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Published in: Cardiovascular Diabetology 1/2012

Open Access 01-12-2012 | Original investigation

Lipocalin-2, glucose metabolism and chronic low-grade systemic inflammation in Chinese people

Authors: Ying Huang, Zhen Yang, Zi Ye, Qin Li, Jie Wen, Xiaoming Tao, Lili Chen, Min He, Xuanchun Wang, Bin Lu, Zhaoyun Zhang, Weiwei Zhang, Shen Qu, Renming Hu

Published in: Cardiovascular Diabetology | Issue 1/2012

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Abstract

Background

Lipocalin-2 is a novel adipokine with connection to insulin resistance. In this study, we aimed to investigate the association of serum lipocalin-2 with glucose metabolism and other metabolic phenotype in a large-scale Chinese population.

Methods

We evaluated serum lipocalin-2 in a cross-sectional sample of 2519 Chinese aged from 50 to 82 year in a Shanghai downtown district by ELISA. Glucose, insulin, lipid profile, inflammatory markers, and adipokines were also measured.

Results

Serum lipocalin-2 was significantly higher in subjects with isolated impaired fasting glucose, isolated impaired glucose tolerance, combined impaired fasting glucose/impaired glucose tolerance and newly-diagnosed type 2 diabetes than in those with normal glucose regulation. Lipocalin-2 elevation was clearly associated with a higher risk for impaired glucose regulation (OR 1.30 for each 10 ng/ml increase in serum lipocalin-2, 95% CI 1.23-1.62, p = 0.009) after adjustment of age, gender, smoking, alcohol drinking, family history of diabetes, serum CRP, serum adiponectin, serum CXCL5, HOMA-IR, BMI, and waist/hip ratio. The OR for participants with impaired glucose regulation and type 2 diabetes was 1.31 (95% CI 1.21-1.69, p < 0.001).

Conclusions

Our findings suggest that elevated serum lipocalin-2 is closely and independently associated with impaired glucose regulation and type 2 diabetes.
Appendix
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Literature
1.
go back to reference Gelsinger C, Tschoner A, Kaser S, Ebenbichler CF: Adipokine update - new molecules, new functions. Wien Med Wochenschr. 2010, 160 (15-16): 377-390. 10.1007/s10354-010-0781-6.CrossRefPubMed Gelsinger C, Tschoner A, Kaser S, Ebenbichler CF: Adipokine update - new molecules, new functions. Wien Med Wochenschr. 2010, 160 (15-16): 377-390. 10.1007/s10354-010-0781-6.CrossRefPubMed
3.
go back to reference Fernandez-Real JM, Ricart W: Insulin resistance and chronic cardiovascular inflammatory syndrome. Endocr Rev. 2003, 24 (3): 278-301. 10.1210/er.2002-0010.CrossRefPubMed Fernandez-Real JM, Ricart W: Insulin resistance and chronic cardiovascular inflammatory syndrome. Endocr Rev. 2003, 24 (3): 278-301. 10.1210/er.2002-0010.CrossRefPubMed
4.
go back to reference Kjeldsen L, Johnsen AH, Sengelov H, Borregaard N: Isolation and primary structure of NGAL, a novel protein associated with human neutrophil gelatinase. J Biol Chem. 1993, 268 (14): 10425-10432.PubMed Kjeldsen L, Johnsen AH, Sengelov H, Borregaard N: Isolation and primary structure of NGAL, a novel protein associated with human neutrophil gelatinase. J Biol Chem. 1993, 268 (14): 10425-10432.PubMed
5.
go back to reference Kjeldsen L, Bainton DF, Sengelov H, Borregaard N: Identification of neutrophil gelatinase-associated lipocalin as a novel matrix protein of specific granules in human neutrophils. Blood. 1994, 83 (3): 799-807.PubMed Kjeldsen L, Bainton DF, Sengelov H, Borregaard N: Identification of neutrophil gelatinase-associated lipocalin as a novel matrix protein of specific granules in human neutrophils. Blood. 1994, 83 (3): 799-807.PubMed
6.
go back to reference Flower DR: The up-and-down beta-barrel proteins: three of a kind. FASEB J. 1995, 9 (7): 566-567.PubMed Flower DR: The up-and-down beta-barrel proteins: three of a kind. FASEB J. 1995, 9 (7): 566-567.PubMed
7.
go back to reference Devireddy LR, Teodoro JG, Richard FA, Green MR: Induction of apoptosis by a secreted lipocalin that is transcriptionally regulated by IL-3 deprivation. Science. 2001, 293 (5531): 829-834. 10.1126/science.1061075.CrossRefPubMed Devireddy LR, Teodoro JG, Richard FA, Green MR: Induction of apoptosis by a secreted lipocalin that is transcriptionally regulated by IL-3 deprivation. Science. 2001, 293 (5531): 829-834. 10.1126/science.1061075.CrossRefPubMed
8.
go back to reference Stoesz SP, Gould MN: Overexpression of neu-related lipocalin (NRL) in neu-initiated but not ras or chemically initiated rat mammary carcinomas. Oncogene. 1995, 11 (11): 2233-2241.PubMed Stoesz SP, Gould MN: Overexpression of neu-related lipocalin (NRL) in neu-initiated but not ras or chemically initiated rat mammary carcinomas. Oncogene. 1995, 11 (11): 2233-2241.PubMed
9.
go back to reference Flo TH, Smith KD, Sato S, Rodriguez DJ, Holmes MA, Strong RK, Akira S, Aderem A: Lipocalin 2 mediates an innate immune response to bacterial infection by sequestrating iron. Nature. 2004, 432 (7019): 917-921. 10.1038/nature03104.CrossRefPubMed Flo TH, Smith KD, Sato S, Rodriguez DJ, Holmes MA, Strong RK, Akira S, Aderem A: Lipocalin 2 mediates an innate immune response to bacterial infection by sequestrating iron. Nature. 2004, 432 (7019): 917-921. 10.1038/nature03104.CrossRefPubMed
10.
go back to reference Yan QW, Yang Q, Mody N, Graham TE, Hsu CH, Xu Z, Houstis NE, Kahn BB, Rosen ED: The adipokine lipocalin 2 is regulated by obesity and promotes insulin resistance. Diabetes. 2007, 56 (10): 2533-2540. 10.2337/db07-0007.CrossRefPubMed Yan QW, Yang Q, Mody N, Graham TE, Hsu CH, Xu Z, Houstis NE, Kahn BB, Rosen ED: The adipokine lipocalin 2 is regulated by obesity and promotes insulin resistance. Diabetes. 2007, 56 (10): 2533-2540. 10.2337/db07-0007.CrossRefPubMed
11.
go back to reference Wang Y, Lam KS, Kraegen EW, Sweeney G, Zhang J, Tso AW, Chow WS, Wat NM, Xu JY, Hoo RL, et al: Lipocalin-2 is an inflammatory marker closely associated with obesity, insulin resistance, and hyperglycemia in humans. Clin Chem. 2007, 53 (1): 34-41.CrossRefPubMed Wang Y, Lam KS, Kraegen EW, Sweeney G, Zhang J, Tso AW, Chow WS, Wat NM, Xu JY, Hoo RL, et al: Lipocalin-2 is an inflammatory marker closely associated with obesity, insulin resistance, and hyperglycemia in humans. Clin Chem. 2007, 53 (1): 34-41.CrossRefPubMed
12.
go back to reference Law IK, Xu A, Lam KS, Berger T, Mak TW, Vanhoutte PM, Liu JT, Sweeney G, Zhou M, Yang B, et al: Lipocalin-2 deficiency attenuates insulin resistance associated with aging and obesity. Diabetes. 2010, 59 (4): 872-882. 10.2337/db09-1541.PubMedCentralCrossRefPubMed Law IK, Xu A, Lam KS, Berger T, Mak TW, Vanhoutte PM, Liu JT, Sweeney G, Zhou M, Yang B, et al: Lipocalin-2 deficiency attenuates insulin resistance associated with aging and obesity. Diabetes. 2010, 59 (4): 872-882. 10.2337/db09-1541.PubMedCentralCrossRefPubMed
13.
go back to reference Auguet T, Quintero Y, Terra X, Martinez S, Lucas A, Pellitero S, Aguilar C, Hernandez M, Del CD, Richart C: Upregulation of Lipocalin 2 in Adipose Tissues of Severely Obese Women: Positive Relationship With Proinflammatory Cytokines. Obesity (Silver Spring). 2011, 19 (12): 2295-300. 10.1038/oby.2011.61.CrossRef Auguet T, Quintero Y, Terra X, Martinez S, Lucas A, Pellitero S, Aguilar C, Hernandez M, Del CD, Richart C: Upregulation of Lipocalin 2 in Adipose Tissues of Severely Obese Women: Positive Relationship With Proinflammatory Cytokines. Obesity (Silver Spring). 2011, 19 (12): 2295-300. 10.1038/oby.2011.61.CrossRef
14.
go back to reference Yang Z, Zhang Z, Wen J, Wang X, Lu B, Yang Z, Zhang W, Wang M, Feng X, Ling C, et al: Elevated serum chemokine CXC ligand 5 levels are associated with hypercholesterolemia but not a worsening of insulin resistance in Chinese people. J Clin Endocrinol Metab. 2010, 95 (8): 3926-3932. 10.1210/jc.2009-2194.CrossRefPubMed Yang Z, Zhang Z, Wen J, Wang X, Lu B, Yang Z, Zhang W, Wang M, Feng X, Ling C, et al: Elevated serum chemokine CXC ligand 5 levels are associated with hypercholesterolemia but not a worsening of insulin resistance in Chinese people. J Clin Endocrinol Metab. 2010, 95 (8): 3926-3932. 10.1210/jc.2009-2194.CrossRefPubMed
15.
go back to reference Zhou BF: Predictive values of body mass index and waist circumference for risk factors of certain related diseases in Chinese adults-study on optimal cut-off points of body mass index and waist circumference in Chinese adults. Biomed Environ Sci. 2002, 15 (1): 83-96.PubMed Zhou BF: Predictive values of body mass index and waist circumference for risk factors of certain related diseases in Chinese adults-study on optimal cut-off points of body mass index and waist circumference in Chinese adults. Biomed Environ Sci. 2002, 15 (1): 83-96.PubMed
16.
go back to reference American Diabetes Association: Diagnosis and classification of diabetes mellitus. Diabetes Care. 2005, 28: S37-S42.CrossRef American Diabetes Association: Diagnosis and classification of diabetes mellitus. Diabetes Care. 2005, 28: S37-S42.CrossRef
17.
go back to reference Cakal E, Ozkaya M, Engin-Ustun Y, Ustun Y: Serum lipocalin-2 as an insulin resistance marker in patients with polycystic ovary syndrome. J Endocrinol Invest. 2011, 34 (2): 97-100.CrossRefPubMed Cakal E, Ozkaya M, Engin-Ustun Y, Ustun Y: Serum lipocalin-2 as an insulin resistance marker in patients with polycystic ovary syndrome. J Endocrinol Invest. 2011, 34 (2): 97-100.CrossRefPubMed
18.
go back to reference Yang J, Goetz D, Li JY, Wang W, Mori K, Setlik D, Du T, Erdjument-Bromage H, Tempst P, Strong R, et al: An iron delivery pathway mediated by a lipocalin. Mol Cell. 2002, 10 (5): 1045-1056. 10.1016/S1097-2765(02)00710-4.CrossRefPubMed Yang J, Goetz D, Li JY, Wang W, Mori K, Setlik D, Du T, Erdjument-Bromage H, Tempst P, Strong R, et al: An iron delivery pathway mediated by a lipocalin. Mol Cell. 2002, 10 (5): 1045-1056. 10.1016/S1097-2765(02)00710-4.CrossRefPubMed
19.
go back to reference Cooksey RC, Jouihan HA, Ajioka RS, Hazel MW, Jones DL, Kushner JP, McClain DA: Oxidative stress, beta-cell apoptosis, and decreased insulin secretory capacity in mouse models of hemochromatosis. Endocrinology. 2004, 145 (11): 5305-5312. 10.1210/en.2004-0392.CrossRefPubMed Cooksey RC, Jouihan HA, Ajioka RS, Hazel MW, Jones DL, Kushner JP, McClain DA: Oxidative stress, beta-cell apoptosis, and decreased insulin secretory capacity in mouse models of hemochromatosis. Endocrinology. 2004, 145 (11): 5305-5312. 10.1210/en.2004-0392.CrossRefPubMed
20.
go back to reference Borel MJ, Beard JL, Farrell PA: Hepatic glucose production and insulin sensitivity and responsiveness in iron-deficient anemic rats. Am J Physiol. 1993, 264 (3 Pt 1): E380-E390.PubMed Borel MJ, Beard JL, Farrell PA: Hepatic glucose production and insulin sensitivity and responsiveness in iron-deficient anemic rats. Am J Physiol. 1993, 264 (3 Pt 1): E380-E390.PubMed
21.
go back to reference Farrell PA, Beard JL, Druckenmiller M: Increased insulin sensitivity in iron-deficient rats. J Nutr. 1988, 118 (9): 1104-1109.PubMed Farrell PA, Beard JL, Druckenmiller M: Increased insulin sensitivity in iron-deficient rats. J Nutr. 1988, 118 (9): 1104-1109.PubMed
22.
go back to reference Dandona P, Hussain MA, Varghese Z, Politis D, Flynn DM, Hoffbrand AV: Insulin resistance and iron overload. Ann Clin Biochem. 1983, 20 (Pt 2): 77-79.CrossRefPubMed Dandona P, Hussain MA, Varghese Z, Politis D, Flynn DM, Hoffbrand AV: Insulin resistance and iron overload. Ann Clin Biochem. 1983, 20 (Pt 2): 77-79.CrossRefPubMed
23.
go back to reference Sun L, Franco OH, Hu FB, Cai L, Yu Z, Li H, Ye X, Qi Q, Wang J, Pan A, et al: Ferritin concentrations, metabolic syndrome, and type 2 diabetes in middle-aged and elderly chinese. J Clin Endocrinol Metab. 2008, 93 (12): 4690-4696. 10.1210/jc.2008-1159.CrossRefPubMed Sun L, Franco OH, Hu FB, Cai L, Yu Z, Li H, Ye X, Qi Q, Wang J, Pan A, et al: Ferritin concentrations, metabolic syndrome, and type 2 diabetes in middle-aged and elderly chinese. J Clin Endocrinol Metab. 2008, 93 (12): 4690-4696. 10.1210/jc.2008-1159.CrossRefPubMed
24.
go back to reference Jin D, Guo H, Bu SY, Zhang Y, Hannaford J, Mashek DG, Chen X: Lipocalin 2 is a selective modulator of peroxisome proliferator-activated receptor-gamma activation and function in lipid homeostasis and energy expenditure. FASEB J. 2011, 25 (2): 754-764. 10.1096/fj.10-165175.PubMedCentralCrossRefPubMed Jin D, Guo H, Bu SY, Zhang Y, Hannaford J, Mashek DG, Chen X: Lipocalin 2 is a selective modulator of peroxisome proliferator-activated receptor-gamma activation and function in lipid homeostasis and energy expenditure. FASEB J. 2011, 25 (2): 754-764. 10.1096/fj.10-165175.PubMedCentralCrossRefPubMed
25.
go back to reference Jun LS, Siddall CP, Rosen ED: A minor role for lipocalin 2 in high-fat diet-induced glucose intolerance. Am J Physiol Endocrinol Metab. 2011, 301 (5): E825-E835. 10.1152/ajpendo.00147.2011.PubMedCentralCrossRefPubMed Jun LS, Siddall CP, Rosen ED: A minor role for lipocalin 2 in high-fat diet-induced glucose intolerance. Am J Physiol Endocrinol Metab. 2011, 301 (5): E825-E835. 10.1152/ajpendo.00147.2011.PubMedCentralCrossRefPubMed
26.
go back to reference Alvehus M, Buren J, Sjostrom M, Goedecke J, Olsson T: The human visceral fat depot has a unique inflammatory profile. Obesity (Silver Spring). 2010, 18 (5): 879-883. 10.1038/oby.2010.22.CrossRef Alvehus M, Buren J, Sjostrom M, Goedecke J, Olsson T: The human visceral fat depot has a unique inflammatory profile. Obesity (Silver Spring). 2010, 18 (5): 879-883. 10.1038/oby.2010.22.CrossRef
27.
go back to reference Zhang J, Wu Y, Zhang Y, Leroith D, Bernlohr DA, Chen X: The role of lipocalin 2 in the regulation of inflammation in adipocytes and macrophages. Mol Endocrinol. 2008, 22 (6): 1416-1426. 10.1210/me.2007-0420.PubMedCentralCrossRefPubMed Zhang J, Wu Y, Zhang Y, Leroith D, Bernlohr DA, Chen X: The role of lipocalin 2 in the regulation of inflammation in adipocytes and macrophages. Mol Endocrinol. 2008, 22 (6): 1416-1426. 10.1210/me.2007-0420.PubMedCentralCrossRefPubMed
28.
go back to reference Kratchmarova I, Kalume DE, Blagoev B, Scherer PE, Podtelejnikov AV, Molina H, Bickel PE, Andersen JS, Fernandez MM, Bunkenborg J, et al: A proteomic approach for identification of secreted proteins during the differentiation of 3 T3-L1 preadipocytes to adipocytes. Mol Cell Proteomics. 2002, 1 (3): 213-222. 10.1074/mcp.M200006-MCP200.CrossRefPubMed Kratchmarova I, Kalume DE, Blagoev B, Scherer PE, Podtelejnikov AV, Molina H, Bickel PE, Andersen JS, Fernandez MM, Bunkenborg J, et al: A proteomic approach for identification of secreted proteins during the differentiation of 3 T3-L1 preadipocytes to adipocytes. Mol Cell Proteomics. 2002, 1 (3): 213-222. 10.1074/mcp.M200006-MCP200.CrossRefPubMed
29.
go back to reference Teixeira-Lemos E, Nunes S, Teixeira F, Reis F: Regular physical exercise training assists in preventing type 2 diabetes development: focus on its antioxidant and anti-inflammatory properties. Cardiovasc Diabetol. 2011, 10: 12-10.1186/1475-2840-10-12.PubMedCentralCrossRefPubMed Teixeira-Lemos E, Nunes S, Teixeira F, Reis F: Regular physical exercise training assists in preventing type 2 diabetes development: focus on its antioxidant and anti-inflammatory properties. Cardiovasc Diabetol. 2011, 10: 12-10.1186/1475-2840-10-12.PubMedCentralCrossRefPubMed
30.
go back to reference Haffner SM: The metabolic syndrome: inflammation, diabetes mellitus, and cardiovascular disease. Am J Cardiol. 2006, 97 (2A): 3A-11A.CrossRefPubMed Haffner SM: The metabolic syndrome: inflammation, diabetes mellitus, and cardiovascular disease. Am J Cardiol. 2006, 97 (2A): 3A-11A.CrossRefPubMed
31.
go back to reference Tsimikas S, Willerson JT, Ridker PM: C-reactive protein and other emerging blood biomarkers to optimize risk stratification of vulnerable patients. J Am Coll Cardiol. 2006, 47 (8 Suppl): C19-C31.CrossRefPubMed Tsimikas S, Willerson JT, Ridker PM: C-reactive protein and other emerging blood biomarkers to optimize risk stratification of vulnerable patients. J Am Coll Cardiol. 2006, 47 (8 Suppl): C19-C31.CrossRefPubMed
32.
go back to reference Chavey C, Lazennec G, Lagarrigue S, Clape C, Iankova I, Teyssier J, Annicotte JS, Schmidt J, Mataki C, Yamamoto H, et al: CXC ligand 5 is an adipose-tissue derived factor that links obesity to insulin resistance. Cell Metab. 2009, 9 (4): 339-349. 10.1016/j.cmet.2009.03.002.PubMedCentralCrossRefPubMed Chavey C, Lazennec G, Lagarrigue S, Clape C, Iankova I, Teyssier J, Annicotte JS, Schmidt J, Mataki C, Yamamoto H, et al: CXC ligand 5 is an adipose-tissue derived factor that links obesity to insulin resistance. Cell Metab. 2009, 9 (4): 339-349. 10.1016/j.cmet.2009.03.002.PubMedCentralCrossRefPubMed
Metadata
Title
Lipocalin-2, glucose metabolism and chronic low-grade systemic inflammation in Chinese people
Authors
Ying Huang
Zhen Yang
Zi Ye
Qin Li
Jie Wen
Xiaoming Tao
Lili Chen
Min He
Xuanchun Wang
Bin Lu
Zhaoyun Zhang
Weiwei Zhang
Shen Qu
Renming Hu
Publication date
01-12-2012
Publisher
BioMed Central
Published in
Cardiovascular Diabetology / Issue 1/2012
Electronic ISSN: 1475-2840
DOI
https://doi.org/10.1186/1475-2840-11-11

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