Department of Biology, Faculty of Science, Hong Kong Baptist University, Hong Kong.
Horm Metab Res. 2012 Oct;44(11):819-24. doi: 10.1055/s-0032-1321909. Epub 2012 Aug 14.
Ginsenoside-Rb1 (Rb1), one of the bioactive components in ginseng extract, is recently reported to be able to promote adipogenesis and peroxisome proliferator-activated receptor gamma (PPARγ) expression. Meanwhile, microRNA-27b (miR-27b) is also identified to regulate adipogenesis by targeting PPARγ2. In the present study, we attempted to link up the Rb1-promoted adipogenesis with PPARγ binding and miR-27b regulation. First, we demonstrated that GW9662, an antagonist of PPARγ, could block Rb1-induced 3T3-L1 differentiation with little toxicity towards cell proliferation. Then, expression levels for both of miR-27b and its primary transcript, pri-mir-27b, were found to decrease upon Rb1 treatment. Again, GW9662 could attenuate the inhibitory effect of Rb1 on both miR-27 and pri-mir-27b expression. Since Rb1 was demonstrated to have binding activity towards PPARγ, we thus speculate that Rb1 may act though PPARγ to downregulate mir-27b gene transcription and mature miR-27b activity, which in turn promotes PPARγ expression and adipogenesis. Enhancement on adipogenesis of adipose tissues is expected to prevent lipotoxicty in nonadipose tissues. Our data may give a better illustration to explain the antidiabetic effect of Rb1 and provide a hint on treatment of lipid related metabolic diseases in the future.
人参皂苷-Rb1(Rb1)是人参提取物中的一种生物活性成分,最近有报道称它能够促进脂肪生成和过氧化物酶体增殖物激活受体γ(PPARγ)的表达。同时,microRNA-27b(miR-27b)也被确定为通过靶向 PPARγ2 来调节脂肪生成。在本研究中,我们试图将 Rb1 促进的脂肪生成与 PPARγ 结合和 miR-27b 调节联系起来。首先,我们证明了 PPARγ 的拮抗剂 GW9662 可以阻断 Rb1 诱导的 3T3-L1 分化,而对细胞增殖几乎没有毒性。然后,发现 Rb1 处理后 miR-27b 和其初级转录物 pri-mir-27b 的表达水平均降低。同样,GW9662 可以减弱 Rb1 对 miR-27 和 pri-mir-27b 表达的抑制作用。由于 Rb1 被证明与人 PPARγ 具有结合活性,因此我们推测 Rb1 可能通过 PPARγ 下调 mir-27b 基因转录和成熟 miR-27b 活性,从而促进 PPARγ 表达和脂肪生成。增强脂肪组织的脂肪生成有望防止非脂肪组织中的脂毒性。我们的数据可能更好地解释了 Rb1 的抗糖尿病作用,并为未来治疗与脂质相关的代谢性疾病提供了线索。