title: 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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Program in Nutritional Metabolism, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. Electronic address: ssrinivasa@mgh.harvard.edu.
authors.forename: Suman
authors.initials: S
authors.lastname: Srinivasa
authors.affiliation: Program in Nutritional Metabolism, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
authors.forename: Caroline
authors.initials: C
authors.lastname: Suresh
authors.affiliation: Georgetown University, School of Medicine, Washington, DC, USA.
authors.forename: Jay
authors.initials: J
authors.lastname: Mottla
authors.affiliation: Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
authors.forename: Sulaiman R
authors.initials: SR
authors.lastname: Hamarneh
authors.affiliation: Laboratory of Comparative Immunology, Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
authors.forename: Javier E
authors.initials: JE
authors.lastname: Irazoqui
authors.affiliation: Department of Physical Medicine and Rehabilitation, Vanderbilt University Medical Center, Nashville, TN, USA; Department of Physical Medicine and Rehabilitation, Harvard Medical School/Spaulding Rehabilitation Hospital, Boston, MA, USA; Department of Physiology, University of Puerto Rico School of Medicine, Puerto Rico.
authors.forename: Walter
authors.initials: W
authors.lastname: Frontera
authors.affiliation: Division of Musculoskeletal Imaging and Intervention, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
authors.forename: Martin
authors.initials: M
authors.lastname: Torriani
authors.affiliation: Program in Nutritional Metabolism, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA; Department of Pediatrics, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
authors.forename: Takara
authors.initials: T
authors.lastname: Stanley
authors.affiliation: Program in Nutritional Metabolism, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
authors.forename: Hideo
authors.initials: H
authors.lastname: Makimura
mesh_terms: D000293:Adolescent; D000328:Adult; D005353:Fibronectins / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression; D019382:Human Growth Hormone / Q000172:deficiency*; D006801:Humans; D007018:Hypopituitarism / Q000150:complications / Q000235:genetics / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000378:metabolism / Q000502:physiology*; D018482:Muscle, Skeletal / Q000378:metabolism; D009765:Obesity / Q000150:complications / Q000235:genetics* / Q000378:metabolism*; D055815:Young Adult
chemical_list: C577593:FNDC5 protein, human; D005353:Fibronectins; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I
keywords: FNDC5; Growth hormone; IGF-I; Irisin; Mitochondrial; Obesity; Skeletal muscle