To delineate the metabolic shifts underlying our observations we performed NMR-based serum metabolomics analysis. However, given the significant reduction in serum fatty acids and glucose in the EX group, surprisingly subtle changes were observed in serum metabolites levels. No change in leptin or adiponectin concentrations was observed after exercise training, whilst dieting significantly find more decreased leptin and increased adiponectin levels, indicating that the reduction in serum glucose and free fatty acids did not result from insulin sensitizing effects of adipokines.36 Exercise training was not associated with

changes in beta hydroxybutyrate to acetoacetate ratio or lactate to pyruvate ratio which are indicators of redox state in mitochondria,37 suggesting

that the beneficial effects of aerobic selleckchem exercise on glucose and lipid metabolism was not ascribed to reduced reactive oxygen species production. Exercise resulted in increased serum phenylalanine and glycine and, to a lesser significant extent, tyrosine and histidine concentrations. Increased levels of serum phenylalanine and tyrosine have been associated with obesity and insulin resistance in previous studies,38 whereas increased serum glycine has been associated with increased insulin sensitivity and fatty acid oxidation.39 Thus, reductions in insulin resistance and serum free fatty acids in the EX group may have resulted from recovery of serum glycine concentrations and subsequent increase in mitochondrial function. Moreover, it has been shown that, in sedentary subjects, greater metabolic stress results in adaptation manifested by improved muscular mitochondrial biogenesis and enhanced fatty acid oxidation,40 which thereby may accelerate fatty acid removal from circulation.41 Calpain Therefore, it is plausible that the mitochondrial adaptation to progressive exercise training was responsible for the reduction in free fatty acids and the subsequent reduction in insulin resistance in

the present study. The strength of our randomized trial study design reached the methodological requirements of physical activity trials42 to provide reliable and valid evidence on the effects of exercise. Our design also focused on moderate progressive aerobic exercise training because this is what is recommended in most public health guidelines for adults.43 All the samples were analyzed in the same laboratory at the same time by a same person. However, the current study is limited by the homogeneous subjects consisting Finnish women. Therefore, our results may not be transferrable to the general population. The fact that we used bioimpedance instead of dual-energy X-ray absorptiometry or magnetic resonance imaging to define body composition may predispose our results to measurement error.44 Furthermore, VO2max was defined by bicycle ergometer, while exercise training consisted of Nordic walking.