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Visceral Obesity and Plasma Glucose-Insulin Homeostasis: Contributions of Interleukin-6 and Tumor Necrosis Factor- in Men

Québec Heart Institute (A.C., I.L., N.A., J.-P.D.), Hôpital Laval Research Centre, Hôpital Laval, Québec, Canada G1V 4G5; Department of Anatomy and Physiology (A.C.) and Division of Kinesiology (A.T., J.-P.D.), Department of Social and Preventive Medicine, Université Laval, Québec, Canada G1K 7P4; and Lipid Research Centre (J.B.), Centre Hospitalier de l’Université Laval Research Centre, Québec, Canada G1V 4G2

Address all correspondence and requests for reprints to: Jean-Pierre Després, Ph.D., F.A.H.A., Director of Research, Québec Heart Institute, Hôpital Laval Research Centre, Hôpital Laval, 2725, Chemin Sainte-Foy, Pavilion Marguerite-D’Youville, 4th Floor, Québec, Canada G1V 4G5. E-mail: jean-pierre.despres{at}crhl.ulaval.ca.

Objective: This study examined the relationships of two inflammatory cytokines, IL-6 and TNF-, to visceral adiposity and indices of plasma glucose-insulin homeostasis.

Research Design and Methods: Plasma levels of IL-6 and TNF- were measured in 189 untreated asymptomatic men (aged 43.7 ± 7.8 yr; body mass index 29.0 ± 4.3 kg/m²; 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/m²) with similar body mass index values (28.7 kg/m² in both groups) but with markedly different levels of visceral adipose tissue (< vs. 130 cm²), 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- (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-).

Conclusions: Because IL-6 appeared to be clearly associated with visceral adiposity, TNF- rather showed associations with indices of total body fatness. Thus, TNF- 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.

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