Changes in tumor necrosis factor-alpha system and insulin sensitivity during an exercise training program in obese women with normal and impaired glucose tolerance

Objective: Tumor necrosis factor-a (TNF alpha.)plays an important role in t he pathogenesis of insulin resistance and type 2 diabetes. Plasma levels of the soluble (s) fractions of TNF alpha receptors, especially sTNFR2, are g ood indicators of TNT alpha system activation in obesity. The aim of the pr esent study was to assess the effect of exercise training on the TNF alpha system and to evaluate the relationship with changes in insulin sensitivity . Design and methods: Sixteen obese women (body mass index (BMI)> 27.8 kg/m(2 )), 8 with normal (NGT) and 8 with impaired glucose tolerance (IGT), partic ipated in an exercise training program which lasted for 12 weeks and includ ed exercise performed on a bicycle ergometer at an individual intensity of 70% maximal heart rate, for 30 min, 5 days a week. Anthropometrical measure ments and blood biochemical analyses were performed, and plasma TNF alpha, sTNFR1 and sTNFR2 levels were assessed. Insulin sensitivity was evaluated u sing the hyperinsulinemic euglycemic clamp technique (insulin infusion: 50 mU X kg(-1) X h(-1)). Results: At baseline, despite similar anthropometrical parameters, IGT subj ects were markedly more insulin resistant and had higher TNF alpha and sTNF R2 concentrations. Exercise training increased insulin sensitivity and decr eased TNF alpha and sTNFR2 levels, while sTNFRl remained unchanged. The dec rease in sTNFR2 was significantly related to the increase in insulin sensit ivity; that relationship remained significant after adjustment for the conc urrent changes in BMI, waist circumference, percentage of body fat, plasma glucose, insulin and free fatty acids. Conclusions: Regular physical exercise decreases TNF alpha, system activity and that decrease may be responsible for the concurrent increase in insuli n sensitivity.