Background: Recent studies show an increased adipose production of tumor necrosis factor-alpha (TNF-alpha) in human obesity. It was hypothesized from this finding and other data, that TNF-alpha may be a mediator of obesity-linked insulin resistance.
Objective: The aim of this study was to measure plasma concentrations of the two soluble TNF-alpha receptors, together with those of TNF-alpha in subjects with severe obesity with and without type 2 diabetes mellitus, in comparison to a lean control group, to examine whether plasma concentrations reflect an up-regulation of the TNF system in adipose tissue.
Patients and methods: Plasma concentrations of the two soluble TNF-alpha receptors were measured in 49 obese subjects (mean body mass index (BMI): 44.9 kg/m2, 95% confidence intervals (CI) 42.3-47.5 kg/m2, including 19 type 2 diabetic individuals) and 28 lean controls, by using a highly sensitive enzyme-linked immunoassay (ELISA) technique. TNF-alpha concentrations were determined in 28 obese (10 with diabetes) and 23 lean subjects.
Results: The obese subjects showed significantly higher plasma concentrations of the soluble p60 and p80 TNF receptor, respectively, compared to the lean control group, independent of the presence of diabetes. Multiple regression analysis, with the p80 TNF receptor as dependent variable, revealed that BMI and log insulin significantly affected the plasma concentration of this soluble receptor subtype, explaining 46% of the variance, whereas for the p60 TNF receptor, only BMI turned out to influence plasma concentrations. TNF-alpha plasma concentrations were not different between the three groups (Kruskal-Wallis test: P=0.34), but due to the low power of the test, an effect of obesity on TNF-alpha is not excluded.
Conclusion: These data indicate that plasma concentrations of both soluble TNF receptors are elevated in obesity and insulin resistance, possibly as a function of excess body fat. The reported adipose overexpression of TNF-alpha does not seem to be reflected by elevated plasma concentrations, suggesting a primarily local role of the cytokine.