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Circulating Wnt1-inducible signaling pathway protein-1 (WISP-1/CCN4) is a novel biomarker of adiposity in subjects with type 2 diabetes

  • Vadim V. Klimontov
  • Dinara M. Bulumbaeva
  • Olga N. Fazullina
  • Alexander P. Lykov
  • Natalia P. Bgatova
  • Nikolay B. Orlov
  • Vladimir I. Konenkov
  • Andreas F.H. Pfeiffer
  • Olga Pivovarova-RamichEmail author
  • Natalia Rudovich
ORIGINAL ARTICLE
  • 46 Downloads

Abstract

Background

Wnt1-inducible signaling pathway protein 1, or cellular communication network factor 4 (CCN4), a member of CCN family of secreted, extracellular matrix associated signaling proteins, recently was validated as a novel adipose tissue derived cytokine.

Objective

To assess the relationships between circulating CCN4, adipose tissue distribution and function, and chronic low-grade inflammation in subjects with type 2 diabetes.

Methods

We observed 156 patients with type 2 diabetes and 24 healthy controls. Serum levels of CCN4, hsCRP and alpha1-acid glycoprotein (alpha1-AGP) were measured by ELISA. Serum concentrations of leptin, resistin, visfatin, adipsin, adiponectin, IL-6, IL-8, IL-18 and TNF-alpha were determined by multiplex analysis. Fat mass and distribution was assessed by DEXA. Mean diameter of adipocytes was estimated in samples of subcutaneous adipose tissue.

Results

Patients with diabetes had higher levels of circulating CCN4, leptin, resistin, adipsin, visfatin, hsCRP, alpha1-AGP, and IL-6 (all p < 0.02). The CCN4 concentration correlated positively with percentage of fat mass in central abdominal area, as well as with leptin, resistin and visfatin levels; negative correlation was found between CCN4 and mean adipocyte diameter. In multiple regression analysis fat mass in central abdominal area was independent predictor for CCN4 concentration.

Conclusion

In subjects with type 2 diabetes serum levels of CCN4 are associated with central abdominal fat mass and adipose tissue dysfunction.

Keywords

WISP-1/CCN4 Type 2 diabetes Cytokines Obesity Adipose tissue 

Notes

Acknowledgments

This work was financially supported by a grant to N.R. from European Foundation for Study of Diabetes (EFSD/AZ Cellular Plasticity “Unravelling the role of WISP1 on metabolic and cellular plasticity in white adipose tissue”) and by a grant to O. P.-R. from the German Center for Diabetes Research (DZD) (“Role of Wnt-inducible signaling pathway protein-1 (WISP-1) in adipose tissue and liver fibrosis in mice and men”).

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Copyright information

© The International CCN Society 2019

Authors and Affiliations

  • Vadim V. Klimontov
    • 1
  • Dinara M. Bulumbaeva
    • 1
  • Olga N. Fazullina
    • 1
  • Alexander P. Lykov
    • 1
  • Natalia P. Bgatova
    • 1
  • Nikolay B. Orlov
    • 1
  • Vladimir I. Konenkov
    • 1
  • Andreas F.H. Pfeiffer
    • 2
    • 3
    • 4
  • Olga Pivovarova-Ramich
    • 2
    • 3
    • 4
    • 5
    Email author
  • Natalia Rudovich
    • 2
    • 3
    • 6
  1. 1.Research Institute of Clinical and Experimental LymphologyBranch of the Institute of Cytology and GeneticsNovosibirskRussian Federation
  2. 2.Department of Clinical NutritionGerman Institute of Human NutritionNuthetalGermany
  3. 3.Department of Endocrinology, Diabetes and Nutrition, Campus Benjamin FranklinCharité University MedicineBerlinGermany
  4. 4.German Center for Diabetes Research (DZD)NeuherbergGermany
  5. 5.Reseach Group Molecular Nutritional Medicine, Department of Molecular ToxicologyGerman Institute of Human Nutrition Potsdam-RehbrueckeNuthetalGermany
  6. 6.Division of Endocrinology and Diabetes, Department of Internal MedicineSpitalBülachBülachSwitzerland

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