The adipokine lipocalin 2 is regulated by obesity and promotes insulin resistance.
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.


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.
Yan
Qing-Wu
QW
Division of Endocrinology, Diabetes, and Metabolism, Beth Israel Deaconess Medical Center, Boston, MA 02115, USA.
Yang
Qin
Q
Mody
Nimesh
N
Graham
Timothy E
TE
Hsu
Chung-Hsin
CH
Xu
Zhao
Z
Houstis
Nicholas E
NE
Kahn
Barbara B
BB
Rosen
Evan D
ED
D016475:3T3 Cells; D000209:Acute-Phase Proteins / Q000235:genetics / Q000502:physiology*; D017667:Adipocytes / Q000187:drug effects / Q000502:physiology; D000273:Adipose Tissue / Q000187:drug effects / Q000502:physiology; D000818:Animals; D002454:Cell Differentiation; D005786:Gene Expression Regulation; D007333:Insulin Resistance / Q000502:physiology; D008055:Lipids / Q000235:genetics; D000071068:Lipocalin-2; D054834:Lipocalins; D008264:Macrophages / Q000187:drug effects / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D009765:Obesity / Q000235:genetics / Q000503:physiopathology; D015513:Oncogene Proteins / Q000097:blood / Q000235:genetics / Q000502:physiology*; D016133:Polymerase Chain Reaction; D011994:Recombinant Proteins / Q000494:pharmacology; D017154:Stromal Cells / Q000187:drug effects / Q000502:physiology; D014162:Transfection
D000209:Acute-Phase Proteins; D008055:Lipids; D000071068:Lipocalin-2; D054834:Lipocalins; C086724:Lipofectamine; D015513:Oncogene Proteins; D011994:Recombinant Proteins; C071332:Lcn2 protein, mouse