Differential Regulation of the p80 Tumor Necrosis Factor Receptor in Human Obesity and Insulin Resistance

Gökhan S Hotamisligil; Peter Arner; Richard L Atkinson; Bruce M Spiegelman

doi:10.2337/diab.46.3.451

Original Articles

Differential Regulation of the p80 Tumor Necrosis Factor Receptor in Human Obesity and Insulin Resistance

Gökhan S Hotamisligil,
Peter Arner,
Richard L Atkinson and
Bruce M Spiegelman

Division of Biological Sciences and Department of Nutrition, Harvard School of Public Health Boston, Massachusetts
Dana Farber Cancer Institute and Department of Cell Biology, Harvard Medical School Boston, Massachusetts
Department of Medicine, Karolinska Institute, Huddinge University Hospital Huddinge, Sweden
Department of Medicine, Medical College of Wisconsin Madison, Wisconsin

Address correspondence and reprint requests to Dr. Gökhan S. Hotamisligil, Harvard School of Public Health, 665 Huntington Ave., Boston, MA 02115. ghotamis{at}hsph.harvard.edu.

Diabetes 1997 Mar; 46(3): 451-455. https://doi.org/10.2337/diab.46.3.451

Abstract

Previous studies have shown that tumor necrosis factor (TNF)-α production from adipose tissue is elevated in rodent and human obesity and plays an important role in insulin resistance in experimental animal models. In this study, we examined the adipose expression of both TNF receptors (TNFR1 and TNFR2) in human obesity and demonstrated that obese female subjects express approximately twofold more TNFR2 mRNA in fat tissue and approximately sixfold more soluble TNFR2 in circulation relative to lean control subjects. In contrast, TNFR1 expression and protein levels were similar in these subjects. TNFR2 expression levels in adipose tissue were strongly correlated with BMI (r = 0.65, P < 0.001) and level of hyperinsulinemia (P < 0.001), an indirect measure of insulin resistance, as well as level of TNF-α mRNA expression in fat tissue (r = 0.56, P < 0.001). These results suggest that TNFR2 might play a role in human obesity by modulating the actions of TNF-α.