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J Clin Endocrinol Metab. 2015 Feb;100(2):617-25. doi: 10.1210/jc.2014-2711. Epub 2014 Nov 6.

Relationship between serum IGF-1 and skeletal muscle IGF-1 mRNA expression to phosphocreatine recovery after exercise in obese men with reduced GH.

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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.



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.

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