Original Article

Effect of Omega-3 Supplementation on Lipocalin 2 and Retinol-Binding Protein 4 in Type 2 Diabetic Patients

Abstract

Background: Serum levels of lipocalin 2 (LCN 2) and retinol-binding protein-4 (RBP 4), increase in type 2 diabetes mellitus (T2DM). We sought to determine whether serum LCN 2 and RBP 4 change after an intervention with omega-3 fatty acids supplementation in diabetic patients.

Methods: Forty-five type 2 diabetic patients from Iranian Diabetic Association in Tehran, Iran in 2013 were randomly recruited into two groups: one group received 4 g/d omega-3 for 10 wk; and the control group received placebo. Blood samples, food intake records, anthropometric measurements were obtained from all participants at the beginning and end of the study.

Results: Fasting RBP 4 plasma levels significantly changed after 10 wk supplementation (P = 0.01). The LCN 2 concentrations decreased in omega-3 group, but the changes were not statistically significant. Omega-3 supplementation had no noticeable effect on anthropometric factors.

Conclusions: These findings provide a rationale for omega-3 supplements aimed at lowering serum RBP 4 levels in T2DM.

 

Kehrer JP (2010). Lipocalin-2: pro- or anti-apoptotic? Cell Biol Toxicol, 26:83-9.

Miharada K, Hiroyama T, Sudo K, Nagasawa T, Nakamura Y (2005). Lipocalin 2 functions as a negative regulator of red blood cell production in an autocrine fashion. FASEB J, 19:1881-3.

Stejskal D, Karpisek M, Humenanska V, Hanulova Z, Stejskal P, Kusnierova P, Petzel M (2008). Lipocalin-2: development, analytical characterization, and clinical testing of a new ELISA. Horm Metab Res, 40:381-5.

Yan QW, Yang Q, Mody N, Graham TE, Hsu CH, Xu Z, Houstis NE, Kahn BB, Rosen ED (2007). The adipokine lipocalin 2 is regulated by obesity and promotes insulin resistance. Diabetes, 56:2533-40.

Tan BK, Adya R, Shan X, Syed F, Lewandowski KC, O'Hare JP, Randeva HS (2009). Ex vivo and in vivo regulation of lipocalin-2, a novel adipokine, by insulin. Diabetes Care, 32:129-31.

Flower DR (1996). The lipocalin protein family: structure and function. Biochem J, 318 ( Pt 1):1-14.

Duggirala R, Blangero J, Almasy L, Dyer TD, Williams KL, Leach RJ, O'Connell P, Stern MP (1999). Linkage of type 2 diabetes mellitus and of age at onset to a genetic location on chromosome 10q in Mexican Americans. Am J Hum Genet, 64:1127-40.

Meigs JB, Panhuysen CI, Myers RH, Wilson PW, Cupples LA (2002). A genome-wide scan for loci linked to plasma levels of glucose and HbA(1c) in a community-based sample of Caucasian pedigrees: The Framingham Offspring Study. Diabetes, 51:833-40.

Colantuoni V, Romano V, Bensi G, Santoro C, Costanzo F, Raugei G, Cortese R (1983). Cloning and sequencing of a full length cDNA coding for human retinol-binding protein. Nucleic Acids Res, 11:7769-76.

Jaconi S, Rose K, Hughes GJ, Saurat JH, Siegenthaler G (1995). Characterization of two post-translationally processed forms of human serum retinol-binding protein: altered ratios in chronic renal failure. J Lipid Res, 36:1247-53.

Mallat Z, Simon T, Benessiano J, Clement K, Taleb S, Wareham NJ, Luben R, Khaw KT, Tedgui A, Boekholdt SM (2009). Retinol-binding protein 4 and prediction of incident coronary events in healthy men and women. J Clin Endocrinol Metab, 94:255-60.

Sasaki M, Otani T, Kawakami M, Ishikawa SE (2010). Elevation of plasma retinol-binding protein 4 and reduction of plasma adiponectin in subjects with cerebral infarction. Metabolism, 59:527-32.

Ingelsson E, Sundstrom J, Melhus H, Michaelsson K, Berne C, Vasan RS, Riserus U, Blomhoff R, Lind L, Arnlov J (2009). Circulating retinol-binding protein 4, cardiovascular risk factors and prevalent cardiovascular disease in elderly. Atherosclerosis, 206:239-44.

Promintzer M, Krebs M, Todoric J, Luger A, Bischof MG, Nowotny P, Wagner O, Esterbauer H, Anderwald C (2007). Insulin resistance is unrelated to circulating retinol binding protein and protein C inhibitor. J Clin Endocrinol Metab, 92:4306-12.

Broch M, Vendrell J, Ricart W, Richart C, Fernandez-Real JM (2007). Circulating retinol-binding protein-4, insulin sensitivity, insulin secretion, and insulin disposition index in obese and nonobese subjects. Diabetes Care, 30:1802-6.

Haider DG, Schindler K, Prager G, Bohdjalian A, Luger A, Wolzt M, Ludvik B (2007). Serum retinol-binding protein 4 is reduced after weight loss in morbidly obese subjects. J Clin Endocrinol Metab, 92:1168-71.

Graham TE, Yang Q, Bluher M, Hammarstedt A, Ciaraldi TP, Henry RR, Wason CJ, Oberbach A, Jansson PA, Smith U, Kahn BB (2006). Retinol-binding protein 4 and insulin resistance in lean, obese, and diabetic subjects. N Engl J Med, 354:2552-63.

Yang Q, Graham TE, Mody N, Preitner F, Peroni OD, Zabolotny JM, Kotani K, Quadro L, Kahn BB (2005). Serum retinol binding protein 4 contributes to insulin resistance in obesity and type 2 diabetes. Nature, 436:356-62.

Zheng JS, Huang T, Yang J, Fu YQ, Li D (2012). Marine N-3 polyunsaturated fatty acids are inversely associated with risk of type 2 diabetes in Asians: a systematic review and meta-analysis. PLoS One, 7:e44525.

Magee P, Pearson S, Whittingham-Dowd J, Allen J (2012). PPARgamma as a molecular target of EPA anti-inflammatory activity during TNF-alpha-impaired skeletal muscle cell differentiation. J Nutr Biochem, 23:1440-8.

Drevon CA (2005). Fatty acids and expression of adipokines. Biochim Biophys Acta, 1740:287-92.

Lee JY, Zhao L, Youn HS, Weatherill AR, Tapping R, Feng L, Lee WH, Fitzgerald KA, Hwang DH (2004). Saturated fatty acid activates but polyunsaturated fatty acid inhibits Toll-like receptor 2 dimerized with Toll-like receptor 6 or 1. J Biol Chem, 279:16971-9.

Serhan CN, Chiang N, Van Dyke TE (2008). Resolving inflammation: dual anti-inflammatory and pro-resolution lipid mediators. Nat Rev Immunol, 8:349-61.

Liu X, Hamnvik OP, Petrou M, Gong H, Chamberland JP, Christophi CA, Kales SN, Christiani DC, Mantzoros CS (2011). Circulating lipocalin 2 is associated with body fat distribution at baseline but is not an independent predictor of insulin resistance: the prospective Cyprus Metabolism Study. Eur J Endocrinol, 165:805-12.

Huang Y, Yang Z, Ye Z, Li Q, Wen J, Tao X, Chen L, He M, Wang X, Lu B, Zhang Z, Zhang W, Qu S, Hu R (2012). Lipocalin-2, glucose metabolism and chronic low-grade systemic inflammation in Chinese people. Cardiovasc Diabetol, 11:11.

Derosa G, Cicero AF, D'Angelo A, Fogari E, Maffioli P (2012). Effects of 1-year orlistat treatment compared to placebo on insulin resistance parameters in patients with type 2 diabetes. J Clin Pharm Ther, 37:187-95.

Derosa G, Maffioli P, D'Angelo A, Fogari E, Bianchi L, Cicero AF (2011). Acarbose on insulin resistance after an oral fat load: a double-blind, placebo controlled study. J Diabetes Complications, 25:258-66.

Pan A, Demark-Wahnefried W, Ye X, Yu Z, Li H, Qi Q, Sun J, Chen Y, Chen X, Liu Y, Lin X (2009). Effects of a flaxseed-derived lignan supplement on C-reactive protein, IL-6 and retinol-binding protein 4 in type 2 diabetic patients. Br J Nutr, 101:1145-9.

Takebayashi K, Suetsugu M, Wakabayashi S, Aso Y, Inukai T (2007). Retinol binding protein-4 levels and clinical features of type 2 diabetes patients. J Clin Endocrinol Metab, 92:2712-9.

Lin KD, Chang YH, Wang CL, Yang YH, Hsiao PJ, Li TH, Shin SJ (2008). Thiazolidinedione addition reduces the serum retinol-binding protein 4 in type 2 diabetic patients treated with metformin and sulfonylurea. Transl Res, 151:309-14.

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IssueVol 45 No 1 (2016) QRcode
SectionOriginal Article(s)
Keywords
Omega-3 fatty acid Lipocalin Retinol-binding protein Diabetes mellitus

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How to Cite
1.
FARAHBAKHSH-FARSI P, DJAZAYERY A, ESHRAGHIAN MR, KOOHDANI F, ZAREI M, JA­VANBAKHTMH, DERAKHSHANIAN H, DJALALI M. Effect of Omega-3 Supplementation on Lipocalin 2 and Retinol-Binding Protein 4 in Type 2 Diabetic Patients. Iran J Public Health. 2016;45(1):63-69.