Visceral obesity and plasma glucose-insulin homeostasis:: Contributions of interleukin-6 and tumor necrosis factor-α in men

Objective: This study examined the relationships of two inflammatory cytokines, IL-6 and TNF-alpha, to visceral adiposity and indices of plasma glucose-insulin homeostasis. Research Design and Methods: Plasma levels of IL-6 and TNF-alpha were measured in 189 untreated asymptomatic men (aged 43.7 +/- 7.8 yr; body mass index 29.0 +/- 4.3 kg/m(2); waist girth 98.6 +/- 10.3 cm). Results: Significant and positive associations were found between both cytokines with adiposity and adipose tissue distribution indices (0.15 <= r < 0.32; P < 0.05) as well as plasma glucose-insulin homeostasis variables (0.22 <= r < 0.28; P < 0.05). Comparison of two subgroups, each composed of 32 overweight men (>= 25 kg/m(2)) with similar body mass index values (28.7 kg/m(2) in both groups) but with markedly different levels of visceral adipose tissue (< vs. >= 130 cm(2)), revealed significant differences only for IL-6 levels (1.42 +/- 1.15 vs. 0.86 +/- 0.52 pg/ml; P < 0.02 for men with high vs. low visceral adipose tissue, respectively). Finally, when subjects were stratified on the basis of their respective concentrations of IL-6 and TNF-alpha(using the 50th percentile of their overall distribution), an ANOVA revealed an independent contribution of IL-6 to the variation of fasting insulin (P < 0.01) and each of these two cytokines to the variation of insulin levels measured after a 75-g oral glucose challenge (P < 0.01 for IL-6 and P < 0.05 for TNF-alpha). Conclusions: Because IL-6 appeared to be clearly associated with visceral adiposity, TNF-alpha rather showed associations with indices of total body fatness. Thus, TNF-alpha may contribute to the insulin resistance of overall obesity, whereas IL-6 may be one of the mediators of the hyperinsulinemic state specifically related to excess visceral adiposity.