Suman Srinivasa1, Caroline Suresh2, Jay Mottla3, Sulaiman R Hamarneh4, Javier E Irazoqui5, Walter Frontera6, Martin Torriani7, Takara Stanley8, Hideo Makimura2. 1. Program in Nutritional Metabolism, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. Electronic address: ssrinivasa@mgh.harvard.edu. 2. Program in Nutritional Metabolism, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. 3. Georgetown University, School of Medicine, Washington, DC, USA. 4. Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. 5. Laboratory of Comparative Immunology, Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. 6. 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. 7. Division of Musculoskeletal Imaging and Intervention, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. 8. 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.
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.
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 obesemen. DESIGN: Fifteen abdominally obesemen with reduced growth hormone received 12weeks of recombinant humanGH (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.
Authors: P Dietrichson; J Coakley; P E Smith; R D Griffiths; T R Helliwell; R H Edwards Journal: J Neurol Neurosurg Psychiatry Date: 1987-11 Impact factor: 10.154
Authors: Stella S Daskalopoulou; Alexandra B Cooke; Yessica-Haydee Gomez; Andrew F Mutter; Andreas Filippaios; Ertirea T Mesfum; Christos S Mantzoros Journal: Eur J Endocrinol Date: 2014-06-11 Impact factor: 6.664
Authors: Hideo Makimura; Takara Stanley; David Mun; Cindy Chen; Jeffrey Wei; Jean M Connelly; Linda C Hemphill; Steven K Grinspoon Journal: J Clin Endocrinol Metab Date: 2009-10-16 Impact factor: 5.958
Authors: Jun Wu; Pontus Boström; Lauren M Sparks; Li Ye; Jang Hyun Choi; An-Hoa Giang; Melin Khandekar; Kirsi A Virtanen; Pirjo Nuutila; Gert Schaart; Kexin Huang; Hua Tu; Wouter D van Marken Lichtenbelt; Joris Hoeks; Sven Enerbäck; Patrick Schrauwen; Bruce M Spiegelman Journal: Cell Date: 2012-07-12 Impact factor: 41.582
Authors: Pontus Boström; Jun Wu; Mark P Jedrychowski; Anisha Korde; Li Ye; James C Lo; Kyle A Rasbach; Elisabeth Almer Boström; Jang Hyun Choi; Jonathan Z Long; Shingo Kajimura; Maria Cristina Zingaretti; Birgitte F Vind; Hua Tu; Saverio Cinti; Kurt Højlund; Steven P Gygi; Bruce M Spiegelman Journal: Nature Date: 2012-01-11 Impact factor: 49.962
Authors: Lara Pena-Bello; Sonia Pértega-Diaz; Susana Sangiao-Alvarellos; Elena Outeiriño-Blanco; Raquel Eiras-Leal; Bárbara Varela-Rodriguez; Paula Juiz-Valiña; Miguel Pérez-Fontán; María Cordido; Fernando Cordido Journal: PLoS One Date: 2016-07-29 Impact factor: 3.240