Horm Metab Res 2018; 50(09): 653-660
DOI: 10.1055/a-0669-1584
Endocrine Care
© Georg Thieme Verlag KG Stuttgart · New York

Determinants of Visfatin/NAMPT Serum Concentration and its Leukocyte Expression in Hyperthyroidism

Nadia Sawicka-Gutaj
1   Department of Endocrinology, Metabolism and Internal Medicine, Poznan University of Medical Sciences, Poznań, Poland
,
Ariadna Zybek-Kocik
1   Department of Endocrinology, Metabolism and Internal Medicine, Poznan University of Medical Sciences, Poznań, Poland
,
Michał Kloska
2   Department of Gastroenterology, Metabolic Diseases and Dietetics, Poznan University of Medical Sciences, Poznań, Poland
,
Agata Czarnywojtek
1   Department of Endocrinology, Metabolism and Internal Medicine, Poznan University of Medical Sciences, Poznań, Poland
3   Department of Pharmacology, Poznan University of Medical Sciences, Poznań, Poland
,
Jerzy Sowiński
1   Department of Endocrinology, Metabolism and Internal Medicine, Poznan University of Medical Sciences, Poznań, Poland
,
Bartłomiej Budny
1   Department of Endocrinology, Metabolism and Internal Medicine, Poznan University of Medical Sciences, Poznań, Poland
,
Kosma Woliński
1   Department of Endocrinology, Metabolism and Internal Medicine, Poznan University of Medical Sciences, Poznań, Poland
,
Katarzyna Ziemnicka
1   Department of Endocrinology, Metabolism and Internal Medicine, Poznan University of Medical Sciences, Poznań, Poland
,
Dorota Mańkowska-Wierzbicka
2   Department of Gastroenterology, Metabolic Diseases and Dietetics, Poznan University of Medical Sciences, Poznań, Poland
,
Marek Ruchała
1   Department of Endocrinology, Metabolism and Internal Medicine, Poznan University of Medical Sciences, Poznań, Poland
› Author Affiliations
Further Information

Publication History

received 25 October 2017

accepted 31 July 2018

Publication Date:
05 September 2018 (online)

Abstract

We aimed to analyze the potential influence of thyroid autoimmunity on visfatin/NAMPT serum concentration and its leukocyte expression in hyperthyroid patients. This is a single-center, cross-sectional study with consecutive enrollment. All patients with newly diagnosed overt hyperthyroidism in a course of Graves' disease or toxic nodular goiter were included in the study. They underwent physical examination, laboratory investigation, body composition analysis, and thyroid ultrasound. NAMPT mRNA leukocyte expressions were measured using RT-qPCR. Of the 173 patients, 95 were enrolled in further analysis [67 patients with Graves' disease (GD) and 28 with toxic nodular goiter (TNG)]. Control group consisted of 43 healthy volunteers adjusted for age, sex, and BMI. Higher NAMPT/visfatin serum concentration was found in patients with GD comparing with patients with TNG (p=0.03855). We found significant NAMPT leukocyte overexpression in GD patients (n=32) as compared to TNG patients (n=18) and euthyroid controls (n=24) (p=0.005965). Simple linear regression analysis revealed that NAMPT/visfatin serum concentration was significantly associated with NAMPT leukocyte expression, thyroid autoimmunity, age, HOMA-IR, and fat mass percentage (FM%). NAMPT leukocyte expression was related to thyroid autoimmunity, age, and TRAb levels. The stepwise multiple regression analysis revealed FM% and HOMA-IR as independent predictors of visfatin/NAMPT serum levels. In a separate stepwise multiple regression analysis, we confirmed the association between NAMPT leukocyte expression and TRAb levels. We found that fat mass percentage together with HOMA-IR are the most significant predictors of visfatin/NAMPT serum elevation in hyperthyroid patients.

 
  • References

  • 1 Olszanecka-Glinianowicz M, Kocelak P, Nylec M, Chudek J, Zahorska-Markiewicz B. Circulating visfatin level and visfatin/insulin ratio in obese women with metabolic syndrome. Arch Med Sci 2012; 8: 214
  • 2 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
  • 3 Sandeep S, Velmurugan K, Deepa R, Mohan V. Serum visfatin in relation to visceral fat, obesity, and type 2 diabetes mellitus in Asian Indians. Metabolism 2007; 56: 565-570
  • 4 Hammarstedt A, Pihlajamaki J, Rotter Sopasakis V, 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
  • 5 Kowalska I, Straczkowski M, Nikolajuk A, Adamska A, Karczewska-Kupczewska M, Otziomek E, Wolczynski S, Gorska M. Serum visfatin in relation to insulin resistance and markers of hyperandrogenism in lean and obese women with polycystic ovary syndrome. Hum Reprod 2007; 22: 1824-1829
  • 6 Sawicka-Gutaj N, Waligorska-Stachura J, Andrusiewicz M, Biczysko M, Sowinski J, Skrobisz J, Ruchala M. Nicotinamide phosphorybosiltransferase overexpression in thyroid malignancies and its correlation with tumor stage and with survivin/survivin DEx3 expression. Tumour Biol 2015; 36: 7859-7863
  • 7 Bi TQ, Che XM. Nampt/PBEF/visfatin and cancer. Cancer Biol Ther 2010; 10: 119-125
  • 8 Fukuhara A, Matsuda M, Nishizawa M, Segawa K, Tanaka M, Kishimoto K, Matsuki Y, Murakami M, Ichisaka T, Murakami H. Visfatin: a protein secreted by visceral fat that mimics the effects of insulin. Science 2005; 307: 426-430
  • 9 Chen MP, Chung FM, Chang DM, Tsai JC, Huang HF, Shin SJ, Lee YJ. Elevated plasma level of visfatin/pre-B cell colony-enhancing factor in patients with type 2 diabetes mellitus. J Clin Endocrinol Metab 2006; 91: 295-299
  • 10 Chu C-H, Lee J-K, Wang M-C, Lu C-C, Sun C-C, Chuang M-J, Lam H-C. Change of visfatin, C-reactive protein concentrations, and insulin sensitivity in patients with hyperthyroidism. Metabolism 2008; 57: 1380-1383
  • 11 Caixas A, Tirado R, Vendrell J, Gallart L, Megia A, Simon I, Llaurado G, Gonzalez-Clemente JM, Gimenez-Palop O. Plasma visfatin concentrations increase in both hyper and hypothyroid subjects after normalization of thyroid function and are not related to insulin resistance, anthropometric or inflammatory parameters. Clin Endocrinol (Oxf) 2009; 71: 733-738
  • 12 Ozkaya M, Sahin M, Cakal E, Yuzbasioglu F, Sezer K, Kilinc M, Imrek SS. Visfatin plasma concentrations in patients with hyperthyroidism and hypothyroidism before and after control of thyroid function. J Endocrinol Invest 2009; 32: 435-439
  • 13 Han J, Zhang T, Xiao W, Chang C, Ai H. Up-regulation of visfatin expression in subjects with hyperthyroidism and hypothyroidism is partially relevant to a nonlinear regulation mechanism between visfatin and tri-iodothyronine with various concentrations. Chin Med J 2012; 125: 874-881
  • 14 Salam MHA, Edrees HM. Effect of Different Conditions of Thyroid Function on Serum Adiponectin, Visfatin and Vaspin Levels in Rats. Basic Sci Med 2015; 4: 12-19
  • 15 Yildiz U, Bukan N, Aktas B, Toruner F. Tha relationship between thyroid function and serum levels of angiopoietin-like proetin 3, leptin and visfatin. Acta Endrocrinol Bucharest 2013; 9: 171-179
  • 16 Sawicka-Gutaj N, Zybek-Kocik A, Klimowicz A, Kloska M, Mankowska- Wierzbicka D, Sowinski J, Ruchala M. Circulating Visfatin in Hypothyroidism Is Associated with Free Thyroid Hormones and Antithyroperoxidase Antibodies. Int J Endocrinol 2016; 7402469:
  • 17 Sawicka-Gutaj N, Budny B, Zybek-Kocik A, Sowinski J, Ziemnicka K, Waligorska-Stachura J, Ruchala M. Nicotinamide phosphoribosyltransferase leukocyte overexpression in Graves' opthalmopathy. Endocrine 2016; 53: 497-504
  • 18 Moschen AR, Kaser A, Enrich B, Mosheimer B, Theurl M, Niederegger H, Tilg H. Visfatin, an adipocytokine with proinflammatory and immunomodulating properties. J Immunol 2007; 178: 1748-1758
  • 19 Moschen AR, Geiger S, Gerner R, Tilg H. Pre-B cell colony enhancing factor/NAMPT/visfatin and its role in inflammation-related bone disease. Mutat Res 2010; 690: 95-101
  • 20 Otero M, Lago R, Gomez R, Lago F, Dieguez C, Gomez-Reino J, Gualillo O. Changes in plasma levels of fat-derived hormones adiponectin, leptin, resistin and visfatin in patients with rheumatoid arthritis. Ann Rheum Dis 2006; 65: 1198-1201
  • 21 Ismail S, Mohamed S. Serum levels of visfatin and omentine-1 in patients with psoriasis and their relation to disease severity. Br J Dermatol 2012; 167: 436-439
  • 22 De Sanctis JB, Zabaleta M, Bianco NE, Garmendia JV, Rivas L. Serum adipokine levels in patients with systemic lupus erythematosus: Brief Definite Report. Autoimmunity 2009; 42: 272-274
  • 23 Dahl TB, Yndestad A, Skjelland M, Oie E, Dahl A, Michelsen A, Damas JK, Tunheim SH, Ueland T, Smith C, Bendz B, Tonstad S, Gullestad L, Froland SS, Krohg-Sorensen K, Russell D, Aukrust P, Halvorsen B. Increased expression of visfatin in macrophages of human unstable carotid and coronary atherosclerosis: possible role in inflammation and plaque destabilization. Circulation 2007; 115: 972-980
  • 24 Pearce EN. Patients with Toxic Nodular Goiter and Graves Disease Are at Increased Risk for All-Cause and Cardiovascular Mortality. Clin Thyroidol 2017; 29: 218-220
  • 25 Friebe D, Neef M, Kratzsch J, Erbs S, Dittrich K, Garten A, Petzold-Quinque S, Bluher S, Reinehr T, Stumvoll M, Bluher M, Kiess W, Korner A. Leucocytes are a major source of circulating nicotinamide phosphoribosyltransferase (NAMPT)/pre-B cell colony (PBEF)/visfatin linking obesity and inflammation in humans. Diabetologia 2011; 54: 1200-1211
  • 26 Chomczynski P, Mackey K. Short technical reports. Modification of the TRI reagent procedure for isolation of RNA from polysaccharide- and proteoglycan-rich sources. BioTechniques 1995; 19: 942-945
  • 27 Zahorska-Markiewicz B, Olszanecka-Glinianowicz M, Janowska J, Kocelak P, Semik-Grabarczyk E, Holecki M, Dabrowski P, Skorupa A. Serum concentration of visfatin in obese women. Metabolism 2007; 56: 1131-1134
  • 28 Kovacikova M, Vitkova M, Klimcakova E, Polak J, Hejnova J, Bajzova M, Kovacova Z, Viguerie N, Langin D, Stich V. Visfatin expression in subcutaneous adipose tissue of pre-menopausal women: relation to hormones and weight reduction. Eur J Clin Invest 2008; 38: 516-522
  • 29 Olarescu NC, Ueland T, Lekva T, Dahl TB, Halvorsen B, Aukrust P, Bollerslev J. Adipocytes as a source of increased circulating levels of nicotinamide phosphoribosyltransferase/visfatin in active acromegaly. J Clin Endocrinol Metab 2012; 97: 1355-1362
  • 30 Sorisky A, Gagnon A. Freedom of expression beyond the thyroid: the thyroid-stimulating hormone receptor in the adipocyte. OA Biochemistry 2014; 2: 2
  • 31 Briet C, Suteau-Courant V, Munier M, Rodien P. Thyrotropin receptor, still much to be learned from the patients. Best Practice Res Clin Endocrinol Metab 2018; 32: 155-164
  • 32 Liu R, Hao S, Zhang H, Ma J, Liu X, Xu J, Liu X, Ning J, Sun Y, Jiang L. Correlation of thyroid stimulating hormone receptor mRNA expression levels in peripheral blood with undesirable clinicopathological features in papillary thyroid carcinoma patients. Oncotarget 2017; 8: 74129
  • 33 Brandt F, Thvilum M, Almind D, Christensen K, Green A, Hegedus L, Brix TH. Graves’ disease and toxic nodular goiter are both associated with increased mortality but differ with respect to the cause of death: a Danish population-based register study. Thyroid 2013; 23: 408-413
  • 34 Fadaei R, Parvaz E, Emamgholipour S, Moradi N, Vatannejad A, Najafi M, Doosti M. The mRNA expression and circulating levels of visfatin and their correlation with coronary artery disease severity and 25-hydroxyvitamin D. Horm Metab Res 2016; 48: 269-274
  • 35 Salvi M, Girasole G, Pedrazzoni M, Passeri M, Giuliani N, Minelli R, Braverman LE, Roti E. Increased serum concentrations of interleukin-6 (IL-6) and soluble IL-6 receptor in patients with Graves' disease. J Clin Endocrinol Metab 1996; 81: 2976-2979
  • 36 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. Arthr Rheum 2006; 54: 2084-2095
  • 37 Khalil SF, Mohktar MS, Ibrahim F. The theory and fundamentals of bioimpedance analysis in clinical status monitoring and diagnosis of diseases. Sensors (Basel) 2014; 14: 10895-10928