Article

The Adipokine Lipocalin 2 Is Regulated By Obesity And Promotes Insulin Resistance

Harvard University, Cambridge, Massachusetts, United States
Diabetes (Impact Factor: 8.1). 11/2007; 56(10):2533-40. DOI: 10.2337/db07-0007
Source: PubMed

ABSTRACT

We identified lipocalin 2 (Lcn2) as a gene induced by dexamethasone and tumor necrosis factor-alpha in cultured adipocytes. The purpose of this study was to determine how expression of Lcn2 is regulated in fat cells and to ascertain whether Lcn2 could be involved in metabolic dysregulation associated with obesity.
We examined Lcn2 expression in murine tissues and in 3T3-L1 adipocytes in the presence and absence of various stimuli. We used quantitative Western blotting to observe Lcn2 serum levels in lean and obese mouse models. To assess effects on insulin action, we used retroviral delivery of short hairpin RNA to reduce Lcn2 levels in 3T3-L1 adipocytes.
Lcn2 is highly expressed by fat cells in vivo and in vitro. Expression of Lcn2 is elevated by agents that promote insulin resistance and is reduced by thiazolidinediones. The expression of Lcn2 is induced during 3T3-L1 adipogenesis in a CCAAT/enhancer-binding protein-dependent manner. Lcn2 serum levels are elevated in multiple rodent models of obesity, and forced reduction of Lcn2 in 3T3-L1 adipocytes improves insulin action. Exogenous Lcn2 promotes insulin resistance in cultured hepatocytes.
Lcn2 is an adipokine with potential importance in insulin resistance associated with obesity.

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    • "Lipocalin-2 is a protein produced by liver, pancreas and adipose tissue in response to inflammation and plays a role in innate immunity by sequestrating iron and subsequently limiting iron availability for pathogenic bacteria [27]. There is evidence that obesity is characterized by increased circulating levels [34] and increased adipocyte expression of lipocalin-2 [35,36]. However, these data have not been confirmed in pediatric obese population [37]. "
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    ABSTRACT: Obesity and iron deficiency (ID) are two of the most common nutritional disorders in the world. In children both conditions deserve particular attention. Several studies revealed an association between obesity and iron deficiency in children and, in some cases, a reduced response to oral supplementation. The connecting mechanism, however, is not completely known. This review is focused on: (1) iron deficiency in obese children and the role of hepcidin in the connection between body fat and poor iron status; (2) iron status and consequences on health, in particular on cognitive function; (3) cognitive function and obesity; (4) suggestion of a possible link between cognitive dysfunction and ID in pediatric obesity; and implications for therapy and future research.
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    • "Also, the increased adipose tissue expression of LCN2 in obesity was correlated to body mass index (Yoo et al., 2014) and to increased activities of both MMP-2 and MMP-9, reinforcing its potential participation in the low-grade chronic inflammation associated with obesity (Catalan et al., 2009). Moreover, LCN2 was also shown to impact in the energy metabolism, even in the absence of increased inflammation, since exogenous recombinant LCN2 is able to increase glucose production in hepatocytes (Yan et al., 2007). The precise function and relevance of LCN2 in obesity and in energy metabolism is, nonetheless, quite controversial since studies with LCN2-null mice were inconclusive. "
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    ABSTRACT: Lipocalin-2 (LCN2) is an acute-phase protein that, by binding to iron-loaded siderophores, acts as a potent bacteriostatic agent in the iron-depletion strategy of the immune system to control pathogens. The recent identification of a mammalian siderophore also suggests a physiological role for LCN2 in iron homeostasis, specifically in iron delivery to cells via a transferrin-independent mechanism. LCN2 participates, as well, in a variety of cellular processes, including cell proliferation, cell differentiation and apoptosis, and has been mostly found up-regulated in various tissues and under inflammatory states, being its expression regulated by several inducers. In the central nervous system less is known about the processes involving LCN2, namely by which cells it is produced/secreted, and its impact on cell proliferation and death, or in neuronal plasticity and behaviour. Importantly, LCN2 recently emerged as a potential clinical biomarker in multiple sclerosis and in aging-related cognitive decline. Still, there are conflicting views on the role of LCN2 in pathophysiological processes, with some studies pointing to its neurodeleterious effects, while others indicate neuroprotection. Herein, these various perspectives are reviewed and a comprehensive and cohesive view of the general function of LCN2, particularly in the brain, is provided. Copyright © 2015. Published by Elsevier Ltd.
    No preview · Article · Jul 2015 · Progress in Neurobiology
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    • "The adipokine lipocalin 2 (LCN2) is a member of the lipocalin family that transports small lipophilic ligands and is highly expressed by fat cells both in vitro and in vivo[26]. Levels of LCN2 mRNA are dramatically increased in the adipose tissue and liver of ob/ob mice, while reducing LCN2 expression leads to a decrease in PPARγ expression [27]. "
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