The effects of training on FNDC5/irisin and its association with fitness and metabolic marker improvements induced by training have been poorly investigated in humans. Thus, the present study assessed the effects of combined training (CT) on FNDC5/irisin levels, metabolic markers and fitness adaptations in obese men. Middle-age obese men (age 49.13 +/- 5.75, body mass index (BMI) 30.86 +/- 1.63) were randomly distributed in the CT group (n = 12) and control group (CG n = 10). The CT consisted of strength followed by aerobic training, 3 times/week, for 24 weeks. Body composition, physical fitness, plasma FNDC5/irisin, biochemical markers and metabolic scores/index were evaluated. CT maintained FNDC5/irisin levels (micro g/mL) (pre 4.15 +/- 0.32, post 4.21 +/- 0.32; p = 0.96) and improved body composition, metabolic and physical fitness markers. In the CG, decreased FNDC5/irisin (micro g/mL) (pre 4.36 +/- 0.23, post 3.57 +/- 0.94; p = 0.01) and reduced strength (supine exercise/kg) (pre 71 +/- 14.7, post 60.1 +/- 14.05; p < 0.01) were observed, along with a trend to increase HOMA-IR (pre 2.63 +/- 1.11, post 3.14 +/- 1.27; p = 0.07) and other indicators of metabolic deterioration. An inverse correlation was found between the change (delta%) in levels of FNDC5/irisin and delta% glucose, delta% total cholesterol, delta% triglycerides and delta% waist circumference, in addition to a positive relation with delta% muscle strength. In conclusion, CT maintained FNDC5/irisin levels and provided metabolic and fitness benefits. The correlation between FNDC5/irisin changes and metabolic parameters, as well as the FNDC5/irisin reduction associated with fitness and metabolic worsening in the CG, suggests a relationship between FNDC5/irisin and a healthy metabolic status in humans.

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