Horm Metab Res 2007; 39(10): 758-763
DOI: 10.1055/s-2007-990288
Clinical Human

© Georg Thieme Verlag KG Stuttgart · New York

Visfatin, TNF-α and IL-6 mRNA Expression is Increased in Mononuclear Cells from Type 2 Diabetic Women

P. C. Tsiotra 1 , C. Tsigos 1 , E. Yfanti 1 , E. Anastasiou 2 , M. Vikentiou 3 , K. Psarra 3 , C. Papasteriades 3 , S. A. Raptis 1
  • 1Hellenic National Center for the Research, Prevention and Treatment of Diabetes Mellitus and its Complications (H.N.D.C), Athens, Greece
  • 2First Endocrine Section and Diabetes Centre, “Alexandra” Hospital, Athens, Greece
  • 3Department of Immunology and Histocompatibility, “Evangelismos” General Hospital, Athens, Greece
Further Information

Publication History

Received 02.04.2007

Accepted 05.07.2007

Publication Date:
22 October 2007 (online)

Abstract

Visfatin, is a new adipokine, highly expressed in the visceral fat of both mice and humans. To examine whether visfatin is expressed in human peripheral monocyte-enriched mononuclear cells and whether its expression is altered in type 2 diabetes (DM2), we compared 24 DM2 women [17 overweight (BMI >25) and 7 lean (BMI<25)] to 26 healthy women (14 overweight and 12 lean), all premenopausal. Relative visfatin mRNA levels were significantly higher (approximately 3-fold) in DM2 compared to healthy control women (p<0.02), independently of the presence of overweight/obesity. Mononuclear TNF-α and IL-6 mRNA expression was also elevated in DM2 compared to control women (p=0.001 and p=0.004, respectively), an increase observed in both lean and overweight DM2 women. By contrast, circulating visfatin, TNF-α, and IL-6 levels showed no difference between DM2 and control women, while adiponectin plasma levels were significantly decreased in the DM2 women (p<0.001). Circulating visfatin and TNF-α levels did not differ either between the lean and the overweight subgroups of DM2 and control women, while IL-6 plasma levels were significantly higher in both overweight subgroups compared to their lean counterparts. In conclusion, visfatin, TNF-α, and IL-6 mRNA expressions are increased in peripheral mononuclear-monocytic cells from women with type 2 diabetes, independent of their BMI, which may enhance the effects of their adipose-derived levels and may contribute to the increased insulin resistance and atherogenic risk of these patients.

References

  • 1 Fantuzzi G. Adipose tissue, adipokines, and inflammation.  J Allergy Clin Immunol. 2005;  115 911-919
  • 2 Rajala MW, Scherer PE. Minireview: The adipocyte-at the crossroads of energy homeostasis, inflammation, and atherosclerosis.  Endocrinology. 2003;  144 3765-3773
  • 3 Arner P. The adipocyte in insulin resistance: key molecules and the impact of the thiazolidinediones.  Trends Endocrinol Metab. 2003;  14 137-145
  • 4 Samal B, Sun Y, Stearns G, Xie C, Suggs S, MacNiece I. Cloning and characterization of the cDNA encoding a novel human pre-B-cell-colony-enhancing factor.  Mol Cell Biol. 1994;  14 1431-1437
  • 5 Chen MP, Chung FM, Chang DM, Tsai JC, Huang HF, Shin SJ, Lee YJ. Elevated plasma level of visfatin/PBEF/pre-B cell colony-enhancing factor in patients with type 2 diabetes mellitus.  J Clin Endocrinol Metab. 2006;  91 295-299
  • 6 Fukuhara A, Matsuda M, Nishizawa M, Segawa K, Tanaka M, Kishimoto K, Matsuki Y, Murakami M, Ichisaka T, Murakami H, Watanabe E, Takagi T, Akiyoshi M, Ohtsubo T, Kihara S, Yamashita S, Makishima M, Funahashi T, Yamanaka S, Hiramatsu R, Matsuzawa Y, Shimomura I. Visfatin: a protein secreted by visceral fat that mimics the effects of insulin.  Science. 2005;  307 426-430
  • 7 Sethi JK, Vidal-Puig A. Visfatin: the missing link between intra-abdominal obesity and diabetes?.  Trends Mol Med. 2005;  11 344-347
  • 8 Arner P. Visfatin - a true or false trail to type 2 diabetes mellitus.  J Clin Endocrinol Metab. 2006;  91 28-30
  • 9 Stephens JM, Vidal-Puig AJ. An update on visfatin/pre-B cell colony-enhancing factor, an ubiquitously expressed, illusive cytokine that is regulated in obesity.  Curr Opin Lipidol. 2006;  17 128-131
  • 10 Hammarstedt A, Pihlajamaki J, Sopasakis VR, Gogg S, Jansson PA, Laakso M, Smith U. Visfatin is an adipokine but it is not regulated by thiazolidinediones.  J Clin Endocrinol Metab. 2006;  91 1181-1184
  • 11 Haider DG, Schindler K, Schaller G, Prager G, Wolzt M, Ludvik B. Increased plasma visfatin concentrations in morbidly obese subjects are reduced after gastric banding.  J Clin Endocrinol Metab. 2006;  91 1578-1581
  • 12 Berndt J, Kloting N, Kralisch S, Kovacs P, Fasshauer M, Schon MR, Stumvoll M, Bluher M. Plasma visfatin concentrations and fat depot-specific mRNA expression in humans.  Diabetes. 2005;  54 2911-2916
  • 13 Pagano C, Pilon C, Olivieri M, Mason P, Fabris R, Serra R, Milan G, Rossato M, Federspil G, Vettor R. Reduced plasma visfatin/pre-B cell colony-enhancing factor in obesity is not related to Insulin Resistance in Humans.  J Clin Endocrinol Metab. 2006;  91 3165-3170
  • 14 Jian WX, Luo TH, Gu YY, Zhang HL, Zheng S, Dai M, Han JF, Zhao Y, Li G, Luo M. The visfatin gene is associated with glucose and lipid metabolism in a Chinese population.  Diabet Med. 2006;  23 967-973
  • 15 Haider DG, Schaller G, Kapiotis S, Maier C, Luger A, Wolzt M. The release of the adipocytokine visfatin is regulated by glucose and insulin.  Diabetologia. 2006;  49 1909-1914
  • 16 Wellen KE, Hotamisligil GS. Inflammation, stress, and diabetes.  J Clin Invest. 2005;  115 1111-1119
  • 17 Xu H, Barnes GT, Yang Q, Tan G, Yang D, Chou CJ, Sole J, Nichols A, Ross JS, Tartaglia LA, Chen H. Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance.  J Clin Invest. 2003;  112 1821-1830
  • 18 Curat CA, Wegner V, Sengenes C, Miranville A, Tonus C, Busse R, Bouloumie A. Macrophages in human visceral adipose tissue: increased accumulation in obesity and a source of resistin and visfatin.  Diabetologia. 2006;  49 744-747
  • 19 Hotamisligil GS, Arner P, Caro JF, Atkinson RL, Spiegelman BM. Increased adipose tissue expression of tumor necrosis factor-alpha in human obesity and insulin resistance.  J Clin Invest. 1995;  95 2409-2415
  • 20 Mohamed-Ali V, Goodrick S, Rawesh A, Katz DR, Miles JM, Yudkin JS, Klein S, Coppack SW. Subcutaneous adipose tissue releases interleukin-6, but not tumor necrosis factor-alpha, in vivo.  J Clin Endocrinol Metab. 1997;  82 4196-4200
  • 21 Bastard JP, Jardel C, Bruckert E, Blondy P, Capeau J, Laville M, Vidal H, Hainque B. Elevated levels of interleukin 6 are reduced in serum and subcutaneous adipose tissue of obese women after weight loss.  J Clin Endocrinol Metab. 2000;  85 3338-3342
  • 22 Ognjanovic S, Bao S, Yamamoto SY, Garibay-Tupas J, Samal B, Bryant-Greenwood GD. Genomic organization of the gene coding for human pre-B-cell colony enhancing factor and expression in human fetal membranes.  J Mol Endocrinol. 2001;  26 107-117
  • 23 Kralisch S, Klein J, Lossner U, Bluher M, Paschke R, Stumvoll M, Fasshauer M. Hormonal regulation of the novel adipocytokine visfatin in 3T3-L1 adipocytes.  J Endocrinol. 2005;  185 R1-R8
  • 24 Kralisch S, Klein J, Lossner U, Bluher M, Paschke R, Stumvoll M, Fasshauer M. Interleukin-6 is a negative regulator of visfatin gene expression in 3T3-L1 adipocytes.  Am J Physiol Endocrinol Metab. 2005;  289 E586-E590
  • 25 Ye SQ, Simon BA, Maloney JP, Zambelli-Weiner A, Gao L, Grant A, Easley RB, MacVerry BJ, Tuder RM, Standiford T, Brower RG, Barnes KC, Garcia JG. Pre-B-cell colony-enhancing factor as a potential novel biomarker in acute lung injury.  Am J Respir Crit Care Med. 2005;  171 361-370
  • 26 Jia SH, Li Y, Parodo J, Kapus A, Fan L, Rotstein OD, Marshall JC. Pre-B cell colony-enhancing factor inhibits neutrophil apoptosis in experimental inflammation and clinical sepsis.  J Clin Invest. 2004;  113 1318-1327
  • 27 Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man.  Diabetologia. 1985;  28 412-419
  • 28 Tsiotra PC, Pappa V, Raptis SA, Tsigos C. Expression of the long and short leptin receptor isoforms in peripheral blood mononuclear cells: implications for leptin's actions.  Metabolism. 2000;  49 1537-1541
  • 29 Wong LM, Medrano FJ. Real-time PCR for mRNA quantitation.  Biotechniques. 2005;  39 75-85
  • 30 Kitani T, Okuno S, Fujisawa H. Growth phase-dependent changes in the subcellular localization of pre-B-cell colony-enhancing factor.  FEBS Lett. 2003;  544 74-78
  • 31 Weisberg SP, MacCann D, Desai M, Rosenbaum M, Leibel RL, Ferrante Jr AW. Obesity is associated with macrophage accumulation in adipose tissue.  J Clin Invest. 2003;  112 1796-1808

Correspondence

P. C. TsiotraPhD 

Molecular Biology Laboratory

Hellenic National Center for the Research

Prevention and Treatment of Diabetes Mellitus and its Complications (H.N.D.C)

Ploutarchou 3

10675 Athens

Greece

Phone: +30/210/583 24 85

Phone: 210/729 51 60

Fax: +30/210/532 64 54

Fax: 210/729 51 68

Email: ytsiotra@hndc.gr