Inflammation

, Volume 31, Issue 5, pp 329–335

Ghrelin and Obestatin Levels in Rheumatoid Arthritis

  • Suleyman Serdar Koca
  • Metin Ozgen
  • Suleyman Aydin
  • Sait Dag
  • Bahri Evren
  • Ahmet Isik
Article

Abstract

Background: Ghrelin is a powerful, endogenous orexigenic peptide. In addition, ghrelin has anti-inflammatory effects, and it has been reported that ghrelin down-regulates pro-inflammatory cytokines, including interleukin (IL)-1β and tumor necrosis factor (TNF)-α. Obestatin appears to decrease food intake and appetite, and its potential role in inflammation is not yet clear. The aims of this study were to assess total and acylated (active) ghrelin and obestatin serum levels and their relations with inflammatory status in rheumatoid arthritis (RA) patients. Design: Fasting blood samples were obtained from 37 patients with RA, 29 patients with Behçet’s disease (BD) and 28 healthy controls (HC). Total ghrelin and obestatin levels were measured by radioimmunoassay and acylated ghrelin was quantified by enzyme-linked immunosorbent assay. Results: Patients with RA had lower total ghrelin, but higher obestatin levels than patients with BD (p < 0.05 for both), but when compared with HC group differences were not significant. There was no difference across groups in terms of acylated ghrelin. Total ghrelin level was not correlated with any study parameters in the all groups. Obestatin level correlated with erythrocyte sedimentation rate and DAS-28 in the RA group, the level of IL-6 in the BD group, and with the level of TNF-α in the HC group (r = 0.400, p < 0.05; r = 0.412, p < 0.05, r = 0.543, p < 0.01 and r = 0.528, p < 0.05, respectively). Conclusions: Our results did not show a significant correlation between circulating ghrelin and clinical or laboratory markers of disease activity in RA. Surprisingly, obestatin correlated with some inflammatory markers. So, obestatin seems to be more valuable than ghrelin in the pathogenesis of RA.

KEY WORDS

ghrelin obestatin rheumatoid arthritis Behçet’s disease 

References

  1. 1.
    Kojima, M., H. Hosoda, Y. Date, M. Nakazato, H. Matsuo, and K. Kangawa. 1999. Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature 402:656–659 doi:10.1038/45230.PubMedCrossRefGoogle Scholar
  2. 2.
    Hosoda, H., M. Kojima, and K. Kangawa. 2006. Biological, physiological, and pharmacological aspects of ghrelin. J. Pharmacol. Sci. 100:398–410 doi:10.1254/jphs.CRJ06002X.PubMedCrossRefGoogle Scholar
  3. 3.
    Leite-Moreira, A. F., and J. B. Soares. 2007. Physiological, pathological and potential therapeutic roles of ghrelin. Drug Discov. Today 12:276–88 doi:10.1016/j.drudis.2007.02.009.PubMedCrossRefGoogle Scholar
  4. 4.
    Zhang, J. V., P. G. Ren, O. Avsian-Kretchmer, C. W. Luo, R. Rauch, C. Klein et al. 2005. Obestatin, a peptide encoded by the ghrelin gene, opposes ghrelin’s effects on food intake. Science 310:996–999 doi:10.1126/science.1117255.PubMedCrossRefGoogle Scholar
  5. 5.
    Sibilia, V., E. Bresciani, N. Lattuada, D. Rapetti, V. Locatelli, V. De Luca et al. 2006. Intracerebroventricular acute and chronic administration of obestatin minimally affect food intake but not weight gain in the rat. J. Endocrinol. Invest. 29:RC31–RC34.PubMedGoogle Scholar
  6. 6.
    Zizzari, P., R. Longchamps, J. Epelbaum, and M. T. Bluet-Pajot. 2007. Obestatin partially affects ghrelin stimulation of food intake and GH secretion in rodents. Endocrinology 148:1648–1653 doi:10.1210/en.2006–1231.PubMedCrossRefGoogle Scholar
  7. 7.
    Dixit, V. D., and D. D. Taub. 2005. Ghrelin and immunity: a young player in an old field. Exp. Gerontol. 40:900–910 doi:10.1016/j.exger.2005.09.003.PubMedCrossRefGoogle Scholar
  8. 8.
    Dixit, V. D., E. M. Schaffer, R. S. Pyle, S. K. Sakthivel, R. Palaniappan Jr., J. W. Lillard et al. 2004. Ghrelin inhibits leptin—and activation-induced proinflammatory cytokine expression by human monocytes and T cells. J Clin Invest. 114:57–66.PubMedGoogle Scholar
  9. 9.
    Granado, M., T. Priego, A. I. Martín, M. A. Villanúa, and A. López-Calderón. 2005. Anti-inflammatory effect of the ghrelin agonist growth hormone-releasing peptide-2 (GHRP-2) in arthritic rats. Am. J. Physiol. Endocrinol. Metab. 288:E486–92 doi:10.1152/ajpendo.00196.2004.PubMedCrossRefGoogle Scholar
  10. 10.
    Peracchi, M., D. Conte, C. Terrani, S. Pizzinelli, C. Gebbia, V. Cappiello et al. 2003. Circulating ghrelin levels in celiac patients. Am. J. Gastroenterol. 98:2474–2478 doi:10.1111/j.1572–0241.2003.07709.x.PubMedCrossRefGoogle Scholar
  11. 11.
    Otero, M., R. Nogueiras, F. Lago, C. Dieguez, J. J. Gomez-Reino, and O. Gualillo. 2004. Chronic inflammation modulates ghrelin levels in humans and rats. Rheumatology (Oxford) 43:306–310 doi:10.1093/rheumatology/keh055.CrossRefGoogle Scholar
  12. 12.
    Toussirot, E., G. Streit, N. U. Nguyen, G. Dumoulin, G. Le Huédé, P. Saas et al. 2007. Adipose tissue, serum adipokines, and ghrelin in patients with ankylosing spondylitis. Metabolism 56:1383–1989 doi:10.1016/j.metabol.2007.05.009.PubMedCrossRefGoogle Scholar
  13. 13.
    Jasin, H. E. 2005. Mechanisms of tissue damage in rheumatoid arthritis. In: Arthritis and allied conditions a textbook of rheumatology, Koopman, and Moreland eds. 15Williams & Wilkins, Philadelphia, pp. 1141–1164.Google Scholar
  14. 14.
    Sakane, T., M. Takeno, N. Suzuki, and G. Inaba. 1999. Behcet’s disease. N. Engl. J. Med. 341:1284–1291 doi:10.1056/NEJM199910213411707.PubMedCrossRefGoogle Scholar
  15. 15.
    Roubenoff, R., R. A. Roubenoff, L. M. Ward, S. M. Holland, and D. B. Hellmann. 1992. Rheumatoid cachexia: depletion of lean body mass in rheumatoid arthritis. Possible association with tumor necrosis factor. J. Rheumatol. 19:1505–1510.PubMedGoogle Scholar
  16. 16.
    Walsmith, J., and R. A. Roubenoff. 2002. Cachexia in rheumatoid arthritis. Int. J. Cardiol. 85:89–99 doi:10.1016/S0167-5273(02)00237-1.PubMedCrossRefGoogle Scholar
  17. 17.
    Arnett, F. C., S. M. Edworthy, D. A. Bloch, D. J. McShane, J. F. Fries, N. S. Cooper et al. 1988. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum. 31:315–24 doi:10.1002/art.1780310302.PubMedCrossRefGoogle Scholar
  18. 18.
    The International Study Group for Behcet’s disease. 1992. Evaluation of diagnostic (‘classification’) criteria in Behcet’s disease—towards internationally agreed criteria. Br. J. Rheumatol. 31:299–308.CrossRefGoogle Scholar
  19. 19.
    Leeb, B. F., I. Andel, J. Sautner, M. Bogdan, A. Maktari, T. Nothnagl et al. 2005. Disease activity measurement of rheumatoid arthritis: Comparison of the simplified disease activity index (SDAI) and the disease activity score including 28 joints (DAS28) in daily routine. Arthritis Rheum. 53:56–60 doi:10.1002/art.20923.PubMedCrossRefGoogle Scholar
  20. 20.
    Yazici, C., K. Kose, M. Calis, M. DemIr, M. Kirnap, and F. Ates. 2004. Increased advanced oxidation protein products in Behcet’s disease: a new activity marker? Br. J. Dermatol. 151:105–11 doi:10.1111/j.1365-2133.2004.06003.x.PubMedCrossRefGoogle Scholar
  21. 21.
    Bekpinar, S., N. Kilic, Y. Unlucerci, A. Akdag-Kose, G. Azizlerli, and Z. Ozbek-Kir. 2005. Evaluation of nitrosative and oxidative stress in Behcet disease. J. Eur. Acad. Dermatol. Venereol. 19:167–71 doi:10.1111/j.1468-3083.2005.01075.x.PubMedCrossRefGoogle Scholar
  22. 22.
    Hosoda, H., and K. Kangawa. 2004. Ghrelin measurement. Nippon Rinsho. 9:354–356.Google Scholar
  23. 23.
    Li, W. G., D. Gavrila, X. Liu, L. Wang, S. Gunnlaugsson, L. L. Stoll et al. 2004. Ghrelin inhibits proinflammatory responses and nuclear factor-kappaB activation in human endothelial cells. Circulation 109:2221–2216 doi:10.1161/01.CIR.0000127956.43874.F2.PubMedCrossRefGoogle Scholar
  24. 24.
    Işerim, S. O., G. Sener, B. Saglam, F. Ercan, N. Gedik, and B. C. Yeğen. 2008. Ghrelin alleviates biliary obstruction-induced chronic hepatic injury in rats. Regul Pept. 146:73–79 doi:10.1016/j.regpep.2007.08.014.CrossRefGoogle Scholar
  25. 25.
    Wang, L., N. R. Basa, A. Shaikh, A. Luckey, D. Heber, D. H. St-Pierre et al. 2006. LPS inhibits fasted plasma ghrelin levels in rats: role of IL-1 and PGs and functional implications. Am. J. Physiol. Gastrointest. Live.r Physiol. 291:G611–G620 doi:10.1152/ajpgi.00533.2005.CrossRefGoogle Scholar
  26. 26.
    Gayle, D. A., M. Desai, E. Casillas, R. Beloosesky, and M. G. Ross. 2006. Gender-specific orexigenic and anorexigenic mechanisms in rats. Life Sci. 79:1531–1536 doi:10.1016/j.lfs.2006.04.015.PubMedCrossRefGoogle Scholar
  27. 27.
    Hataya, Y., T. Akamizu, H. Hosoda, N. Kanamoto, K. Moriyama, K. Kangawa et al. 2003. Alterations of plasma ghrelin levels in rats with lipopolysaccharide-induced wasting syndrome and effects of ghrelin treatment on the syndrome. Endocrinology 144:5365–5371 doi:10.1210/en.2003-0427.PubMedCrossRefGoogle Scholar
  28. 28.
    Chang, L., J. Zhao, J. Yang, Z. Zhang, J. Du, and C. Tang. 2003. Therapeutic effects of ghrelin on endotoxic shock in rats. Eur J Pharmacol. 473:171–176 doi:10.1016/S0014-2999(03)01972-1.PubMedCrossRefGoogle Scholar
  29. 29.
    Kümpers, P., R. Horn, G. Brabant, A. Woywodt, M. Schiffer, H. Haller et al. 2008. Serum leptin and ghrelin correlate with disease activity in ANCA-associated vasculitis. Rheumatology (Oxford) 47:484–487 doi:10.1093/rheumatology/ken023.CrossRefGoogle Scholar
  30. 30.
    Peracchi, M., M. T. Bardella, F. Caprioli, S. Massironi, D. Conte, L. Valenti et al. 2006. Circulating ghrelin levels in patients with inflammatory bowel disease. Gut. 55:432–423 doi:10.1136/gut.2005.079483.PubMedCrossRefGoogle Scholar
  31. 31.
    Otto, B., M. Tschöp, W. Heldwein, A. F. Pfeiffer, and S. Diederich. 2004. Endogenous and exogenous glucocorticoids decrease plasma ghrelin in humans. Eur. J. Endocrinol. 151:113–117 doi:10.1530/eje.0.1510113.PubMedCrossRefGoogle Scholar
  32. 32.
    Madison, L. D., J. M. Scarlett, P. Levasseur, X. Zhu, K. Newcomb, A. Batra et al. 2008. Prostacyclin signaling regulates circulating ghrelin during acute inflammation. J. Endocrinol. 196:263–273 doi:10.1677/JOE-07-0478.PubMedCrossRefGoogle Scholar
  33. 33.
    El Eter, E., A. Al Tuwaijiri, H. Hagar, and M. Arafa. 2007. In vivo and in vitro antioxidant activity of ghrelin: Attenuation of gastric ischemic injury in the rat. J Gastroenterol Hepatol. 22:1791–1799 doi:10.1111/j.1440-1746.2006.04696.x.PubMedCrossRefGoogle Scholar
  34. 34.
    Isik, A., S. S. Koca, B. Ustundag, H. Celik, and A. Yildirim. 2007. Paraoxonase and arylesterase levels in rheumatoid arthritis. Clin. Rheumatol. 26:342–348 doi:10.1007/s10067-006-0300-8.PubMedCrossRefGoogle Scholar
  35. 35.
    Hotta, M., R. Ohwada, H. Katakami, T. Shibasaki, N. Hizuka, and K. Takano. 2004. Plasma levels of intact and degraded ghrelin and their responses to glucose infusion in anorexia nervosa. J. Clin. Endocrino.l Metab. 89:5707–5712 doi:10.1210/jc.2004-0353.CrossRefGoogle Scholar
  36. 36.
    Gourcerol, G., T. Coskun, L. S. Craft, J. P. Mayer, M. L. Heiman, L. Wang et al. 2007. Preproghrelin-derived peptide, obestatin, fails to influence food intake in lean or obese rodents. Obesity (Silver Spring) 15:2643–52.CrossRefGoogle Scholar
  37. 37.
    Gourcerol, G., D. H. St-Pierre, and Y. Taché. 2007. Lack of obestatin effects on food intake: should obestatin be renamed ghrelin-associated peptide (GAP)? Regul Pept. 141:1–7 doi:10.1016/j.regpep.2006.12.023.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Suleyman Serdar Koca
    • 1
  • Metin Ozgen
    • 1
  • Suleyman Aydin
    • 2
  • Sait Dag
    • 1
  • Bahri Evren
    • 1
  • Ahmet Isik
    • 1
  1. 1.Department of Rheumatology, Faculty of MedicineFirat UniversityElazigTurkey
  2. 2.Department of Biochemistry, Faculty of MedicineFirat UniversityElazigTurkey

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