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

Springer Science and Business Media LLC - Tập 11 - Trang 1-8 - 2012
Ying Huang1, Zhen Yang2, Zi Ye1, Qin Li1, Jie Wen1, Xiaoming Tao1, Lili Chen1, Min He1, Xuanchun Wang1, Bin Lu1, Zhaoyun Zhang1, Weiwei Zhang3, Shen Qu2, Renming Hu1
1Institute of Endocrinology and Diabetology, Huashan hospital, Shanghai Medical College, Fudan University, Shanghai, China
2Department of Endocrinology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China
3Department of Endocrinology, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China

Tóm tắt

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. 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. 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). Our findings suggest that elevated serum lipocalin-2 is closely and independently associated with impaired glucose regulation and type 2 diabetes.

Tài liệu tham khảo

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. Rasouli N, Kern PA: Adipocytokines and the metabolic complications of obesity. J Clin Endocrinol Metab. 2008, 93 (11 Suppl 1): S64-S73. Fernandez-Real JM, Ricart W: Insulin resistance and chronic cardiovascular inflammatory syndrome. Endocr Rev. 2003, 24 (3): 278-301. 10.1210/er.2002-0010. 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. 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. Flower DR: The up-and-down beta-barrel proteins: three of a kind. FASEB J. 1995, 9 (7): 566-567. 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. 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. 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. 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. 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. 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. 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. 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. 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. American Diabetes Association: Diagnosis and classification of diabetes mellitus. Diabetes Care. 2005, 28: S37-S42. 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. 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. 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. 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. Farrell PA, Beard JL, Druckenmiller M: Increased insulin sensitivity in iron-deficient rats. J Nutr. 1988, 118 (9): 1104-1109. 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. 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. 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. 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. 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. 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. 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. 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. Haffner SM: The metabolic syndrome: inflammation, diabetes mellitus, and cardiovascular disease. Am J Cardiol. 2006, 97 (2A): 3A-11A. 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. 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.