Associations between plasma nesfatin-1 levels and the presence and severity of coronary artery disease

  • Susumu Ibe
  • Yoshimi Kishimoto
  • Hanako Niki
  • Emi Saita
  • Tomohiko Umei
  • Kotaro Miura
  • Yukinori Ikegami
  • Reiko Ohmori
  • Kazuo Kondo
  • Yukihiko MomiyamaEmail author
Original Article


Nesfatin-1 is a recently identified anorexigenic peptide mainly secreted from the brain and adipose tissue. Although nesfatin-1 may have pro-inflammatory and apoptotic properties, the association between plasma nesfatin-1 levels and coronary artery disease (CAD) has not been clarified yet. We investigated plasma nesfatin-1 levels in 302 patients undergoing elective coronary angiography. Of the 302 study patients, CAD was present in 172 (57%), of whom 67 had 1-vessel, 49 had 2-vessel, and 56 had 3-vessel disease. Compared with 130 patients without CAD, 172 with CAD had higher plasma nesfatin-1 levels (median 0.21 vs. 0.17 ng/mL, P < 0.01). A stepwise increase in nesfatin-1 levels was found depending on the number of > 50% stenotic coronary vessels: 0.17 in CAD(−), 0.20 in 1-vessel, 0.21 in 2-vessel, and 0.22 ng/mL in 3-vessel disease (P < 0.05). A high nesfatin-1 level (> 0.19 ng/mL) was found in 43% of patients with CAD(−), 55% of those with 1-vessel, 55% of those with 2-vessel, and 68% of those with 3-vessel disease (P < 0.05). Nesfatin-1 levels significantly correlated with the number of > 50% stenotic coronary segments (r = 0.14, P < 0.02). In multivariate analysis, plasma nesfatin-1 levels were a significant factor for CAD independent of atherosclerotic risk factors. The odds ratio for CAD was 1.71 (95% CI 1.01–2.91) for high nesfatin-1 level of > 0.19 ng/mL (P < 0.05). Thus, plasma nesfatin-1 levels were found to be high in patients with CAD and were associated with CAD independent of atherosclerotic risk factors, suggesting that high nesfatin-1 levels in patients with CAD may play a role in the development of coronary atherosclerosis.


Atherosclerosis Biomarker Coronary artery disease Nesfatin-1 



This study was supported in part by a grant from Honjo International Scholarship Foundation. Financial funding was also provided in part by Bayer Yakuhin Ltd. and Pfizer Japan Inc.; however, these sponsors had no role in the design, analysis, or interpretation of our study.

Compliance with ethical standards

Conflict of interest

Our study has no conflicts of interest to disclose.


  1. 1.
    Oh-I S, Shimizu H, Satoh T, Okada S, Adachi S, Inoue K, Eguchi H, Yamamoto M, Imaki T, Hashimoto K, Tsuchiya T, Monden T, Horiguchi K, Yamada M, Mori M (2006) Identification of nesfatin-1 as a satiety molecule in the hypothalamus. Nature 443(7112):709–712CrossRefGoogle Scholar
  2. 2.
    Ramanjaneya M, Chen J, Brown JE, Tripathi G, Hallschmid M, Patel S, Kern W, Hillhouse EW, Lehnert H, Tan BK, Randeva HS (2010) Identification of nesfatin-1 in human and murine adipose tissue: a novel depot-specific adipokine with increased levels in obesity. Endocrinology 151(7):3169–3180CrossRefGoogle Scholar
  3. 3.
    Yosten GL, Samson WK (2009) Nesfatin-1 exerts cardiovascular actions in brain: possible interaction with the central melanocortin system. Am J Physiol Regul Integr Comp Physiol 297(2):R330–R336CrossRefGoogle Scholar
  4. 4.
    Su Y, Zhang J, Tang Y, Bi F, Liu JN (2010) The novel function of nesfatin-1: anti-hyperglycemia. Biochem Biophys Res Commun 391(1):1039–1042CrossRefGoogle Scholar
  5. 5.
    Zhang Z, Li L, Yang M, Liu H, Boden G, Yang G (2012) Increased plasma levels of nesfatin-1 in patients with newly diagnosed type 2 diabetes mellitus. Exp Clin Endocrinol Diabetes 120(2):91–95CrossRefGoogle Scholar
  6. 6.
    Algul S, Ozkan Y, Ozcelik O (2016) Serum nesfatin-1 levels in patients with different glucose tolerance levels. Physiol Res 65(6):979–985Google Scholar
  7. 7.
    Li QC, Wang HY, Chen X, Guan HZ, Jiang ZY (2010) Fasting plasma levels of nesfatin-1 in patients with type 1 and type 2 diabetes mellitus and the nutrient-related fluctuation of nesfatin-1 level in normal humans. Regul Pept 159(1–3):72–77CrossRefGoogle Scholar
  8. 8.
    Özsavcí D, Erşahin M, Şener A, Özakpinar ÖB, Toklu HZ, Akakín D, Şener G, Yeğen BÇ (2011) The novel function of nesfatin-1 as an anti-inflammatory and antiapoptotic peptide in subarachnoid hemorrhage-induced oxidative brain damage in rats. Neurosurgery 68(6):1699–1708CrossRefGoogle Scholar
  9. 9.
    Tang CH, Fu XJ, Xu XL, Wei XJ, Pan HS (2012) The anti-inflammatory and anti-apoptotic effects of nesfatin-1 in the traumatic rat brain. Peptides 36(1):39–45CrossRefGoogle Scholar
  10. 10.
    Scotece M, Conde J, Abella V, López V, Lago F, Pino J, Gómez-Reino JJ, Gualillo O (2014) NUCB2/nesfatin-1: a new adipokine expressed in human and murine chondrocytes with pro-inflammatory properties, an in vitro study. J Orthop Res 32(5):653–660CrossRefGoogle Scholar
  11. 11.
    Ramanjaneya M, Tan BK, Rucinski M, Kawan M, Hu J, Kaur J, Patel VH, Malendowicz LK, Komarowska H, Lehnert H, Randeva HS (2015) Nesfatin-1 inhibits proliferation and enhances apoptosis of human adrenocortical H295R cells. J Endocrinol 226(1):1–11CrossRefGoogle Scholar
  12. 12.
    Jiang L, Bao J, Zhou X, Xiong Y, Wu L (2013) Increased serum levels and chondrocyte expression of nesfatin-1 in patients with osteoarthritis and its relation with BMI, hsCRP, and IL-18. Mediat Inflamm 2013:631251Google Scholar
  13. 13.
    Leivo-Korpela S, Lehtimäki L, Hämälainen M, Vuolteenaho K, Kööbi L, Järvenpää R, Kankaanranta H, Saarelainen S, Moilanen E (2014) Adipokines NUCB2/nesfatin-1 and visfatin as novel inflammatory factors in chronic obstructive pulmonary disease. Mediat Inflamm 2014:232167CrossRefGoogle Scholar
  14. 14.
    Xia QR, Liang J, Cao Y, Shan F, Liu Y, Xu Y (2018) Increased plasma nesfatin-1 levels may be associated with corticosterone, IL-6, and CRP levels in patients with major depressive disorder. Clin Chim Acta 480:107–111CrossRefGoogle Scholar
  15. 15.
    Dai H, Li X, He T, Wang Y, Wang Z, Wang S, Xing M, Sun W, Ding H (2013) Decreased plasma nesfatin-1 levels in patients with acute myocardial infarction. Peptides 46:167–171CrossRefGoogle Scholar
  16. 16.
    Sahin FK, Sahin SB, Ural UM, Cure MC, Senturk S, Tekin YB, Balik G, Cure E, Yuce S, Kirbas A (2015) Nesfatin-1 and vitamin D levels may be associated with systolic and diastolic blood pressure value and hearth rate in polycystic ovary syndrome. Bosn J Basic Med Sci 15(3):57–63Google Scholar
  17. 17.
    Zhang JR, Lu QB, Feng WB, Wang HP, Tang ZH, Cheng H, Du Q, Wang YB, Li KX, Sun HJ (2018) Nesfatin-1 promotes VSMC migration and neointimal hyperplasia by upregulating matrix metalloproteinases and downregulating PPARγ. Biomed Pharmacother 102:711–717CrossRefGoogle Scholar
  18. 18.
    Lu QB, Wand HP, Tang ZH, Cheng H, Du Q, Wang YB, Feng WB, Li KX, Cai WW, Qiu LY, Sun HJ (2018) Nesfatin-1 functions as a switch for phenotype transformation and proliferation of VSMCs in hypertensive vascular remodeling. Biochim Biophys Acta 1864 1864(6 Pt A):2154–2168Google Scholar
  19. 19.
    Yamawaki H, Takahashi M, Mukohda M, Morita T, Okada M, Hara Y (2012) A novel adipocytokine, nesfatin-1 modulates peripheral arterial contractility and blood pressure in rats. Biochem Biophys Res Commun 418(4):676–681CrossRefGoogle Scholar
  20. 20.
    Xu YY, Ge JF, Qin G, Peng YN, Zhang CF, Liu XR, Liang LC, Wang ZZ, Chen FH, Li J (2015) Acute, but not chronic, stress increased the plasma concentration and hypothalamic mRNA expression of NUCB2/nesfatin-1 in rats. Neuropeptides 54:47–53CrossRefGoogle Scholar
  21. 21.
    Robinson C, Tsang L, Solomon A, Woodiwiss AJ, Gunter S, Mer M, Hsu HC, Gomes M, Norton GR, Millen AME, Dessein PH (2018) Nesfatin-1 and visfatin expression is associated with reduced atherosclerotic disease risk in patients with rheumatoid arthritis. Peptides 102:31–37CrossRefGoogle Scholar
  22. 22.
    Zhai T, Li SZ, Fan XT, Tian Z, Lu XQ, Dong J (2017) Circulating nesfatin-1 levels and type 2 diabetes: a systematic review and meta-analysis. J Diabetes Res 2017:7687098CrossRefGoogle Scholar
  23. 23.
    Tsuchiya T, Shimizu H, Yamada M, Osaki A, Oh-I S, Ariyama Y, Takahashi H, Okada S, Hashimoto K, Satoh T, Kojima M, Mori M (2010) Fasting concentrations of nesfatin-1 are negatively correlated with body mass index in non-obese males. Clin Endocrinol 73(4):484–490Google Scholar

Copyright information

© Springer Japan KK, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of CardiologyNational Hospital Organization Tokyo Medical CenterTokyoJapan
  2. 2.Endowed Research Department “Food for Health”Ochanomizu UniversityTokyoJapan
  3. 3.Faculty of Regional DesignUtsunomiya UniversityTochigiJapan
  4. 4.Institute of Life Innovation StudiesToyo UniversityGunmaJapan

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