Lipocalin-2 is an inflammatory marker closely associated with obesity, insulin resistance, and hyperglycemia in humans.
BACKGROUND
Lipocalin-2, a 25-kDa secreted glycoprotein, is a useful biomarker for early detection of various renal injuries. Because lipocalin-2 is abundantly expressed in adipose tissue and liver, we investigated its relevance to obesity-related pathologies.


METHODS
We used real-time PCR and in-house immunoassays to quantify the mRNA and serum concentrations of lipocalin-2 in C57BL/KsJ db/db obese mice and their age- and sex-matched lean littermates. We analyzed the association between serum lipocalin-2 concentrations and various metabolic and inflammatory variables in 229 persons (121 men and 108 women) recruited from a previous cross-sectional study, and we evaluated the effect of the insulin-sensitizing drug rosiglitazone on serum lipocalin-2 concentrations in 32 diabetic patients (21 men and 11 women).


RESULTS
Compared with the lean littermates, lipocalin-2 mRNA expression in adipose tissue and liver and its circulating concentrations were significantly increased in db/db diabetic/obese mice (P <0.001). These changes were normalized after rosiglitazone treatment. In humans, circulating lipocalin-2 concentrations were positively correlated (P <0.005) with adiposity, hypertriglyceridemia, hyperglycemia, and the insulin resistance index, but negatively correlated (P = 0.002) with HDL cholesterol. There was also a strong positive association between lipocalin-2 concentrations and high sensitivity C-reactive protein (hs-CRP), independent of age, sex, and adiposity (P = 0.007). Furthermore, rosiglitazone-mediated decreases in lipocalin-2 concentrations correlated significantly with increases in insulin sensitivity (r = 0.527; P = 0.002) and decreases in hs-CRP concentrations (r = 0.509; P = 0.003).


CONCLUSIONS
Lipocalin-2 is an inflammatory marker closely related to obesity and its metabolic complications. Measurement of serum lipocalin-2 might be useful for evaluating the outcomes of various clinical interventions for obesity-related metabolic and cardiovascular diseases.
Wang
Yu
Y
Genome Research Center and Department of Biochemistry, University of Hong Kong, Hong Kong, China.
Lam
Karen S L
KS
Kraegen
Edward W
EW
Sweeney
Gary
G
Zhang
Jialiang
J
Tso
Annette W K
AW
Chow
Wing-Sun
WS
Wat
Nelson M S
NM
Xu
Jian Yu
JY
Hoo
Ruby L C
RL
Xu
Aimin
A
D000209:Acute-Phase Proteins; D000328:Adult; D000367:Age Factors; D000368:Aged; D000818:Animals; D015415:Biomarkers / Q000097:blood; D015992:Body Mass Index; D002097:C-Reactive Protein / Q000032:analysis; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D006943:Hyperglycemia / Q000175:diagnosis*; D007249:Inflammation / Q000378:metabolism; D007333:Insulin Resistance; D000071068:Lipocalin-2; D054834:Lipocalins; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D008875:Middle Aged; D009765:Obesity / Q000097:blood / Q000175:diagnosis*; D015513:Oncogene Proteins / Q000097:blood*; D047495:PPAR gamma / Q000819:agonists; D016133:Polymerase Chain Reaction; D011518:Proto-Oncogene Proteins / Q000097:blood*; D000077154:Rosiglitazone; D012737:Sex Factors; D045162:Thiazolidinediones / Q000494:pharmacology / Q000627:therapeutic use
D000209:Acute-Phase Proteins; D015415:Biomarkers; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D015513:Oncogene Proteins; D047495:PPAR gamma; D011518:Proto-Oncogene Proteins; D045162:Thiazolidinediones; D000077154:Rosiglitazone; C071332:Lcn2 protein, mouse; D002097:C-Reactive Protein