We investigated the integrated effects of an aerobic training program on circulatory levels of the metabotrophic factors (metabotrophins) nerve growth factor (NGF), brain derived neurotrophic factor (BDNF) and insulin like growth factor-1 (IGF-1), and anabolic state (testosterone/cortisol ratio) in middle aged males with metabolic syndrome (MetS). Thirty subjects (age: 58.23 ± 5.25 years, weight: 95.00 ± 8.26 kg, height: 173 ± 7.03 cm, VO2peak: 19.96 ± 4.18 ml kg.min-1) were randomized into exercise (n=16) and control, non-exercised (n=14) group. The exercise group participated in eight weeks of aerobic training program (3 sessions/week at 50%-60% of VO2 peak). Fasting blood samples were taken at baseline and after training and VO2 peak, insulin sensitivity and an overall metabolic syndrome Z score (Z MetS) were calculated. Aerobic training significantly increased insulin sensitivity, Vo2 peak, plasma HDL and serum levels of NFG, BDNF, IGF-1 and testosterone (P