FNDC5 relates to skeletal muscle IGF-I and mitochondrial function and gene expression in obese men with reduced growth hormone.

ABSTRACT

OBJECTIVE: To investigate the relationship of skeletal muscle FNDC5 mRNA expression and circulating irisin to the GH/IGF-I axis and to skeletal muscle mitochondrial function and mitochondria-related gene expression in obese men. DESIGN: Fifteen abdominally obese men with reduced growth hormone received 12weeks of recombinant human GH (rhGH). Before and after treatment, they underwent (31)P-magnetic resonance spectroscopy to evaluate phosphocreatine (PCr) recovery as a measure of mitochondrial function and skeletal muscle biopsy to assess expression of mitochondrial-related genes. Serum irisin and IGF-I and skeletal muscle FNDC5 and IGF-I mRNA were measured. RESULTS: At baseline, skeletal muscle FNDC5 mRNA was significantly and positively associated with IGF-I mRNA (ρ=0.81, P=0.005) and rate of PCr recovery (ρ=0.79, P=0.006). Similar relationships of circulating irisin to IGF-I mRNA (ρ=0.63, P=0.05) and rate of PCr recovery (ρ=0.48, P=0.08) were demonstrated, but were not as robust as those with muscle FNDC5 expression. Both serum irisin and skeletal muscle FNDC5 mRNA were significantly associated with PPARγ (ρ=0.73, P=0.02 and ρ=0.85, P=0.002), respectively. In addition, FNDC5 mRNA was correlated with skeletal muscle PGC-1α (ρ=0.68, P=0.03), NRF1 (ρ=0.66, P=0.04) and TFAM (ρ=0.79, P=0.007) mRNA. Neither serum irisin nor muscle mRNA expression of FNDC5 changed with rhGH treatment. CONCLUSION: These novel data in skeletal muscle demonstrate that local expression of FNDC5 is associated with mRNA expression of IGF-I and mitochondrial function and mitochondria-related gene expression in obese subjects with reduced growth hormone and suggest a potential role for FNDC5 acting locally in muscle in a low GH state. Further studies are needed to clarify the relationship between the GH/IGF-I axis and irisin.