The Adipokine Lipocalin 2 Is Regulated by Obesity and Promotes Insulin Resistance

Qing-Wu Yan, Qin Yang, Nimesh Mody, Timothy E. Graham, Chung-Hsin Hsu, Zhao Xu, Nicholas E. Houstis, Barbara B. Kahn, Evan D. Rosen

Research output: Contribution to journalArticle

275 Citations (Scopus)

Abstract

OBJECTIVE: 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. RESEARCH DESIGN AND METHODS: 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. RESULTS: 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. CONCLUSIONS: Lcn2 is an adipokine with potential importance in insulin resistance associated with obesity.
Original languageEnglish
Pages (from-to)2533-2540
Number of pages8
JournalDiabetes
Volume56
Issue number10
Early online date16 Jul 2007
DOIs
Publication statusPublished - Oct 2007

Keywords

  • 3T3 Cells
  • acute-phase proteins
  • adipocytes
  • adipose tissue
  • animals
  • cell differentiation
  • gene expression regulation
  • insulin resistance
  • lipids
  • lipocalins
  • macrophages
  • male
  • mice
  • mice, inbred C57BL
  • mice, inbred strains
  • obesity
  • oncogene proteins
  • polymerase chain reaction
  • recombinant proteins
  • stromal cells
  • transfection

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  • Cite this

    Yan, Q-W., Yang, Q., Mody, N., Graham, T. E., Hsu, C-H., Xu, Z., Houstis, N. E., Kahn, B. B., & Rosen, E. D. (2007). The Adipokine Lipocalin 2 Is Regulated by Obesity and Promotes Insulin Resistance. Diabetes, 56(10), 2533-2540. https://doi.org/10.2337/db07-0007