Expression of tumor necrosis factor (TNF)-α protein in the subcutaneous and visceral adipose tissue in correlation with adipocyte cell volume, serum TNF-α, soluble serum TNF-receptor-2 concentrations and C-peptide level

Objective: The aim of the study was to evaluate the expression of tumor necrosis factor (TNF)-alpha protein in the subcutaneous and visceral adipose tissue in correlation with adipocyte cell volume, serum TNF-alpha, soluble TNF-receptor-2 (sTNFR-2) and indirect parameters of insulin resistance in overweight/obese and lean healthy persons. Design: A cross-sectional case-control study was used. Patients: Twenty-eight overweight/obese probands with normal glucose tolerance (BMI > 27 kg/m(2)) and 15 lean people (BMI < 25 kg/m(2)), all of them undergoing planned surgical operation, participated in the study. Methods: Two to four grams of subcutaneous and visceral adipose tissue were removed and studied using semi-quantitative immunohistochemical staining of the TNF-alpha protein. Serum TNF-alpha, sTNFR-2 (ELISA) and fasting C-peptide (RIA) were measured. Results: TNF-alpha protein was expressed in adipocytes of both depots. The expression was evaluated visually and found to be greater in the obese patients. Significantly higher serum TNF-alpha (5.58 +/- 0.87 pg/ml vs 4.21 +/- 0.55, mean +/- S.D., P < 0.01, Mann-Whitney) and sTNFR-2 levels (7.84 +/- 3.56 ng/ml vs 4.59 +/- 1.35, P = 0.005) were found in the obese subgroup in correlation with the fasting C-peptide level (r = 0.49, P = 0.003; and r = 0.74, P = 0.001) and the C-peptide/ blood glucose ratio (r = 0.47, Spearman, P = 0.005; and r = 0.70, P = 0.001). The cell volume of both adipocyte depots was found to have a significant positive correlation with serum TNF-alpha, and sTNFR-2 levels in the total group of patients (subcutaneous: r = 0.52, P = 0.0003; r = 0.69, P < 0.0001; visceral: r = 0.65, P < 0.0001; r = 0.63, P < 0.0001) and in both subgroups. Conclusions: Adipocyte cell volume of both the subcutaneous and visceral fat depots may be determinants of TNF-alpha, sTNFR-2 production and obesity-linked insulin resistance.