Hamarneh Sulaiman R, Murphy Caitlin A, Shih Cynthia W, Frontera Walter, Torriani Martin, Irazoqui Javier E, Makimura Hideo
Department of Surgery (S.R.H.), Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114; Program in Nutritional Metabolism (C.A.M., C.W.S., H.M.), Massachusetts General Hospital, Boston, Massachusetts 02114; Harvard College (C.W.S.), Boston, Massachusetts 02138; Department of Physical Medicine and Rehabilitation (W.F.), Vanderbilt University Medical Center, Nashville, Tennessee 37212; Department of Physical Medicine and Rehabilitation (W.F.), Harvard Medical School/Spaulding Rehabilitation Hospital, Boston, Massachusetts 02114; Department of Physiology (W.F.), University of Puerto Rico School of Medicine, San Juan, Puerto Rico 00936; and Department of Radiology (M.T.), Laboratory of Comparative Immunology, Center for the Study of Inflammatory Bowel Disease (J.E.I.), and Neuroendocrine Unit (H.M.), Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114.
J Clin Endocrinol Metab. 2015 Feb;100(2):617-25. doi: 10.1210/jc.2014-2711. Epub 2014 Nov 6.
GH and IGF-1 are believed to be physiological regulators of skeletal muscle mitochondria.
The objective of this study was to examine the relationship between GH/IGF-1 and skeletal muscle mitochondria in obese subjects with reduced GH secretion in more detail.
Fifteen abdominally obese men with reduced GH secretion were treated for 12 weeks with recombinant human GH. Subjects underwent (31)P-magnetic resonance spectroscopy to assess phosphocreatine (PCr) recovery as an in vivo measure of skeletal muscle mitochondrial function and percutaneous muscle biopsies to assess mRNA expression of IGF-1 and mitochondrial-related genes at baseline and 12 weeks.
At baseline, skeletal muscle IGF-1 mRNA expression was significantly associated with PCr recovery (r = 0.79; P = .01) and nuclear respiratory factor-1 (r = 0.87; P = .001), mitochondrial transcription factor A (r = 0.86; P = .001), peroxisome proliferator-activated receptor (PPAR)γ (r = 0.72; P = .02), and PPARα (r = 0.75; P = .01) mRNA expression, and trended to an association with PPARγ coactivator 1-α (r = 0.59; P = .07) mRNA expression. However, serum IGF-1 concentration was not associated with PCr recovery or any mitochondrial gene expression (all P > .10). Administration of recombinant human GH increased both serum IGF-1 (change, 218 ± 29 μg/L; P < .0001) and IGF-1 mRNA in muscle (fold change, 2.1 ± 0.3; P = .002). Increases in serum IGF-1 were associated with improvements in total body fat (r = -0.53; P = .04), trunk fat (r = -0.55; P = .03), and lean mass (r = 0.58; P = .02), but not with PCr recovery (P > .10). Conversely, increase in muscle IGF-1 mRNA was associated with improvements in PCr recovery (r = 0.74; P = .02), but not with body composition parameters (P > .10).
These data demonstrate a novel association of skeletal muscle mitochondria with muscle IGF-1 mRNA expression, but independent of serum IGF-1 concentrations.
生长激素（GH）和胰岛素样生长因子-1（IGF-1）被认为是骨骼肌线粒体的生理调节因子。
本研究的目的是更详细地研究生长激素/胰岛素样生长因子-1与生长激素分泌减少的肥胖受试者骨骼肌线粒体之间的关系。
15名生长激素分泌减少的腹型肥胖男性接受重组人生长激素治疗12周。受试者接受磷磁共振波谱检查以评估磷酸肌酸（PCr）恢复情况，作为骨骼肌线粒体功能的体内测量指标，并在基线和12周时进行经皮肌肉活检以评估IGF-1和线粒体相关基因的mRNA表达。
在基线时，骨骼肌IGF-1 mRNA表达与PCr恢复（r = 0.79；P = 0.01）、核呼吸因子-1（r = 0.87；P = 0.001）、线粒体转录因子A（r = 0.86；P = 0.001）、过氧化物酶体增殖物激活受体（PPAR）γ（r = 0.72；P = 0.02）和PPARα（r = 0.75；P = 0.01）的mRNA表达显著相关，并与PPARγ共激活因子1-α（r = 0.59；P = 0.07）的mRNA表达呈趋势性相关。然而，血清IGF-1浓度与PCr恢复或任何线粒体基因表达均无关联（所有P > 0.10）。给予重组人生长激素可增加血清IGF-1（变化值，218±29μg/L；P < 0.0001）和肌肉中的IGF-1 mRNA（倍数变化，2.1±0.3；P = 0.002）。血清IGF-1的增加与全身脂肪（r = -0.53；P = 0.04）、躯干脂肪（r = -0.55；P = 0.03）和瘦体重（r = 0.58；P = 0.02）的改善相关，但与PCr恢复无关（P > 0.10）。相反，肌肉IGF-1 mRNA的增加与PCr恢复的改善相关（r = 0.74；P = 0.02），但与身体成分参数无关（P > 0.10）。
这些数据表明骨骼肌线粒体与肌肉IGF-1 mRNA表达存在新的关联，但独立于血清IGF-1浓度。
