Follistatin-like 1: a potential mediator of inflammation in obesity.
Follistatin-like 1: a potential mediator of inflammation in obesity.
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DOI：
10.1155/2013/752519
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发表时间：
2013
影响因子：
4.6
通讯作者：
Peng Y
中科院分区：
文献类型：
--
作者：
Fan N;Sun H;Wang Y;Wang Y;Zhang L;Xia Z;Peng L;Hou Y;Shen W;Liu R;Yin J;Peng Y
肥胖与慢性低度炎症状态有关，这有助于胰岛素抵抗和2型糖尿病。然而，将肥胖与炎症联系起来的分子机制尚未完全了解。卵泡抑素样1（FSTL 1）是一种新型的促炎细胞因子，在脂肪组织中表达，由前脂肪细胞/脂肪细胞分泌。我们的目的是测试FSTL 1是否在肥胖诱导的炎症和胰岛素抵抗中发挥作用。结果表明，在3 T3-L1前体脂肪细胞分化过程中，FSTL 1的表达明显降低，但TNF-α可使其表达恢复。此外，在肥胖ob/ob小鼠的脂肪组织中以及在超重/肥胖受试者的血清中观察到FSTL 1水平的显著增加。机制研究表明，FSTL 1在3 T3-L1脂肪细胞和RAW 264.7巨噬细胞中诱导炎症反应。重组FSTL 1以剂量依赖性方式上调促炎介质包括IL-6、TNF-α和MCP-1的表达，同时激活两种细胞系中的IKKβ-NFκB和JNK信号通路。此外，FSTL 1损害3 T3-L1脂肪细胞中的胰岛素信号传导，如响应于胰岛素刺激的Akt和IRS-1的磷酸化减弱所揭示的。总之，我们的研究结果表明，FSTL 1是肥胖症中炎症和胰岛素抵抗的潜在介导者。
Obesity is associated with a state of chronic low-grade inflammation, which contributes to insulin resistance and type 2 diabetes. However, the molecular mechanisms that link obesity to inflammation are not fully understood. Follistatin-like 1 (FSTL1) is a novel proinflammatory cytokine that is expressed in adipose tissue and secreted by preadipocytes/adipocytes. We aimed to test whether FSTL1 could have a role in obesity-induced inflammation and insulin resistance. It was found that FSTL1 expression was markedly decreased during differentiation of 3T3-L1 preadipocytes but reinduced by TNF-α. Furthermore, a significant increase in FSTL1 levels was observed in adipose tissue of obese ob/ob mice, as well as in serum of overweight/obese subjects. Mechanistic studies revealed that FSTL1 induced inflammatory responses in both 3T3-L1 adipocytes and RAW264.7 macrophages. The expression of proinflammatory mediators including IL-6, TNF-α, and MCP-1 was upregulated by recombinant FSTL1 in a dose-dependent manner, paralleled with activation of the IKKβ-NFκB and JNK signaling pathways in the two cell lines. Moreover, FSTL1 impaired insulin signaling in 3T3-L1 adipocytes, as revealed by attenuated phosphorylation of both Akt and IRS-1 in response to insulin stimulation. Together, our results suggest that FSTL1 is a potential mediator of inflammation and insulin resistance in obesity.
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影响因子：
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