Clinical Rheumatology

, Volume 35, Issue 6, pp 1535–1540 | Cite as

Serum adropin level and ENHO gene expression in systemic sclerosis

  • Servet Yolbas
  • Murat Kara
  • Musa Yilmaz
  • Suleyman Aydin
  • Suleyman Serdar KocaEmail author
Original Article


Adropin, a secreted protein, is encoded by the energy homeostasis associated (ENHO) gene. It has been implicated in the several physiological and pathological processes such as angiogenesis and apoptosis. Therefore, the aim of present study was to investigate serum adropin levels and ENHO gene expressions in systemic sclerosis (SSc) characterized by vasculopathy, inflammation, and progressive fibrosis of the skin and internal organs. The study includes 27 patients with SSc, 39 patients with Behçet’s disease (BD), and 20 healthy controls (HC). Serum adropin levels and ENHO gene expressions by peripheral blood mononuclear cells were analyzed by ELISA method and by real-time PCR, respectively. The serum adropin levels were higher in the SSc and BD groups than in the HC group (p = 0.023 and p < 0.001, respectively). However, there were no significant differences among the groups in terms of ENHO gene expressions (p ANOVA = 0.149). There was no significant difference between the limited and diffuse cutaneous subtypes of SSc in terms of serum adropin level and ENHO gene expression. Moreover, serum adropin level and ENHO gene expression were not associated with the disease activity and severity indexes. ENHO gene expression was correlated with the triglyceride levels in the BD group (r = −0.426, p = 0.027). The augmented serum adropin levels may be expected in the chronic inflammatory disease and seem not to be characteristic of only SSc. However, further studies are needed to explain the precise role of adropin in SSc.


Adropin Behçet’s disease ENHO Systemic sclerosis 


Compliance with ethical standards

The protocol of this study was approved by the institutional ethics committee, and all the participants gave informed consent before enrolling in the study.




  1. 1.
    Ho YY, Lagares D, Tager AM, Kapoor M (2014) Fibrosis—a lethal component of systemic sclerosis. Nat Rev Rheumatol 10(7):390–402CrossRefPubMedGoogle Scholar
  2. 2.
    Denton CP, Black CM (2004) Scleroderma—clinical and pathological advances. Best Pract Res Clin Rheumatol 18:271–290CrossRefPubMedGoogle Scholar
  3. 3.
    Trojanowska M (2010) Cellular and molecular aspects of vascular dysfunction in systemic sclerosis. Nat Rev Rheumatol 6:453–460CrossRefPubMedGoogle Scholar
  4. 4.
    Kumar KG, Trevaskis JL, Lam DD et al (2008) Identification of adropin as a secreted factor linking dietary macronutrient intake with energy homeostasis and lipid metabolism. Cell Metab 8:468–481CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Lovren F, Pan Y, Quan A, Singh KK, Shukla PC, Gupta M, Al-Omran M, Teoh H, Verma S (2010) Adropin is a novel regulator of endothelial function. Circulation 122:185–192CrossRefGoogle Scholar
  6. 6.
    Aydin S, Kuloglu T, Aydin S, Eren MN, Yilmaz M, Kalayci M, Sahin I, Kocaman N, Citil C, Kendir Y (2013) Expression of adropin in rat brain, cerebellum, kidneys, heart, liver, and pancreas in streptozotocin-induced diabetes. Mol Cell Biochem 380:73–81CrossRefPubMedGoogle Scholar
  7. 7.
    van den Hoogen F, Khanna D, Fransen J et al (2013) 2013 classification criteria for systemic sclerosis: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Ann Rheum Dis 72:1747–1755CrossRefPubMedGoogle Scholar
  8. 8.
    International Study Group for Behçet’s Disease (1990) Criteria for diagnosis of Behçet’s disease. Lancet 335:1078–1080Google Scholar
  9. 9.
    Valentini G, Della Rossa A, Bombardieri S et al (2001) European multicentre study to define disease activity criteria for systemic sclerosis. II. Identification of disease activity variables and development of preliminary activity indexes. Ann Rheum Dis 60:592–598CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Medsger TA Jr, Silman AJ, Steen VD et al (1999) A disease severity scale for systemic sclerosis: development and testing. J Rheumatol 26:2159–2167PubMedGoogle Scholar
  11. 11.
    Clements P, Lachenbruch P, Siebold J et al (1995) Inter and intraobserver variability of total skin thickness score (modified Rodnan TSS) in systemic sclerosis. J Rheumatol 22:1281–1285PubMedGoogle Scholar
  12. 12.
    Isik A, Koca SS, Ustundag B, Selek S (2007) Decreased total antioxidant response and increased oxidative stress in Behcet’s disease. Tohoku J Exp Med 212:133–141CrossRefPubMedGoogle Scholar
  13. 13.
    Yilmaz S, Simsek I, Cinar M, Erdem H, Kose O, Yazici Y, Pay S (2013) Patient-driven assessment of disease activity in Behçet’s syndrome: cross-cultural adaptation, reliability and validity of the Turkish version of the Behçet’s syndrome activity score. Clin Exp Rheumatol 31:77–83PubMedGoogle Scholar
  14. 14.
    Wei J, Zhu H, Komura K et al (2014) A synthetic PPAR-γ agonist triterpenoid ameliorates experimental fibrosis: PPAR-γ-independent suppression of fibrotic responses. Ann Rheum Dis 73:446–454CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Pehlivan Y, Onat AM, Ceylan N, Turkbeyler IH, Buyukhatipoglu H, Comez G, Babacan T, Tarakcioglu M (2012) Serum leptin, resistin and TNF-a levels in patients with systemic sclerosis: the role of adipokines in scleroderma. Int J Rheum Dis 15:374–379CrossRefPubMedGoogle Scholar
  16. 16.
    Lakota K, Wei J, Carns M, Hinchcliff M, Lee J, Whitfield ML, Sodin-Semrl S, Varga J (2012) Levels of adiponectin, a marker for PPAR-gamma activity, correlate with skin fibrosis in systemic sclerosis: potential utility as biomarker. Arthritis Res Ther 14:R102CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Lian W, Gu X, Qin Y, Zheng X (2011) Elevated plasma levels of adropin in heart failure patients. Intern Med 50:1523–1527CrossRefPubMedGoogle Scholar
  18. 18.
    Celik A, Balin M, Kobat MA, Erdem K, Baydas A, Bulut M, Altas Y, Aydin S, Aydin S (2013) Deficiency of a new protein associated with cardiac syndrome X; called adropin. Cardiovasc Ther 31:174–178CrossRefPubMedGoogle Scholar
  19. 19.
    Topuz M, Celik A, Aslantas T, Demir AK, Aydin S, Aydin S (2013) Mellitus plasma adropin levels predict endothelial dysfunction like flow-mediated dilatation in patients with type 2 diabetes. J Investig Med 61:1161–1164CrossRefPubMedGoogle Scholar
  20. 20.
    Gozal D, Kheirandish-Gozal L, Bhattacharjee R, Molero-Ramirez H, Tan HL, Bandla HP (2013) Circulating adropin concentrations in pediatric obstructive sleep apnea: potential relevance to endothelial function. J Pediatr 163:1122–1126CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Ganesh Kumar K, Zhang J, Gao S, Rossi J, McGuinness OP, Halem HH, Culler MD, Mynatt RL, Butler AA (2012) Adropin deficiency is associated with increased adiposity and insulin resistance. Obesity 20:1394–1402CrossRefPubMedGoogle Scholar
  22. 22.
    Kershaw EE, Flier JS (2004) Adipose tissue as an endocrine organ. J Clin Endocrinol Metab 89:2548–2556CrossRefPubMedGoogle Scholar
  23. 23.
    Pelleymounter MA, Cullen MJ, Baker MB, Hecht R, Winters D, Boone T, Collins F (1995) Effects of the obese gene product on body weight regulation in ob/ob mice. Science 269:540–543CrossRefPubMedGoogle Scholar
  24. 24.
    Halaas JL, Gajiwala KS, Maffei M, Cohen SL, Chait BT, Rabinowitz D, Lallone RL, Burley SK, Friedman JM (1995) Weight-reducing effects of the plasma protein encoded by the obese gene. Science 269:543–546CrossRefPubMedGoogle Scholar
  25. 25.
    Evereklioglu C, Inalöz HS, Kirtak N, Doganay S, Bülbül M, Ozerol E, Er H, Ozbek E (2002) Serum leptin concentration is increased in patients with Behçet’s syndrome and is correlated with disease activity. Br J Dermatol 147:331–336CrossRefPubMedGoogle Scholar
  26. 26.
    Marighela TF, Genaro Pde S, Pinheiro MM, Szejnfeld VL, Kayser C (2013) Risk factors for body composition abnormalities in systemic sclerosis. Clin Rheumatol 32:1037–1044CrossRefPubMedGoogle Scholar
  27. 27.
    Baron M, Hudson M, Steele R, Canadian Scleroderma Research Group (2009) Malnutrition is common in systemic sclerosis: results from the Canadian Scleroderma Research Group database. J Rheumatol 36:2737–2743CrossRefPubMedGoogle Scholar
  28. 28.
    Kuhla A, Hahn S, Butschkau A, Lange S, Wree A, Vollmar B (2014) Lifelong caloric restriction reprograms hepatic fat metabolism in mice. J Gerontol A Biol Sci Med Sci 69:915–922CrossRefPubMedGoogle Scholar
  29. 29.
    Abraham DJ, Krieg T, Distler J, Distler O (2009) Overview of pathogenesis of systemic sclerosis. Rheumatology 48:iii3–iii7CrossRefPubMedGoogle Scholar
  30. 30.
    Liakouli V, Cipriani P, Marrelli A, Alvaro S, Ruscitti P, Giacomelli R (2011) Angiogenic cytokines and growth factors in systemic sclerosis. Autoimmun Rev 10:590–594CrossRefPubMedGoogle Scholar

Copyright information

© International League of Associations for Rheumatology (ILAR) 2016

Authors and Affiliations

  • Servet Yolbas
    • 1
  • Murat Kara
    • 2
  • Musa Yilmaz
    • 3
  • Suleyman Aydin
    • 3
  • Suleyman Serdar Koca
    • 1
    Email author
  1. 1.Department of Rheumatology, Faculty of MedicineFirat UniversityElazigTurkey
  2. 2.Department of Medical Genetics, Faculty of MedicineMugla Sitki Kocman UniversityMuglaTurkey
  3. 3.Department of Biochemistry, Faculty of MedicineFirat UniversityElazigTurkey

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