title: Secretion of tumor necrosis factor-alpha shows a strong relationship to insulin-stimulated glucose transport in human adipose tissue.
abstract: Some animal models suggest that tumor necrosis factor (TNF)-alpha 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-alpha levels and insulin sensitivity. In the present study, the potential local role of TNF-alpha 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-alpha 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-alpha 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-A for 24 h showed a one-third concentration-dependent inhibition of insulin-stimulated glucose transport (P < 0.01). In conclusion, adipose TNF-alpha 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.
authors.affiliation: Karolinska Institute, Clinical Research Center, and the Department of Medicine, Huddinge University Hospital, Stockholm, Sweden.
authors.forename: P
authors.initials: P
authors.lastname: Löfgren
authors.forename: V
authors.initials: V
authors.lastname: van Harmelen
authors.forename: S
authors.initials: S
authors.lastname: Reynisdottir
authors.forename: E
authors.initials: E
authors.lastname: Näslund
authors.forename: M
authors.initials: M
authors.lastname: Rydén
authors.forename: S
authors.initials: S
authors.lastname: Rössner
authors.forename: P
authors.initials: P
authors.lastname: Arner
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism*; D000328:Adult; D001692:Biological Transport / Q000187:drug effects; D005260:Female; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D008875:Middle Aged; D009765:Obesity / Q000378:metabolism; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D007328:Insulin; D017395:Plasminogen Activator Inhibitor 1; D014409:Tumor Necrosis Factor-alpha; D005947:Glucose