J Bio Chem：白皮杉醇可有效抑制脂肪细胞的形成

在红酒、葡萄以及其它水果中发现的结构类似于白藜芦醇的化合物可以有效阻断脂肪细胞发展的细胞过程，这就为控制肥胖提供了一种可行性的治疗方法。(Credit: © OlgaLIS / Fotolia)

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近日，来自普渡大学的研究者在红酒、葡萄以及其它水果中发现了类似于白藜芦醇结构的化合物，这种化合物可以阻断肥胖细胞的生长发育，这就为我们控制肥胖提供了一种潜在的治疗方法。研究者Kee-Hong Kim等在国际杂志Journal of Biological Chemistry上报道了他们的研究的成果：化合物白皮杉醇可以阻断未成熟的肥胖细胞生长和成熟。

这种白皮杉醇化合物是在红酒、葡萄以及花生中发现的，其结构类似于白藜芦醇，被认为是抵御癌症、心脏疾病以及神经变性疾病的化合物。如今研究表明，白皮杉醇也有可能是战胜肥胖的有力武器，另外，白藜芦醇被人体消化后会转变成白皮杉醇。白皮杉醇可以在脂肪形成乃至成熟的时候改变其基因表达的时间、基因的功能以及胰岛素活性。如果白皮杉醇存在时，你将会看见脂肪的形成完全被延迟或者被抑制，研究者Kim说。

Kim表示，未成熟的脂肪细胞（前细胞）一般可以通过长达10天的周期以各种不同的途径来形成成熟的脂肪细胞。尽管这些前体细胞并没有积累成脂质，但是其完全有潜力变成脂肪细胞，我们考虑，脂肪生成有可能是一个重要的延迟或者抑制脂肪细胞形成的分子靶点。在脂肪形成初期，白皮杉醇会结合到未成熟脂肪细胞的胰岛素受体上，阻断胰岛素的能力来控制细胞周期并且激活基因从而抑制脂肪形成的后期必要阶段。

白皮杉醇是对人类有益的化合物，一般存在于红葡萄的种子、蓝莓、百香果和其它水果中，研究者Kim用肥胖的动物模型以及细胞培养系统来进行相应的实验，最终确定了这种白皮杉醇的功效，他所带领的研究小组后期将会发明出免于白皮杉醇降解的方法，并且将白皮杉醇化合物制成聚合物以用于人体，阻止人体脂肪组织的形成。（生物谷：T.Shen编译）

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doi:10.1074/jbc.M111.259721
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Piceatannol, Natural Polyphenolic Stilbene, Inhibits Adipogenesis via Modulation of Mitotic Clonal Expansion and Insulin Receptor-dependent Insulin Signaling in Early Phase of Differentiation*

Jung Yeon Kwon‡, Sang Gwon Seo§, Yong-Seok Heo¶, Shuhua Yue‖, Ji-Xin Cheng‖,**, Ki Won Lee§ and Kee-Hong Kim‡,1

Piceatannol, a natural stilbene, is an analog and a metabolite of resveratrol. Despite a well documented health benefit of resveratrol in intervention of the development of obesity, the role of piceatannol in the development of adipose tissue and related diseases is unknown. Here, we sought to determine the function of piceatannol in adipogenesis and elucidate the underlying mechanism. We show that piceatannol inhibits adipogenesis of 3T3-L1 preadipocytes in a dose-dependent manner at noncytotoxic concentrations. This anti-adipogenic property of piceatannol was largely limited to the early event of adipogenesis. In the early phase of adipogenesis, piceatannol-treated preadipocytes displayed a delayed cell cycle entry into G2/M phase at 24 h after initiation of adipogenesis. Furthermore, the piceatannol-suppressed mitotic clonal expansion was accompanied by reduced activation of the insulin-signaling pathway. Piceatannol dose-dependently inhibited differentiation mixture-induced phosphorylation of insulin receptor (IR)/insulin receptor substrate-1 (IRS-1)/Akt pathway in the early phase of adipogenesis. Moreover, we showed that piceatannol is an inhibitor of IR kinase activity and phosphatidylinositol 3-kinase (PI3K). Our kinetics study of IR further identified a Km value for ATP of 57.8 μm and a Ki value for piceatannol of 28.9 μm. We also showed that piceatannol directly binds to IR and inhibits IR kinase activity in a mixed noncompetitive manner to ATP, through which piceatannol appears to inhibit adipogenesis. Taken together, our study reveals an anti-adipogenic function of piceatannol and highlights IR and its downstream insulin signaling as novel targets for piceatannol in the early phase of adipogenesis.