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 serum TNF-receptor-2 concentrations and C-peptide level

Abstract

Objective: The aim of the study was to evaluate the expression of tumor necrosis factor (TNF)-a protein in the subcutaneous and visceral adipose tissue in correlation with adipocyte cell volume, serum TNFa, 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-a protein. Serum TNF-a, sTNFR-2 (ELISA) and fasting C-peptide (RIA) were measured. Results: TNF-a 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-a (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 ¼ 0.005) were found in the obese subgroup in correlation with the fasting C-peptide level (r ¼ 0.49, P ¼ 0.003; and r ¼ 0.74, P ¼ 0.001) and the C-peptide/ blood glucose ratio (r ¼ 0.47, Spearman, P ¼ 0.005; and r ¼ 0.70, P ¼ 0.001). The cell volume of both adipocyte depots was found to have a significant positive correlation with serum TNF-a and sTNFR-2 levels in the total group of patients (subcutaneous: r ¼ 0.52, P ¼ 0.0003; r ¼ 0.69, P , 0.0001; visceral: r ¼ 0.65, P , 0.0001; r ¼ 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-a, sTNFR-2 production and obesity-linked insulin resistance.

Fat redistribution preferentially reflects the anti-inflammatory benefits of pioglitazone treatment

“…The relation of CRP to abdominal adiposity has been reported to be due to the production of cytokines in adipose tissue, tumor necrosis factor (TNF)-α ,and interleukin (IL)-6. Indeed, the serum concentrations of TNF-α [47][48][49][50] and soluble serum TNFreceptor-2 [49] are higher in obesity; and TNF-α induces hepatic CRP production [51]. Likewise, IL-6 also induces hepatic production of CRP [52]; and serum IL-6 concentrations are higher in obesity [50].…”

Fat poetry: a kingdom for PPARγ

“…Thus, it is the macrophage-produced TNF-α that is responsible for the systemic effects [86]. Although there is no clear correlation between obesity and insulin resistance versus levels of plasma TNF-α, expression of this cytokine in WAT correlates with these two pathologies [87,88]. Chronic exposure of mice to TNF-α induces insulin resistance, decreases the expression of genes involved in adipogenesis and lipogenesis in WAT, and promotes lipolysis, while deletion of the TNF-α gene improves circulating FFA and insulin sensitivity in mouse obesity [89].…”

Abdominal Obesity and Metabolic Alterations in the Menopausal Transition

“…Adipose tissue secretes factors that stimulate the production of inflammatory markers from the liver and other organs, and the adipocytes themselves are the immediate source of most of these inflammatory markers [62]. Visceral adipose tissue from obese patients also has been found to secrete higher levels of PAI-1, IL-6, TNF-α, and leptin and lower levels of adiponectin compared with lean patients [64][65][66]. Circulating inflammatory markers elevated in obese patients include CRP and serum amyloid A (SAA) [67,68].…”