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.
2008 Wiley-Liss, Inc.