPARγ）、CCAAT/增强子结合蛋白α（C/EBPα）和固醇调节元件结合蛋白-1c（SREBP-1c））和脂质生物合成相关酶（脂肪酸合酶（FAS）和乙酰辅酶 A 羧化酶（ACC））以及脂肪细胞因子（脂联素和瘦素）来防止细胞内脂质积累。贝壳杉烯醇有效地激活了 Wnt/β-连环蛋白信号通路，其中贝壳杉烯醇上调了低密度脂蛋白受体相关蛋白 6（LRP6）、蓬乱蛋白 2（DVL2）、β-连环蛋白和细胞周期蛋白 D1（CCND1）的表达，同时通过增加其磷酸化使糖原合酶激酶 3β（GSK3β）失活。贝壳杉烯醇下调了 PPARγ 和 C/EBPα 的表达水平，而β-连环蛋白的 siRNA 敲低则上调了它们的表达水平。总的来说，贝壳杉烯醇能够通过激活 Wnt/β-连环蛋白信号通路抑制 3T3-L1 脂肪细胞的分化和脂肪生成，提示其作为天然抗肥胖剂的潜力。
