Time-Dependent Changes in Increased Levels of Plasma Irisin and Muscle PGC-1α and FNDC5 after Exercise in Mice

Exercise induces the expression of peroxisome proliferator-activated receptor gamma co-activator 1-alpha (PGC-1 alpha) in skeletal muscle, which promotes the cleavage of fibronectin type Ill domain-containing protein 5 (FNDC5) to irisin. To explore the relationship between irisin and its regulators, we analyzed the plasma irisin levels and the muscle levels of FNDC5 and PGC-1 alpha after exercise. Male C57BL/6J mice underwent a treadmill exercise (60% of VO2max.) for 30 min or one hour (h), and blood and gastrocnemius samples were collected before exercise (pre-exercise), immediately after exercise, and during 24-h recovery after 1-h exercise. We found that plasma irisin levels were significantly increased during exercise (P < 0.05), while FNDC5 protein levels were not significantly increased. Moreover, PGC-1 alpha mRNA and protein levels were significantly increased during 30-min exercise, but were decreased during 1-h exercise. After 1-h exercise, the irisin levels peaked at 6 h (20.71 +/- 0.25 ng/ml) and decreased to pre-exercise levels by 24 h (15.45 +/- 0.27 ng/ml). Likewise, PGC-1 alpha mRNA and protein levels were increased at 1 h and maintained at elevated levels for 6 h; thereafter, the expression levels of PGC1-alpha protein were decreased to pre-exercise levels at 12 h. Thus, the restoration of PGC-1 alpha expression to the pre-exercise levels was followed by the decrease in plasma irisin levels. By contrast, during 24-h recovery, the expression levels of FNDC5 mRNA and protein were maintained at elevated levels. These results suggest that the coordinated expression of FNDC5 and PGC-1 alpha may contribute to the increased levels of plasma irisin after exercise.