Inhibitory Effect of Piceatannol on TNF-α-Mediated Inflammation and Insulin Resistance in 3T3-L1 Adipocytes
Inhibitory Effect of Piceatannol on TNF-α-Mediated Inflammation and Insulin Resistance in 3T3-L1 Adipocytes
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DOI：
10.1021/acs.jafc.7b01567
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发表时间：
2017-06-14
影响因子：
6.1
通讯作者：
Yu, Liangli Lucy
中科院分区：
文献类型：
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作者：
Li, Yanfang;Yang, Puyu;Yu, Liangli Lucy
picetanol是葡萄和蓝莓中的一种生物活性成分，通过共培养脂肪细胞和巨噬细胞系统研究了其降低脂肪细胞炎症活性的潜力，并通过3T3-L1脂肪细胞模型研究了其抑制肿瘤坏死因子- α (tnf - α)介导的炎症和相关胰岛素抵抗的潜力。10 μ M皮杉醇可显著降低共培养系统中炎症因子tnf - α和单核细胞趋化蛋白-1 （MCP-1）的释放，分别减少19%和31%。皮杉醇预处理还能抑制tnf α诱导的3T3-L1脂肪细胞中白细胞介素-6 （IL-6）和MCP-1 mRNA和蛋白水平的表达。皮杉醇还部分改善了胰岛素刺激的葡萄糖摄取功能障碍，这是由3T3-L1脂肪细胞中的tnf - α减少的。此外，这种抑制作用是通过抑制NF-kappa B p65的核易位和c-Jun n -末端激酶(JNK)-丝裂原活化蛋白激酶（MAPK）的激活，显著阻断I κ B α磷酸化和核因子κ B （NF-kappa B）的活化而介导的。此外，Akt依赖性叉头盒O1 （FoxO1）信号通路通过抑制Akt和FoxO1磷酸化表达的下调，参与胰岛素刺激下葡萄糖摄取的恢复。这些结果表明，皮杉醇具有改善肥胖脂肪组织慢性炎症和胰岛素敏感性的潜力。
Piceatannol, a bioactive component in grape and blueberry, was examined for its potential in decreasing the inflammatory activities in adipocytes using a cocultured adipocyte and macrophage system, and suppressing tumor necrosis factor-alpha (TNF-alpha)-mediated inflammation and the related insulin resistance using a 3T3-L1 adipocyte model. Piceatannol at 10 mu M significantly reduced the release of inflammatory cytokines of TNF-alpha and monocyte chemoattractant protein-1 (MCP-1) by 19 and 31% in the cocultured system, respectively. Pretreatment with piceatannol also inhibited TNF-alpha-induced expression of interleukin-6 (IL-6) and MCP-1 at both mRNA and protein levels in the 3T3-L1 adipocytes. Piceatannol also partially improved the malfunction of insulin-stimulated glucose uptake, which was reduced by TNF-alpha in 3T3-L1 adipocytes. Furthermore, the inhibitions were mediated by significant blocking of I kappa B alpha phosphorylation and nuclear factor-kappa B (NF-kappa B) activation through suppressing nuclear translocation of NF-kappa B p65 along with c-Jun N-terminal kinase (JNK)-mitogen activated protein kinase (MAPK) activation. In addition, the Akt-dependent forkhead box O1 (FoxO1) signaling pathway was involved in the restoration of insulin-stimulated glucose uptake through suppressing the down-regulation of phosphorylation of Akt and FoxO1 expressions. These results suggested the potential of piceatannol in improving chronic inflammatory condition and insulin sensitivity in obese adipose tissues.