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

被引:23
|
作者
Srinivasa, Suman [1 ,2 ]
Suresh, Caroline [1 ,2 ]
Mottla, Jay [3 ]
Hamarneh, Sulaiman R. [2 ,4 ]
Irazoqui, Javier E. [2 ,5 ]
Frontera, Walter [6 ,7 ,8 ]
Torriani, Martin [2 ,9 ]
Stanley, Takara [1 ,2 ,10 ]
Makimura, Hideo [1 ,2 ]
机构
[1] Massachusetts Gen Hosp, Program Nutr Metab, 55 Fruit St,LON207, Boston, MA 02114 USA
[2] Harvard Univ, Sch Med, Boston, MA USA
[3] Georgetown Univ, Sch Med, Washington, DC USA
[4] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA
[5] Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Lab Comparat Immunol, Boston, MA 02114 USA
[6] Vanderbilt Univ, Med Ctr, Dept Phys Med & Rehabil, Nashville, TN USA
[7] Harvard Univ, Sch Med, Dept Phys Med & Rehabil, Spaulding Rehabil Hosp, Boston, MA USA
[8] Univ Puerto Rico, Sch Med, Dept Physiol, San Juan, PR USA
[9] Massachusetts Gen Hosp, Div Musculoskeletal Imaging & Intervent, Boston, MA 02114 USA
[10] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA
关键词
lrisin; FNDC5; Growth hormone; IGF-I; Skeletal muscle; Mitochondrial; Obesity; MESSENGER-RNA EXPRESSION; PHOSPHOCREATINE RECOVERY; IRISIN LEVELS; EXERCISE; SERUM; MYOKINE; HUMANS; BIOPSY; PLASMA; YOUNG;
D O I
10.1016/j.ghir.2015.12.008
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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 12 weeks of recombinant human GH (rhGH). Before and after treatment, they underwent P-31-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 (rho = 0.81, P = 0.005) and rate of PCr recovery (rho = 0.79, P = 0.006). Similar relationships of circulating irisin to IGF-I mRNA (rho = 0.63, P = 0.05) and rate of PCr recovery (rho = 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 PPAR gamma (rho = 0.73, P = 0.02 and rho = 0.85, P = 0.002), respectively. In addition, FNDC5 mRNA was correlated with skeletal muscle PGC-1 alpha (rho = 0.68, P = 0.03), NRF1 (rho = 0.66, P = 0.04) and TFAM (rho = 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. (C) 2015 Elsevier Ltd. All rights reserved.
引用
收藏
页码:36 / 41
页数:6
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