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Lipocalin-2 Is an Inflammatory Marker Closely Associated with Obesity, Insulin Resistance, and Hyperglycemia in Humans
Abstract
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.
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“Most importantly, lipocalin 2 (siderocalin/NGAL) is strongly associated with the development of diabetes [612,613].”
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Cites
1 retracted
Visfatin: A Protein Secreted by Visceral Fat That Mimics the Effects of Insulin
Fukuhara, A., Matsuda, M., Nishizawa, M., Segawa, K., Tanaka, M., Kishimoto, K., Matsuki, Y., Murakami, M., Ichisaka, T., Murakami, H., et al. (2005) · Science · doi:10.1126/science.1097243 · Cited by 1,906
RetractedMatthews, D. R., Hosker, J. P., Rudenski, A. S., Naylor, B. A., Treacher, D. F., & Turner, R. C. (1985) · Diabetologia · doi:10.1007/bf00280883 · Cited by 31,502
Grundy, S. M., Bilheimer, D. W., Chait, A., Clark, L. T., Denke, M. A., Havel, R. J., Hazzard, W. R., Hulley, S. B., Hunninghake, D. B., Kreisberg, R. A., et al. (1993) · JAMA · doi:10.1001/jama.269.23.3015 · Cited by 27,944
Expert Panel on Detection, E. (2001) · JAMA: The Journal of the American Medical Association · doi:10.1001/jama.285.19.2486 · Cited by 26,011
(2004) · The Lancet · doi:10.1016/s0140-6736(03)15268-3 · Cited by 12,717
Obesity is associated with macrophage accumulation in adipose tissue
Weisberg, S. P., McCann, D., Desai, M., Rosenbaum, M., Leibel, R. L., & Ferrante, A. W. (2003) · Journal of Clinical Investigation · doi:10.1172/jci200319246 · Cited by 10,041
Xu, H., Barnes, G. T., Yang, Q., Tan, G., Yang, D., Chou, C. J., Sole, J., Nichols, A., Ross, J. S., Tartaglia, L. A., et al. (2003) · Journal of Clinical Investigation · doi:10.1172/jci200319451 · Cited by 6,760
Inflammation, stress, and diabetes
Wellen, K. E., & Hotamisligil, G. S. (2005) · Journal of Clinical Investigation · doi:10.1172/jci25102 · Cited by 4,143
Adiponectin and Adiponectin Receptors
Kadowaki, T., & Yamauchi, T. (2005) · Endocrine Reviews · doi:10.1210/er.2005-0005 · Cited by 2,634
Adipose tissue, adipokines, and inflammation
Fantuzzi, G. (2005) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2005.02.023 · Cited by 2,606
Mishra, J., Dent, C., Tarabishi, R., Mitsnefes, M. M., Ma, Q., Kelly, C., Ruff, S. M., Zahedi, K., Shao, M., Bean, J., et al. (2005) · The Lancet · doi:10.1016/s0140-6736(05)74811-x · Cited by 2,394
Adipokines: inflammation and the pleiotropic role of white adipose tissue
Trayhurn, P., & Wood, I. S. (2004) · British Journal of Nutrition · doi:10.1079/bjn20041213 · Cited by 2,210
Adipose Tissue, Inflammation, and Cardiovascular Disease
Berg, A. H., & Scherer, P. E. (2005) · Circulation Research · doi:10.1161/01.res.0000163635.62927.34 · Cited by 2,113
Serum retinol binding protein 4 contributes to insulin resistance in obesity and type 2 diabetes
Yang, Q., Graham, T. E., Mody, N., Preitner, F., Peroni, O. D., Zabolotny, J. M., Kotani, K., Quadro, L., & Kahn, B. B. (2005) · Nature · doi:10.1038/nature03711 · Cited by 2,086
Lipocalin 2 mediates an innate immune response to bacterial infection by sequestrating iron
Flo, T. H., Smith, K. D., Sato, S., Rodriguez, D. J., Holmes, M. A., Strong, R. K., Akira, S., & Aderem, A. (2004) · Nature · doi:10.1038/nature03104 · Cited by 1,877
Isolation and primary structure of NGAL, a novel protein associated with human neutrophil gelatinase
Kjeldsen, L., Johnsen, A., Sengeløv, H., & Borregaard, N. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)82217-7 · Cited by 1,286
Cancello, R., Henegar, C., Viguerie, N., Taleb, S., Poitou, C., Rouault, C., Coupaye, M., Pelloux, V., Hugol, D., Bouillot, J.-L., et al. (2005) · Diabetes · doi:10.2337/diabetes.54.8.2277 · Cited by 1,164
Hotamışlıgil, G. S., Johnson, R. S., Distel, R. J., Ellis, R., Papaioannou, V. E., & Spiegelman, B. M. (1996) · Science · doi:10.1126/science.274.5291.1377 · Cited by 915
Therapeutic roles of peroxisome proliferator-activated receptor agonists
Staels, B., & Fruchart, J.-C. (2005) · Diabetes · doi:10.2337/diabetes.54.8.2460 · Cited by 646
Xu, A., Wang, Y., Xu, J. Y., Stejskal, D., Tam, S., Zhang, J., Wat, N. M. S., Wong, W. K., & Lam, K. S. (2006) · Clinical Chemistry · doi:10.1373/clinchem.2005.062463 · Cited by 597
Self-citationThe Metabolic Syndrome: Inflammation, Diabetes Mellitus, and Cardiovascular Disease
Haffner, S. M. (2005) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2005.11.010 · Cited by 568
Mishra, J., Mori, K., Ma, Q., Kelly, C. N., Barasch, J. M., & Devarajan, P. (2004) · American Journal of Nephrology · doi:10.1159/000078452 · Cited by 534
Leptin-specific patterns of gene expression in white adipose tissuePreprint
Soukas, A. A., Cohen, P., Socci, N. D., & Friedman, J. M. (2000) · Genes & Development · doi:10.1101/gad.14.8.963 · Cited by 513
Maeda, K., Cao, H., Kono, K., Görgün, C. Z., Furuhashi, M., Uysal, K. T., Cao, Q., Atsumi, G., Malone, H., Krishnan, B. S., et al. (2005) · Cell Metabolism · doi:10.1016/j.cmet.2004.12.008 · Cited by 485
Devireddy, L. R., Teodoro, J. G., Richard, F. A., & Green, M. R. (2001) · Science · doi:10.1126/science.1061075 · Cited by 380
Wang, Y., Xu, A., Knight, C. G., Xu, L. Y., & Cooper, G. J. S. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m200601200 · Cited by 342
Self-citationTsimikas, S., Willerson, J. T., & Ridker, P. M. (2006) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2005.10.066 · Cited by 332
Xu, A., Lam, M. C., Chan, K. W., Wang, Y., Zhang, J., Hoo, R. L. C., Xu, J. Y., Chen, B., Chow, W.-S., Tso, A. W. K., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0408452102 · Cited by 269
Self-citationHyperglycemia-induced Production of Acute Phase Reactants in Adipose Tissue
Lin, Y., Rajala, M. W., Berger, J. P., Moller, D. E., Barzilai, N., & Scherer, P. E. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m107101200 · Cited by 255
Identification of a New Acute Phase Protein
Liu, Q., & Nilsen‐Hamilton, M. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.38.22565 · Cited by 251
Kratchmarova, I., Kalume, D. E., Blagoev, B., Scherer, P. E., Podtelejnikov, A. V., Molina, H., Bickel, P. E., Andersen, J., Fernandez, M. M., Bunkenborg, J., et al. (2002) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m200006-mcp200 · Cited by 251
Tataranni, P. A., & Ortega, E. (2005) · Diabetes · doi:10.2337/diabetes.54.4.917 · Cited by 241
Boord, J. B., Maeda, K., Makowski, L., Babaev, V. R., Fazio, S., Linton, M. F., & Hotamışlıgil, G. S. (2002) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.0000033090.81345.e6 · Cited by 172
IL-1β-Specific Up-Regulation of Neutrophil Gelatinase-Associated Lipocalin Is Controlled by IκB-ζ
Cowland, J. B., Muta, T., & Borregaard, N. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.176.9.5559 · Cited by 151
SV40-induced expression of mouse gene 24p3 involves a post-transcriptional mechanism.
Hraba-Renevey, S., Türler, H., Kress, M., Salomon, C., & Weil, R. (1989) · PubMed · Cited by 151
Meheus, L., Fransen, L. M., Raymackers, J., Blockx, H., BEEUMEN, J. V., Bun, S. M. V., & VOORDE, A. V. D. (1993) · The Journal of Immunology · doi:10.4049/jimmunol.151.3.1535 · Cited by 131
Surwit, R. S., & Feinglos, M. N. (1984) · Annals of Behavioral Medicine · doi:10.1093/abm/6.1.8 · Cited by 97
PKBα is required for adipose differentiation of mouse embryonic fibroblasts
Baudry, A., Yang, Z., & Hemmings, B. A. (2006) · Journal of Cell Science · doi:10.1242/jcs.02792 · Cited by 95
Tan, K. C. B., Wat, N. M. S., Tam, S., Janus, E. D., Lam, T., & Lam, K. S. L. (2003) · Diabetes Care · doi:10.2337/diacare.26.8.2323 · Cited by 87
Self-citationAdipokines: Therapeutic Targets for Metabolic Syndrome
Kobayashi, K., & Inoguchi, T. (2005) · Current Drug Targets · doi:10.2174/1389450054021972 · Cited by 70
Jayaraman, A., Roberts, K. A., Yoon, J., Yarmush, D. M., Duan, X., Lee, K., & Yarmush, M. L. (2005) · Biotechnology and Bioengineering · doi:10.1002/bit.20535 · Cited by 68
Fujino, R., Tanaka, K., Morimatsu, M., Tamura, K., Kogo, H., & Hara, T. (2005) · Molecular Endocrinology · doi:10.1210/me.2005-0423 · Cited by 62
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Adipokines in inflammation and metabolic disease
Ouchi, N., Parker, J. L., Lugus, J. J., & Walsh, K. (2011) · Nature Reviews Immunology · doi:10.1038/nri2921 · Cited by 4,625
Metabolic Syndrome and Insulin Resistance: Underlying Causes and Modification by Exercise Training
Roberts, C. K., Hevener, A. L., & Barnard, R. J. (2012) · Comprehensive physiology · doi:10.1002/cphy.c110062 · Cited by 966
Chassaing, B., Srinivasan, G., Delgado, M. A., Young, A. N., Gewirtz, A. T., & Vijay–Kumar, M. (2012) · PLoS ONE · doi:10.1371/journal.pone.0044328 · Cited by 584
Kell, D. B. (2009) · BMC Medical Genomics · doi:10.1186/1755-8794-2-2 · Cited by 554
Chakraborty, S., Kaur, S., Guha, S., & Batra, S. K. (2012) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2012.03.008 · Cited by 503
Metadata
- Authors
- Wang, Y., Lam, K. S. L., Kraegen, E. W., Sweeney, G., Zhang, J., Tso, A. W., Chow, W.-S., Wat, N. M., Xu, J. Y., Hoo, R. L., & Xu, A.
- Affiliations
- Genome Research Center and Department of Biochemistry,
- University of Hong Kong (HK)
- Garvan Institute of Medical Research (AU)
- York University (CA)
- Research Center of Heart, Brain, Hormone and Healthy Aging, and
- Corresponding author
- Xu, Aimin
- Venue
- Clinical Chemistry
- Publisher
- Oxford University Press (OUP)
- Published
- 2007-01-01
- Volume
- 53
- Issue
- 1
- Pages
- 34-41
- ISSN
- 0009-9147 (ISSN-L)
- 1530-8561
- OpenAlex
- W2123416046
- Cited by
- 578
- References
- 42
- Citations by year
- 2026: 18 · 2025: 29 · 2024: 31 · 2023: 28 · 2022: 45 · 2021: 36 · 2020: 28 · 2019: 39 · 2018: 31 · 2017: 33 · 2016: 20 · 2015: 31 · 2014: 43 · 2013: 35 · 2012: 34
- FWCI
- 12.45
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- Clinical Chemistry (publishedVersion)
- PubMed (publishedVersion)
- The HKU Scholars Hub (University of Hong Kong) (submittedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
- Keywords
- neutrophil gelatinase-associated lipocalin, obesity, insulin resistance, hyperglycemia, inflammation, C-reactive protein, adipose tissue, liver, rosiglitazone, type 2 diabetes, hypertriglyceridemia, HDL cholesterol, db/db mice, biomarkers
- MeSH terms
- Lipocalin-2, Rosiglitazone, Acute-Phase Proteins, Adult, Age Factors, Aged, Animals, C-Reactive Protein, Diabetes Mellitus, Type 2, Enzyme-Linked Immunosorbent Assay, Female, Humans, Hyperglycemia, Inflammation, Insulin Resistance, Male, Mice, Inbred C57BL, Mice, Obese, Middle Aged, Obesity, Proto-Oncogene Proteins, Sex Factors, Biomarkers, Oncogene Proteins, Body Mass Index, Polymerase Chain Reaction, Thiazolidinediones, PPAR gamma, Mice, Lipocalins
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