Blockade of adipocyte differentiation by cordycepin
Blockade of adipocyte differentiation by cordycepin
复制标题
DOI：
10.1111/j.1476-5381.2012.02005.x
复制
发表时间：
2012-10-01
影响因子：
7.3
通讯作者：
Kitamura, Masanori
中科院分区：
文献类型：
--
作者：
Takahashi, Shuhei;Tamai, Minori;Kitamura, Masanori
背景与目的蛹虫草具有抑制前脂肪细胞分化的潜力。然而，提取物中的活性实体及其作用的潜在机制尚不清楚。因此，我们研究了蛹虫草素（3′-脱氧腺苷）是否以及如何抑制脂肪生成。实验方法分别用胰岛素、地塞米松和IBMX诱导原代培养的3T3-L1前脂肪细胞和前脂肪细胞分化，并将其作为体外脂肪形成模型。研究了冬虫夏草素对脂肪形成的影响，特别关注了CCAAT/增强子结合蛋白β (C/EBP β)和PPAR β的调节。冬虫夏草素抑制脂肪前细胞分化过程中脂质积累和脂肪生成标记物的诱导，并阻断脂肪前细胞标记物的下调。这种抗脂肪生成作用是可逆的，由腺苷转运体介导，而不是A1、A2或A3腺苷受体。虫草素的这种作用不能被其他腺苷相关物质复制，包括ATP、ADP和腺苷。早期诱导成脂性C/EBP β - PPAR？途径被虫草素抑制。通过抑制PKB （Akt）和激活AMP激酶来阻断mTORC1被认为是虫草素靶向的关键上游事件。除了对脂肪形成的负面影响外，冬虫夏草素还抑制成熟脂肪细胞中的脂质积累。结论和意义这些结果表明，虫草素的抗脂肪作用是通过干预mTORC1-C/EBP β - PPAR？途径。冬虫夏草素，通过阻断脂肪生成和脂质积累，可能有潜力作为一种治疗药物，有效治疗肥胖和肥胖相关疾病。
BACKGROUND AND PURPOSE Cordyceps militaris has the potential to suppress differentiation of pre-adipocytes. However, the active entities in the extract and the underlying mechanisms of its action are not known. Hence, we investigated whether and how cordycepin (3'-deoxyadenosine), a constituent of C. militaris, inhibits adipogenesis. EXPERIMENTAL APPROACH Differentiation of 3T3-L1 pre-adipocytes and pre-adipocytes in primary cultures was induced by Insulin, dexamethasone and IBMX, and these were used as in vitro models of adipogenesis. The effects of cordycepin on adipogenesis were examined with particular focus on the regulation of CCAAT/enhancer-binding protein beta (C/EBP beta) and PPAR?. KEY RESULTS Cordycepin suppressed the lipid accumulation and induction of adipogenic markers that occurred on differentiation of pre-adipocytes and also blocked the down-regulation of a pre-adipocyte marker. This anti-adipogenic effect was reversible and mediated by an adenosine transporter, but not A1, A2 or A3 adenosine receptors. This effect of cordycepin was not reproduced by other adenosine-related substances, including ATP, ADP and adenosine. Early induction of the adipogenic C/EBP beta PPAR? pathway was suppressed by cordycepin. Blockade of mTORC1 via inhibition of PKB (Akt) and activation of AMP kinase was identified as the crucial upstream event targeted by cordycepin. In addition to its negative effect on adipogenesis, cordycepin suppressed lipid accumulation in mature adipocytes. CONCLUSIONS AND IMPLICATIONS These results suggest that the anti-adipogenic effects of cordycepin occur through its intervention in the mTORC1-C/EBP beta PPAR? pathway. Cordycepin, by blocking both adipogenesis and lipid accumulation, may have potential as a therapeutic agent for effective treatment of obesity and obesity-related disorders.