Are skeletal muscle FNDC5 gene expression and irisin release regulated by exercise and related to health?

Abstract

Recently, contradictory findings have been reported concerning the function of irisin and its precursor gene, skeletal muscle FNDC5, in energy homeostasis, and the associated regulatory role of exercise and PGC-1α. We therefore evaluated whether muscle FNDC5 mRNA and serum irisin are exercise responsive and whether PGC-1α expression is associated with FNDC5 expression. The male subjects in the study performed single exercises: (1) 1 h low-intensity aerobic exercise (AE) (middle-aged, n = 17), (2) a heavy-intensity resistance exercise (RE) bout (young n = 10, older n = 11) (27 vs. 62 years), (3) long-term 21 weeks endurance exercise (EE) training alone (twice a week, middle-aged, n = 9), or (4) combined EE and RE training (both twice a week, middle-aged, n = 9). Skeletal muscle mRNA expression was analysed by quantitative PCR and serum irisin by ELISA. No significant changes were observed in skeletal muscle PGC-1α, FNDC5 and serum irisin after AE, EE training or combined EE + RE training. However, a single RE bout increased PGC-1α by 4-fold in young and by 2-fold in older men, while FNDC5 mRNA only increased in young men post-RE, by 1.4-fold. Changes in PGC-1α or serum irisin were not consistently accompanied by changes in FNDC5. In conclusion, for the most part, neither longer-term nor single exercise markedly increases skeletal muscle FNDC5 expression or serum irisin. Therefore their changes in response to exercise are probably random and not consistent excluding the confirmation of any definitive link between exercise and FNDC5 expression and irisin release in humans. Moreover, irisin and FNDC5 were not associated with glucose tolerance and being overweight, or with metabolic disturbances, respectively. Finally, factor(s) other than PGC-1α and transcription may regulate FNDC5 expression.

Figure 1

Changes of PGC-1α (A), FNDC5 mRNA expression (B) and serum irisin (C) in middle-aged, non-diabetic and previously untrained men after a 1 h low-intensity (50%) aerobic exercise (AE) performed with bicycle ergometry (n= 17); 21 weeks endurance training (EE, n= 9); combined endurance + resistance training (EE + RE, n= 9), and in age-matched non-exercised controls (Con, n= 2). In A, B and C the error bars represent mean values and the whiskers are 95% confidence intervals. The circles represent individual values. D, individual responses to exercise. Each line represents one individual and links the change of PGC-1α to the change of FNDC5 mRNA after exercise. E, individual responses to exercise. Each line represents one individual and links the change of FNDC5 mRNA to the change of serum irisin after exercise. (Data are pooled from panels A and B.) F, serum irisin concentrations (ng ml⁻¹) before and after AE. G, serum irisin concentrations (ng ml⁻¹) before and after EE and combined EE + RE. H, serum irisin concentrations after 1, 15 and 30 min of a heavy-exercise bout.

Figure 2

Skeletal muscle mRNA fold changes of PGC-1α and FNDC5 after 1 h and 48 h of a single resistance exercise bout (5 × 10 RM leg press) in young (A, n= 10) and older (B, n= 11) men. In A and B the error bars represent mean values and the whiskers are 95% confidence intervals. The circles represent individual values. C–F, individual responses to exercise in young (C and D) and older (E and F) men. Each line represents one individual and links the change of PGC-1α to the change of FNDC5 mRNA.