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This Article Full Text Full Text (PDF) All Versions of this Article: 294/6/E1127    most recent 00010.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Trepp, R. Articles by Christ, E. R. Search for Related Content PubMed PubMed Citation Articles by Trepp, R. Articles by Christ, E. R.

Effect of GH on human skeletal muscle lipid metabolism in GH deficiency

¹Division of Endocrinology, Diabetology and Clinical Nutrition, Inselspital, Bern University Hospital and University of Bern; ²Department of Clinical Research (Magnetic Resonance Spectroscopy and Methodology), University of Bern; ³Department of Systematic Anatomy; and ⁴Cardiovascular Prevention and Rehabilitation, Department of Cardiology, Inselspital, University of Bern, Bern, Switzerland

Submitted 4 January 2008 ; accepted in final form 13 April 2008

Adult-onset growth hormone (GH) deficiency (GHD) is associated with insulin resistance and decreased exercise capacity. Intramyocellular lipids (IMCL) depend on training status, diet, and insulin sensitivity. Using magnetic resonance spectroscopy, we studied IMCL content following physical activity (IMCL-depleted) and high-fat diet (IMCL-repleted) in 15 patients with GHD before and after 4 mo of GH replacement therapy (GHRT) and in 11 healthy control subjects. Measurements of insulin resistance and exercise capacity were performed and skeletal muscle biopsies were carried out to assess expression of mRNA of key enzymes involved in skeletal muscle lipid metabolism by real-time PCR and ultrastructure by electron microscopy. Compared with control subjects, patients with GHD showed significantly higher difference between IMCL-depleted and IMCL-repleted. GHRT resulted in an increase in skeletal muscle mRNA expression of IGF-I, hormone-sensitive lipase, and a tendency for an increase in fatty acid binding protein-3. Electron microscopy examination did not reveal significant differences after GHRT. In conclusion, variation of IMCL may be increased in patients with GHD compared with healthy control subjects. Qualitative changes within the skeletal muscle (i.e., an increase in free fatty acids availability from systemic and/or local sources) may contribute to the increase in insulin resistance and possibly to the improvement of exercise capacity after GHRT. The upregulation of IGF-I mRNA suggests a paracrine/autocrine role of IGF-I on skeletal muscle.

intramyocellular lipids; insulin resistance; magnetic resonance spectroscopy; exercise capacity