Norlichexanthone Isolated from Fungus P16 Promotes the Secretion and Expression of Adiponectin in Cultured ST-13 Adipocytes
Norlichexanthone Isolated from Fungus P16 Promotes the Secretion and Expression of Adiponectin in Cultured ST-13 Adipocytes
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DOI：
10.2174/157340611796150950
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发表时间：
2011-07-01
影响因子：
2.3
通讯作者：
Oikawa, Tsutomu
中科院分区：
文献类型：
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作者：
Ikeda, Megumi;Kurotobi, Yoshiko;Oikawa, Tsutomu
脂联素是一种脂肪来源的蛋白质，具有胰岛素增敏、抗糖尿病和抗动脉粥样硬化活性，这意味着该蛋白质是改善 2 型糖尿病等生活方式相关疾病的潜在靶点。基于我们的假设，即引起脂肪细胞分化的物质也可以充当脂联素分泌增强剂，我们筛选了 96 种真菌培养物提取物的丁醇提取物，以确定其在 ST-13 前脂肪细胞中的分化诱导活性。我们发现真菌P16培养物提取物的丁醇提取物具有这样的活性，并通过活性引导分馏分离出正六己酮作为活性化合物。油红O染色显示正六己酮诱导ST-13细胞的脂肪形成。其分化诱导活性得到了以下观察结果的支持：正六己酮剂量依赖性地增加了脂肪酸结合蛋白和过氧化物酶体增殖物激活受体γ（PPARγ）（脂肪细胞分化标志物）的mRNA表达。蛋白质印迹分析表明，该化合物以剂量依赖性方式增强脂联素蛋白的分泌。在正六己酮处理的 ST-13 细胞中还观察到脂联素 mRNA 表达增加。 Actinomycin D 处理可阻断正六己酮对脂联素 mRNA 表达的增强，表明这是转录增加的结果。荧光素酶报告基因测定表明，正六己酮不太可能是 PPAR γ 的激动剂，这意味着其作用机制可能与噻唑烷二酮类不同，噻唑烷二酮类通过激活 PPAR γ 上调脂联素表达。这些发现表明正六己酮有可能治疗和/或预防与生活方式相关的疾病，包括代谢综合征、2 型糖尿病、动脉粥样硬化和心血管疾病。[图表]。
Adiponectin, an adipose-derived protein, shows insulin-sensitizing, anti-diabetic and anti-atherogenic activities, which implies that the protein represents a potential target to improve lifestyle-related diseases like type 2 diabetes. Based on our hypothesis that agents that cause adipocyte differentiation could also act as adiponectin secretion enhancers, we screened butanol extracts of 96 fungus culture extracts for their differentiation-inducing activity in ST-13 preadipocytes. We found that the butanol extract of a fungus P16 culture extract possessed such an activity, and isolated norlichexanthone as an active compound through activity-guided fractionation. Oil red O staining showed that norlichexanthone induced adipogenesis in ST-13 cells. Its differentiation-inducing activity was supported by the observation that norlichexanthone dose-dependently increased the mRNA expression of fatty acid-binding protein and peroxisome proliferator activated receptor gamma (PPAR gamma), markers of adipocyte differentiation. Western blot analysis demonstrated that the compound enhanced the secretion of adiponectin protein in a dose-dependent manner. An increase in mRNA expression of adiponectin was also observed in the norlichexanthone-treated ST-13 cells. Actinomycin D treatment blocked the enhancement of adiponectin mRNA expression by norlichexanthone, suggesting that it is the result of increased transcription. A luciferase reporter assay indicated that norlichexanthone was unlikely to be an agonist of PPAR gamma, implying that its action of mechanism might differ from those of thiazolidinediones which upregulate adiponectin expression via activation of PPAR gamma. These findings suggest the possibility that norlichexanthone has the potential to treat and/or prevent lifestyle-related diseases, including metabolic syndrome, type 2 diabetes, atherosclerosis and cardiovascular diseases.[GRAPHICS].