Sommer Grit, Weise Sebastian, Kralisch Susan, Lossner Ulrike, Bluher Matthias, Stumvoll Michael, Fasshauer Mathias
Department of Internal Medicine III, University of Leipzig, 04103 Leipzig, Germany.
J Cell Biochem. 2009 Jan 1;106(1):103-8. doi: 10.1002/jcb.21980.
Lipocalin-2 (Lcn2) has recently been isolated as an adipocyte-secreted acute phase reactant that plays a role in insulin resistance, obesity, and atherosclerotic disease. In the current study, we determined regulation of Lcn2 by the proinflammatory and insulin resistance-inducing cytokine interleukin (IL)-1beta in 3T3-L1 and brown adipocytes by relative real-time reverse transcription-polymerase chain reaction. Interestingly, IL-1beta dramatically induced Lcn2 mRNA in both adipocyte models. Furthermore, Lcn2 protein secretion was dramatically upregulated in 3T3-L1 adipocytes after 24 h of IL-1beta treatment. Experiments using pharmacological inhibitors indicated that IL-1beta-induced Lcn2 expression is mediated via nuclear factor kappaB and janus kinase 2. Taken together, our results show an upregulation of Lcn2 by IL-1beta in fat cells implicating a potential role of this adipocyte-secreted acute phase reactant in the development of insulin resistance, obesity, and associated disorders including cardiovascular disease.
脂质运载蛋白-2(Lcn2)最近被分离出来,是一种由脂肪细胞分泌的急性期反应物,在胰岛素抵抗、肥胖和动脉粥样硬化疾病中发挥作用。在本研究中,我们通过相对实时逆转录-聚合酶链反应,确定了促炎和诱导胰岛素抵抗的细胞因子白细胞介素(IL)-1β对3T3-L1细胞和棕色脂肪细胞中Lcn2的调控。有趣的是,在两种脂肪细胞模型中,IL-1β均显著诱导Lcn2 mRNA表达。此外,在IL-1β处理24小时后,3T3-L1脂肪细胞中Lcn2蛋白分泌显著上调。使用药理学抑制剂的实验表明,IL-1β诱导的Lcn2表达是通过核因子κB和janus激酶2介导的。综上所述,我们的结果表明,IL-1β可上调脂肪细胞中Lcn2的表达,这意味着这种由脂肪细胞分泌的急性期反应物在胰岛素抵抗、肥胖及包括心血管疾病在内的相关疾病的发展中可能发挥作用。