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.