Relationship Between Serum IGF-1 and Skeletal Muscle IGF-1 mRNA Expression to Phosphocreatine Recovery After Exercise in Obese Men With Reduced GH
Year: 2014
Type: article
Study design: Clinical Trial
Abstract: CONTEXT: GH and IGF-1 are believed to be physiological regulators of skeletal muscle mitochondria. OBJECTIVE: 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. DESIGN: 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. RESULTS: 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). CONCLUSION: These data demonstrate a novel association of skeletal muscle mitochondria with muscle IGF-1 mRNA expression, but independent of serum IGF-1 concentrations.
DOI: 10.1210/jc.2014-2711
Authors: Sulaiman R. Hamarneh, Caitlin A. Murphy, Cynthia W. Shih, Walter Frontera, Martin Torriani, Javier E. Irazoqui, Hideo Makimura
Language: English
Subfield: Endocrinology, Diabetes and Metabolism
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Funders: Pfizer, Massachusetts General Hospital, Harvard Catalyst, Novo Nordisk, National Institutes of Health, National Institute of General Medical Sciences, National Institute of Diabetes and Digestive and Kidney Diseases, National Center for Research Resources, NIH Clinical Center, National Center for Advancing Translational Sciences
Awards: Harvard Clinical and Translational Science Center (UL1), Nervous system control of intestinal host defense mediated by TFEB, Growth Hormone, Mitochondria, and Cardio-metabolic Complications of Obesity, G5887770846, Harvard Clinical and Translational Science Center (UL1), G8923804000, Center for the Study of Inflammatory Bowel Disease at Massachusetts General Hospital, Boston Area Nutrition Obesity Research Center (NORC)
OpenAlex ID: W1969935890