Secretion of tumor necrosis factor-α shows a strong relationship to insulin-stimulated glucose transport in human adipose tissue

Abstract

Some animal models suggest that tumor necrosis factor (TNF)-α is a key component in obesity-linked insulin resistance because it inhibits insulin receptor signaling and glucose transport in insulin-sensitive tissues. However, in vivo data in humans have given conflicting results regarding the relationship between circulating TNF-α levels and insulin sensitivity. In the present study, the potential local role of TNF-α on insulin action in human subcutaneous adipose tissue was studied in 42 obese women (BMI 39 ± 10 kg/m2). We found a strong inverse correlation between adipose TNF-α secretion and maximum insulin-stimulated glucose transport in adipocytes that was independent of fat cell volume, age, and BMI (P < 0.001, r = 0.58). As much as one-third of the variation in insulin-stimulated glucose transport could be accounted for by variations in TNF-α secretion. There was no significant correlation (r = 0.11) between secretion of adipose plasminogen activator inhibitor 1 and glucose transport. Furthermore, subcutaneous adipose tissue of 4 obese women (BMI 40 ± 4) incubated with TNF-α for 24 h showed a one-third concentration-dependent inhibition of insulin-stimulated glucose transport (P < 0.01). In conclusion, adipose TNF-α may be an important specific and local factor in adipose tissue that influences the ability of insulin to stimulate glucose transport in human fat cells, at least in obese women.