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