Current Medical Science

, Volume 38, Issue 5, pp 868–874 | Cite as

Characterization of Wnt1-inducible Signaling Pathway Protein-1 in Obese Children and Adolescents

  • An-ru Wang
  • Xue-qin Yan
  • Cai Zhang
  • Cai-qi Du
  • Wen-jun Long
  • Di Zhan
  • Jie Ren
  • Xiao-ping Luo


Wnt1-inducible signaling pathway protein-1 (WISP1), a member of the CCN family, is increasingly being recognized as a potential target for obesity and type 2 diabetes mellitus. Recent studies have shown that WISP1 can regulate low-grade inflammation in obese mice, and circulating WISP1 levels are associated with obesity and type 2 diabetes mellitus in adults. Herein, we measured serum WISP1 levels in obese youth and explored its relationships with pro-inflammatory cytokine interleukin 18 (IL-18) and other metabolic indexes. Totally, 44 normal-weight and 44 obese children and adolescents were enrolled. Physical and laboratory data were recorded, and then serum levels of WISP1 and IL-18 were determined by enzyme-linked immunosorbent assays. Results showed that serum levels of WISP1 were significantly higher in obese children and adolescents than in normal-weight healthy controls (1735.44±15.29 vs. 1364.08±18.69 pg/mL). WISP1 levels were significantly positively correlated with body mass index (BMI) and BMI z-score (r=0.392, P=0.008; r=0.474, P=0.001, respectively) in obese group; circulating IL-18 was increased in obese individuals (1229.06±29.42 vs. 295.87±13.30 pg/mL). Circulating WISP1 levels were significantly correlated with IL-18 (r=0.542, P<0.001), adiponectin (r=0.585, P<0.001) and leptin (r=0.592, P<0.001). The multivariate stepwise regression analysis showed that higher IL-18 levels represented the main determinant of increased WISP1 levels after adjusting for BMI, waist circumference, fasting insulin, homeostatic model assessment of insulin resistance (HOMA-IR) and HbA1c in obese individuals (β=0.542, P=0.000). WISP1 can be involved in glucose/lipid metabolism in obese youth, which may be modulated by IL-18. Increased WISP1 levels may be a risk factor of obesity and insulin resistance, and WISP1 has a potential therapeutic effect on insulin resistance in obese children and adolescents.

Key words

Wnt1-inducible signaling pathway protein-1 interleukin 18 children and adolescents insulin resistance obesity 


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  1. 1.
    NCD Risk Factor Collaboration (NCD-RisC). World trends in body-mass index, underweight, overweight, and obesity from 1975 to 2016: a pooled analysis of 2416 population-based measured studies in 1289 million children, adolescents, and adults. Lancet, 2017,390(10113):2627–2642CrossRefGoogle Scholar
  2. 2.
    Kaplanski G. Interleukin-18: biological properties and role in disease pathogenesis. Immunol Rev, 2018,281(1):138–153CrossRefGoogle Scholar
  3. 3.
    Maiese K. Programming apoptosis and autophagy with novel approaches for diabetes mellitus. Curr Neurovasc Res, 2015,12(2):173–188CrossRefGoogle Scholar
  4. 4.
    Blüher M, Pfeiffer AF, Rudovich N. WISP1 is a novel adipokine linked to inflammation in obesity. Diabetes, 2015,64(3):856–866CrossRefGoogle Scholar
  5. 5.
    Barchetta I, Cimini FA, Capoccia D, et al. WISP1 is a marker of systemic and adipose tissue inflammation in dysmetabolic subjects with or without type 2 diabetes. J Endocr Soc, 2017,1(6):660–670CrossRefGoogle Scholar
  6. 6.
    Tacke C, Aleksandrova K, Rehfeldt M, et al. Assessment of circulating Wnt1 inducible signalling pathway protein 1 (WISP1)/CCN4 as a novel biomarker of obesity. J Cell Commun Signal, 2018,12(3):539–548CrossRefGoogle Scholar
  7. 7.
    Sahin Ersoy G, AltunEnsari T, Subas S, et al. WISP1 is a novel adipokine linked to metabolic parameters in gestational diabetes mellitus. J Matern Fetal Neonatal Med, 2017,30(8):942–946CrossRefGoogle Scholar
  8. 8.
    Bruun JM, Stallknecht B, Helge JW, et al. Interleukin-18 in plasma and adipose tissue: effects of obesity, insulin resistance, and weight loss. Eur J Endocrinol, 2007,157(4):465–471CrossRefGoogle Scholar
  9. 9.
    Zaharieva E, Kamenov Z, Velikova T, et al. Interleukin-18 serum level is elevated in type 2 diabetes and latent autoimmune diabetes. Endocr Connect, 2018,7(1):179–185CrossRefGoogle Scholar
  10. 10.
    Reddy VS, Valente AJ, Delafontaine P, et al. Interleukin-18/WNT1-inducible signaling pathway protein-1 signaling mediates human saphenous vein smooth muscle cell proliferation. J Cell Physiol, 2011,226(12):3303–3315CrossRefGoogle Scholar
  11. 11.
    Barlow SE, Dietz WH. Obesity evaluation and treatment: Expert Committee recommendations. the maternal and child health bureau, health resources and services administration and department of health and human services. Pediatrics, 1998,102(3):E29CrossRefGoogle Scholar
  12. 12.
    Li H, Ji CY, Zong XN, et al. Body mass index growth curves for Chinese children and adolescents aged 0 to 18 years. Zhonghua Er Ke Za Zhi (Chinese), 2009,47(7):493–498Google Scholar
  13. 13.
    Brown RJ, Yanovski JA. Estimation of insulin sensitivity in children: methods, measures and controversies. Pediatr Diabetes, 2014,15(3):151–161CrossRefGoogle Scholar
  14. 14.
    Wallace TM, Levy JC, Matthews DR. Use and abuse of HOMA modeling. Diabetes Care, 2004,27(6):1487–1495.CrossRefGoogle Scholar
  15. 15.
    Song P, Yu J, Chang X, et al. Prevalence and correlates of metabolic syndrome in Chinese children: the China health and nutrition survey. Nutrients, 2017,9(1). pii: E79CrossRefGoogle Scholar
  16. 16.
    Wu S, Gao H, Ma Y, et al. Characterisation of betatrophin concentrations in childhood and adolescent obesity and insulin resistance. Pediatr Diabetes, 2016,17(1):53–60CrossRefGoogle Scholar
  17. 17.
    Brigstock DR. The CCN family: a new stimulus package. J Endocrinol, 2003,178(2):169–175CrossRefGoogle Scholar
  18. 18.
    Pennica D, Swanson TA, Welsh JW, et al. WISP genes are members of the connective tissue growth factor family that are up-regulated in Wnt-1-transformed cells and aberrantly expressed in human colon tumors. Proc Natl Acad Sci USA, 1998,95(25):14717–14722CrossRefGoogle Scholar
  19. 19.
    Sahin Ersoy G, Altun Ensari T, Vatansever D, et al. Novel adipokines WISP1 and betatrophin in PCOS: relationship to AMH levels, atherogenic and metabolic profile. Gynecol Endocrinol, 2017,33(2):119–123CrossRefGoogle Scholar
  20. 20.
    Okamura H, Tsutsi H, Komatsu T, et al. Cloning of a new cytokine that induces IFN-gamma production by T cells. Nature, 1995,378(6552):88–91CrossRefGoogle Scholar
  21. 21.
    Skurk T, Kolb H, Müller-Scholze S, et al. The proatherogenic cytokine interleukin-18 is secreted by human adipocytes. Eur J Endocrinol, 2005, 152(6):863–868CrossRefGoogle Scholar
  22. 22.
    García VE, Uyemura K, Sieling PA, et al. IL-18 promotes type 1 cytokine production from NK cells and T cells in human intracellular infection. J Immunol, 1999,162(10):6114–6121Google Scholar
  23. 23.
    Presta I, Andreozzi F, Succurro E, et al. IL-18 gene polymorphism and metabolic syndrome. Nutr Metab Cardiovasc Dis, 2009,19(2):e5–6CrossRefGoogle Scholar

Copyright information

© Huazhong University of Science and Technology 2018

Authors and Affiliations

  • An-ru Wang
    • 1
    • 2
  • Xue-qin Yan
    • 3
  • Cai Zhang
    • 1
  • Cai-qi Du
    • 1
  • Wen-jun Long
    • 1
  • Di Zhan
    • 1
  • Jie Ren
    • 1
  • Xiao-ping Luo
    • 1
  1. 1.Department of Pediatrics, Tongji Hospital, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
  2. 2.Department of Pediatricsthe Second Affiliated Hospital of Nanjing Medical UniversityNanjingChina
  3. 3.Department of PediatricsBoai Hospital of ZhongshanZhongshanChina

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