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DOI: 10.1055/s-0029-1243638
© Georg Thieme Verlag KG Stuttgart · New York
Visfatin/PBEF/Nampt and Resistin Expressions in Circulating Blood Monocytes are Differentially Related to Obesity and Type 2 Diabetes in Humans
Publication History
received 17.08.2009
accepted 08.12.2009
Publication Date:
20 January 2010 (online)
![](https://www.thieme-connect.de/media/hmr/201004/lookinside/thumbnails/10.1055-s-0029-1243638-1.jpg)
Abstract
Low-grade inflammation is important in the development of obesity related pathologies such as insulin resistance and type 2 diabetes, and also cardiovascular disease. Visfatin/PBEF/Nampt and resistin are proinflammatory adipokines secreted from adipocytes, monocytes, and macrophages, and have been linked to atherosclerotic plaque formation, recently. The aim of the present study was to investigate if the expression of these molecules in circulating blood monocytes is altered in obese and/or type 2 diabetic human subjects. Monocytes were isolated by CD14-antibody based magnetic cell sorting from blood samples of 17 lean controls, 20 obese nondiabetic subjects, and 19 obese patients with type 2 diabetes. FACS analysis was performed to test purity of the cell preparations. Expression of the different adipokines was measured by multiplex real-time PCR on RNA-level. Visfatin/PBEF/Nampt was found to be very strongly expressed in monocytes, whereas resistin levels were significantly lower. Furthermore, visfatin/PBEF/Nampt expression was significantly upregulated in obese type 2 diabetic patients, whereas obese nondiabetics exhibited similar levels compared to lean controls, indicating that visfatin/PBEF/Nampt levels are related to type 2 diabetes rather than to obesity. In contrast, resistin expression displayed a different pattern being significantly increased in obese subjects compared to controls but not related to type 2 diabetes. These data suggest a differential role for these two proinflammatory adipokines in linking metabolic diseases to atherosclerosis with visfatin/PBEF/Nampt being more important in patients with type 2 diabetes and resistin in obese but nondiabetic human subjects.
Key words
inflammation - insulin resistance - atherosclerosis
References
- 1 Golden SH, Robinson KA, Saldanha I, Anton B, Ladenson PW. Clinical review: Prevalence and incidence of endocrine and metabolic disorders in the United States: a comprehensive review. J Clin Endocrinol Metab. 2009; 94 1853-1878
- 2 Katagiri H, Yamada T, Oka Y. Adiposity and cardiovascular disorders: disturbance of the regulatory system consisting of humoral and neuronal signals. Circ Res. 2007; 101 27-39
- 3 Yamagishi S, Nakamura K, Matsui T, Takenaka K, Jinnouchi Y, Imaizumi T. Cardiovascular disease in diabetes. Mini Rev Med Chem. 2006; 6 313-318
- 4 Kanda H, Tateya S, Tamori Y, Kotani K, Hiasa K, Kitazawa R, Kitazawa S, Miyachi H, Maeda S, Egashira K, Kasuga M. MCP-1 contributes to macrophage infiltration into adipose tissue, insulin resistance, and hepatic steatosis in obesity. J Clin Invest. 2006; 116 1494-1505
- 5 Tilg H, Moschen AR. Inflammatory mechanism in the regulation of insulin resistance. Mol Med. 2008; 14 222-231
- 6 Gerrity RG, Naito HK, Richardson M, Schwartz CJ. Dietary induced atherogenesis in swine. Morphology of the intima in prelesion stages. Am J Pathol. 1979; 95 775-792
- 7 Cybulsky MI, Iiyama K, Li H, Zhu S, Chen M, Iiyama M, Davis V, Gutierrez-Ramos JC, Connelly PW, Milstone DS. A major role for VCAM-1, but not ICAM-1, in early atherosclerosis. J Clin Invest. 2001; 107 1255-1262
- 8 Byrne GI, Kalayoglu MV. Chlamydia pneumoniae and atherosclerosis: links to the disease process. Am Heart J. 1999; 138 488-490
- 9 Laudes M, Oberhauser F, Bilkovski R, Schubert M, Udelhoven M, Wassmer G, Roth B, Krone W. Human fetal adiponectin and retinol-binding protein (RBP)-4 levels in relation to birth weight and maternal obesity. Exp Clin Endocrinol Diabetes. 2009; 117 146-149
- 10 Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM. Positional cloning of the mouse obese gene and its human homologue. Nature. 1994; 372 425-432
- 11 La Cava A, Alviggi C, Matarese G. Unraveling the multiple roles of leptin in inflammation and autoimmunity. J Mol Med. 2004; 82 4-11
- 12 Samal B, Sun Y, Stearns G, Xie C, Suggs S, McNiece I. Cloning and characterization of the cDNA encoding a novel human pre-B-cell colony-enhancing factor. Mol Cell Biol. 1994; 14 1431-1437
- 13 Takebayashi K, Suetsugu M, Wakabayashi S, Aso Y, Inukai T. Association between plasma visfatin/PBEF/Nampt and vascular endothelial function in patients with type 2 diabetes mellitus. Metabolism. 2007; 56 451-458
- 14 Böttcher Y, Teupser D, Enigk B, Berndt J, Klöting N, Schön MR, Thiery J, Blüher M, Stumvoll M, Kovacs P. Genetic variation in the visfatin/PBEF/Nampt gene (PBEF1) and its relation to glucose metabolism and fat-depot-specific messenger ribonucleic acid expression in humans. J Clin Endocrinol Metab. 2006; 91 2725-2731
- 15 Steppan CM, Bailey ST, Bhat S, Brown EJ, Banerjee RR, Wright CM, Patel HR, Ahima RS, Lazar MA. The hormone resistin links obesity to diabetes. Nature. 2001; 409 307-312
- 16 Kawanami D, Maemura K, Takeda N, Harada T, Nojiri T, Imai Y, Manabe I, Utsunomiya K, Nagai R. Direct reciprocal effects of resistin and adiponectin on vascular endothelial cells: a new insight into adipocytokine-endothelial cell interactions. Biochem Biophys Res Commun. 2004; 314 415-419
- 17 Ayoub SS, Botting RM, Joshi AN, Seed MP, Colville-Nash PR. Activation of macrophage peroxisome proliferator-activated receptor-gamma by diclofenac results in the induction of cyclooxygenase-2 protein and the synthesis of anti-inflammatory cytokines. Mol Cell Biochem. 2009; 327 101-110
- 18 Laudes M, Bilkovski R, Oberhauser F, Droste A, Gomolka M, Leeser U, Udelhoven M, Krone W. Transcription Factor FBI-1 acts as a dual regulator in adipogenesis by coordinated regulation of cyclin A and E2F-4. J Mol Med. 2008; 86 597-608
- 19 Yamagata S, Tomita K, Sato R, Niwa A, Higashino H, Tohda Y. Interleukin-18-deficient mice exhibit diminished chronic inflammation and airway remodelling in ovalbumin-induced asthma model. Clin Exp Immunol.. 2008; 154 295-304
- 20 Lazar MA. Resistin- and obesity-associated metabolic diseases. Horm Metab Res. 2007; 39 710-716
- 21 Wang T, Zhang X, Bheda P, Revollo JR, Imai S, Wolberger C. Structure of Nampt/PBEF/visfatin/PBEF/Nampt, a mammalian NAD+ biosynthetic enzyme. Nat Struct Mol Biol. 2006; 13 661-662
- 22 Revollo JR, Grimm AA, Imai S. The NAD biosynthesis pathway mediated by nicotinamide phosphoribosyltransferase regulates Sir2 activity in mammalian cells. J Biol Chem. 2004; 279 50754-50763
- 23 Moschen AR, Kaser A, Enrich B, Mosheimer B, Theurl M, Niederegger H, Tilg H. Visfatin/PBEF/Nampt, an adipocytokine with proinflammatory and immunomodulating properties. J Immunol. 2007; 178 1748-1758
- 24 Nowell MA, Richards PJ, Fielding CA, Ognjanovic S, Topley N, Williams AS, Bryant-Greenwood G, Jones SA. Regulation of pre-B cell colony-enhancing factor by STAT-3-dependent interleukin-6 trans-signaling: implications in the pathogenesis of rheumatoid arthritis. Arthritis Rheum. 2006; 54 2084-2095
- 25 Otero M, Lago R, Gomez R, Lago F, Dieguez C, Gómez-Reino JJ, Gualillo O. Changes in plasma levels of fat-derived hormones adiponectin, leptin, resistin and visfatin/PBEF/Nampt in patients with rheumatoid arthritis. Ann Rheum Dis. 2006; 65 1198-1201
- 26 Oki K, Yamane K, Kamei N, Nojima H, Kohno N. Circulating visfatin/PBEF/Nampt level is correlated with inflammation, but not with insulin resistance. Clin Endocrinol (Oxf). 2007; 67 796-800
- 27 Xie H, Tang SY, Luo XH, Huang J, Cui RR, Yuan LQ, Zhou HD, Wu XP, Liao EY. Insulin-like effects of visfatin/PBEF/Nampt on human osteoblasts. Calcif Tissue Int. 2007; 80 201-210
- 28 Dogru T, Sonmez A, Tasci I, Bozoglu E, Yilmaz MI, Genc H, Erdem G, Gok M, Bingol N, Kilic S, Ozgurtas T, Bingol S. Plasma visfatin/PBEF/Nampt levels in patients with newly diagnosed and untreated type 2 diabetes mellitus and impaired glucose tolerance. Diabetes Res Clin Pract. 2007; 76 24-29
- 29 Krzyzanowska K, Krugluger W, Mittermayer F, Rahman R, Haider D, Shnawa N, Schernthaner G. Increased visfatin/PBEF/Nampt concentrations in women with gestational diabetes mellitus. Clin Sci (Lond). 2006; 110 605-609
- 30 Chan TF, Chen YL, Chen HH, Lee CH, Jong SB, Tsai EM. Increased plasma visfatin/PBEF/Nampt concentrations in women awith polycystic ovary syndrome. Fertil Steril. 2007; 88 401-405
- 31 Sommer G, Garten A, Petzold S, Beck-Sickinger AG, Blüher M, Stumvoll M, Fasshauer M. Visfatin/PBEF/Nampt/PBEF/Nampt: structure, regulation and potential function of a novel adipokine. Clin Sci (Lond). 2008; 115 13-23
- 32 Dahl TB, Yndestad A, Skjelland M, Øie E, Dahl A, Michelsen A, Damås JK, Tunheim SH, Ueland T, Smith C, Bendz B, Tonstad S, Gullestad L, Frøland SS, Krohg-Sørensen K, Russell D, Aukrust P, Halvorsen B. Increased expression of visfatin/PBEF/Nampt in macrophages of human unstable carotid and coronary atherosclerosis: possible role in inflammation and plaque destabilization. Circulation.. 2007; 115 972-980
- 33 Tsiotra PC, Tsigos C, Yfanti E, Anastasiou E, Vikentiou M, Psarra K, Papasteriades C, Raptis SA. Visfatin/PBEF/Nampt, TNF-alpha and IL-6 mRNA expression is increased in mononuclear cells from type 2 diabetic women. Horm Metab Res. 2007; 39 758-763
- 34 Savage DB, Sewter CP, Klenk ES, Segal DG, Vidal-Puig A, Considine RV, O’Rahilly S. Resistin/Fizz3 expression in relation to obesity and peroxisome proliferator-activated receptor-gamma action in humans. Diabetes. 2001; 50 2199-2202
- 35 Chen CC, Li TC, Li CI, Liu CS, Wang HJ, Lin CC. Serum resistin level among healthy subjects: relationship to anthropometric and metabolic parameters. Metabolism. 2005; 54 471-475
- 36 Lee JH, Chan JL, Yiannakouris N, Kontogianni M, Estrada E, Seip R, Orlova C, Mantzoros CS. Circulating resistin levels are not associated with obesity or insulin resistance in humans and are not regulated by fasting or leptin administration: cross-sectional and interventional studies in normal, insulin-resistant, and diabetic subjects. J Clin Endocrinol Metab. 2003; 88 4848-4856
- 37 Ohmori R, Momiyama Y, Kato R, Taniguchi H, Ogura M, Ayaori M, Nakamura H, Ohsuzu F. Associations between serum resistin levels and insulin resistance, inflammation, and coronary artery disease. J Am Coll Cardiol.. 2005; 46 379-380
- 38 Reilly MP, Lehrke M, Wolfe ML, Rohatgi A, Lazar MA, Rader DJ. Resistin is an inflammatory marker of atherosclerosis in humans. Circulation. 2005; 111 932-939
- 39 Díez JJ, Iglesias P, Fernández-Reyes MJ, Aguilera A, Bajo MA, Alvarez-Fidalgo P, Codoceo R, Selgas R. Serum concentrations of leptin, adiponectin and resistin, and their relationship with cardiovascular disease in patients with end-stage renal disease. Clin Endocrinol (Oxf). 2005; 62 242-249
- 40 Kougias P, Chai H, Lin PH, Yao Q, Lumsden AB, Chen C. Effects of adipocyte-derived cytokines on endothelial functions: implication of vascular disease. J Surg Res. 2005; 126 121-129
Correspondence
Dr. M. Laudes
Klinik II und Poliklinik für Innere Medizin
Zentrum für Molekulare Medizin
Universität zu Köln
Kerpner Straße 62
50924 Köln
Germany
Phone: +49/221/478 5481
Fax: +49/221/478 3107
Email: matthias.laudes@uk-koeln.de