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.

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.

[1]  C. Montague,et al.  Adipose depot‐specific effects of PPARγ agonists: a consequence of differential expression of PPARγ in adipose tissue depots? , 2002 .

[2]  G. Winkler,et al.  Tumor necrosis factor system in insulin resistance in gestational diabetes. , 2002, Diabetes research and clinical practice.

[3]  J. Kobayashi,et al.  Alterations of insulin sensitivity by the implantation of 3T3-L1 cells in nude mice. A role for TNF-α? , 2002, Diabetologia.

[4]  C. Montague.  Adipose depot-specific effects of PPAR gamma agonists: a consequence of differential expression of PPAR gamma in adipose tissue depots? , 2002, Diabetes, obesity & metabolism.

[5]  G. Frühbeck,et al.  The adipocyte: a model for integration of endocrine and metabolic signaling in energy metabolism regulation. , 2001, American journal of physiology. Endocrinology and metabolism.

[6]  A. Hamsten,et al.  Tumour necrosis factor-α (TNF-α) polymorphisms –857C/A and –863C/A are associated with TNF-α secretion from human adipose tissue , 2001, Diabetologia.

[7]  A Tremblay,et al.  Hyperleptinemia is more closely associated with adipose cell hypertrophy than with adipose tissue hyperplasia , 2000, International Journal of Obesity.

[8]  S. Coppack,et al.  Production of soluble tumor necrosis factor receptors by human subcutaneous adipose tissue in vivo. , 1999, American journal of physiology. Endocrinology and metabolism.

[9]  C. Tsigos,et al.  Circulating tumor necrosis factor alpha concentrations are higher in abdominal versus peripheral obesity. , 1999, Metabolism: clinical and experimental.

[10]  H. Hauner,et al.  Expression pattern of tumour necrosis factor receptors in subcutaneous and omental human adipose tissue: role of obesity and non‐insulin‐dependent diabetes mellitus , 1999, European journal of clinical investigation.

[11]  G. Winkler,et al.  Elevated serum TNF‐α level as a link between endothelial dysfunction and insulin resistance in normotensive obese patients , 1999, Diabetic medicine : a journal of the British Diabetic Association.

[12]  M. Pagliassotti,et al.  Adipose tissue-derived tumor necrosis factor activity correlates with fat cell size but not insulin action in aging rats. , 1998, Endocrinology.

[13]  S. O’Rahilly,et al.  Depot-related gene expression in human subcutaneous and omental adipocytes. , 1998, Diabetes.

[14]  H. Hauner,et al.  Tumor necrosis factor-alpha acutely inhibits insulin signaling in human adipocytes: implication of the p80 tumor necrosis factor receptor. , 1998, Diabetes.

[15]  A. Greenberg,et al.  Journal of Clinical Endocrinology and Metabolism Printed in U.S.A. Copyright © 1998 by The Endocrine Society Omental and Subcutaneous Adipose Tissues of Obese Subjects Release Interleukin-6: Depot Difference and Regulation by Glucocorticoid* , 1997 .

[16]  Johan Auwerx,et al.  Depot-Specific Differences in Adipose Tissue Gene Expression in Lean and Obese Subjects , 1998, Diabetes.

[17]  B. Spiegelman,et al.  Differential Regulation of the p80 Tumor Necrosis Factor Receptor in Human Obesity and Insulin Resistance , 1997, Diabetes.

[18]  B. Spiegelman,et al.  Tumor Necrosis Factor (TNF)-α Inhibits Insulin Signaling through Stimulation of the p55 TNF Receptor and Activation of Sphingomyelinase* , 1996, The Journal of Biological Chemistry.

[19]  B. Spiegelman,et al.  Increased adipose tissue expression of tumor necrosis factor-alpha in human obesity and insulin resistance. , 1995, The Journal of clinical investigation.

[20]  B. Spiegelman,et al.  Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. , 1993, Science.

[21]  Z. Sápi,et al.  Fine needle aspiration cytology of biphasic synovial sarcoma of soft tissue. Report of a case with ultrastructural, immunohistologic and cytophotometric studies. , 1990, Acta cytologica.