Carstensen Maren, Wiza Claudia, Röhrig Karin, Fahlbusch Pia, Roden Michael, Herder Christian, Ouwens D Margriet
Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany ; German Center for Diabetes Research (DZD), Düsseldorf, Germany.
German Center for Diabetes Research (DZD), Düsseldorf, Germany ; Institute for Clinical Biochemistry and Pathobiochemistry, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
PLoS One. 2014 Jan 21;9(1):e85906. doi: 10.1371/journal.pone.0085906. eCollection 2014.
Secreted frizzled-related protein 5 (Sfrp5) is an adipokine with anti-inflammatory and insulin-sensitizing properties in mice. However, the mechanism of Sfrp5 action, especially in humans, is largely unknown. Therefore, cytokine release and insulin signaling were analyzed to investigate the impact of Sfrp5 on inflammation and insulin signaling in primary human adipocytes and skeletal muscle cells (hSkMC). Sfrp5 neither affected interleukin (IL)-6, monocyte chemoattractant protein-1 (MCP-1) and adiponectin release from human adipocytes, nor IL-6 and IL-8 release from hSkMC. In tumor necrosis factor (TNF) α-treated adipocytes, Sfrp5 reduced IL-6 release by 49% (p<0.05), but did not affect MCP-1 and adiponectin release. In MCP-1-treated hSkMC, Sfrp5 did not affect cytokine secretion. In untreated adipocytes, Sfrp5 decreased the insulin-mediated phosphorylation of Akt-Ser473, Akt-Thr308, GSK3α-Ser21 and PRAS40-Thr246 by 34% (p<0.01), 31% (p<0.05), 37% (p<0.05) and 34% (p<0.01), respectively, and the stimulation of glucose uptake by 25% (p<0.05). Incubation with TNFα increased the phosphorylation of JNK and NFκB, and impaired insulin signaling. When Sfrp5 and TNFα were combined, there was no additional effect on insulin signaling and JNK phosphorylation, but phosphorylation of NFκB was reversed to basal levels. Sfrp5 had no effect on insulin signaling in untreated or in MCP-1 treated hSkMC. Thus, Sfrp5 lowered IL-6 release and NFκB phosphorylation in cytokine-treated human adipocytes, but not under normal conditions, and decreased insulin signaling in untreated human adipocytes. Sfrp5 did not act on hSkMC. Therefore, the cellular actions of Sfrp5 seem to depend on the type of tissue as well as its inflammatory and metabolic state.
分泌型卷曲相关蛋白5（Sfrp5）是一种在小鼠中具有抗炎和胰岛素增敏特性的脂肪因子。然而，Sfrp5的作用机制，尤其是在人类中的作用机制，在很大程度上尚不清楚。因此，分析了细胞因子释放和胰岛素信号传导，以研究Sfrp5对原代人脂肪细胞和骨骼肌细胞（hSkMC）中炎症和胰岛素信号传导的影响。Sfrp5既不影响人脂肪细胞中白细胞介素（IL）-6、单核细胞趋化蛋白-1（MCP-1）和脂联素的释放，也不影响hSkMC中IL-6和IL-8的释放。在肿瘤坏死因子（TNF）α处理的脂肪细胞中，Sfrp5使IL-6释放减少49%（p<0.05），但不影响MCP-1和脂联素的释放。在MCP-1处理的hSkMC中，Sfrp5不影响细胞因子分泌。在未处理的脂肪细胞中，Sfrp5使胰岛素介导的Akt-Ser473、Akt-Thr308、GSK3α-Ser21和PRAS40-Thr246的磷酸化分别降低34%（p<0.01）、31%（p<0.05）、37%（p<0.05）和34%（p<0.01），并使葡萄糖摄取刺激降低25%（p<0.05）。与TNFα孵育可增加JNK和NFκB的磷酸化，并损害胰岛素信号传导。当Sfrp5与TNFα联合使用时，对胰岛素信号传导和JNK磷酸化没有额外影响，但NFκB的磷酸化恢复到基础水平。Sfrp5对未处理或MCP-1处理的hSkMC中的胰岛素信号传导没有影响。因此，Sfrp5降低了细胞因子处理的人脂肪细胞中IL-6的释放和NFκB的磷酸化，但在正常条件下没有降低，并且降低了未处理的人脂肪细胞中的胰岛素信号传导。Sfrp5对hSkMC没有作用。因此，Sfrp5的细胞作用似乎取决于组织类型及其炎症和代谢状态。
