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

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 Olga Pivovarova-Ramich and Natalia Rudovich contributed equally to this work.

Increased Serum WISP1 Levels are Associated with Lower Extremity Atherosclerotic Disease in Patients with Type 2 Diabetes Mellitus

“…serum WISP1 levels independently contribute to LEAD in patients with newly diagnosed T2DM. When comparing previously published data from Hörbelt et al [12], Klimontov et al [13], and Tacke et al [17], we reported relatively high levels of WISP1 in our cohort. According to the study of Tacke et al [17], WISP1 levels in serum samples were higher than that in plasma.…”

Hepatic Wnt1 Inducible Signaling Pathway Protein 1 (WISP-1/CCN4) Associates with Markers of Liver Fibrosis in Severe Obesity

“…Further, in the HSC model, exposure to CCN4 caused a dose-dependent induction of fibrosis markers and proinflammatory cytokines alone or in combination with TGF-β treatment. These findings extend our previous studies showing the functions of CCN4 in insulin resistance and inflammation [ 15 , 16 , 17 , 26 ].…”

“…In our previous work, CCN4 mRNA expression in VAT showed a positive correlation with CCL2 expression in a cohort of normal-weight and obese subjects [ 16 ]. In a cohort of subjects with type 2 diabetes, the circulating CCN4 levels correlated positively with fat mass, serum leptin, resistin, and visfatin levels [ 26 ], suggesting that CCN4 may contribute to the metabolically-induced tissue inflammation.…”

An Update to the WISP-1/CCN4 Role in Obesity, Insulin Resistance and Diabetes

“…Several studies investigated the association of WISP-1 and type 2 diabetes mellitus. Klimontov et al demonstrated significantly higher serum levels of WISP-1 in the group of subjects diagnosed with type 2 diabetes mellitus than in healthy controls [ 38 ]. In contrast, a study comparing circulating levels of WISP-1 in the group of men with obesity with and without type 2 diabetes mellitus revealed no significant difference [ 29 ].…”