title: Effect of GH on human skeletal muscle lipid metabolism in GH deficiency.
abstract: 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.
authors.affiliation: Division of Endocrinology, Diabetology and Clinical Nutrition, Inselspital, Bern University Hospital and University of Bern, Bern, Switzerland.
authors.forename: Roman
authors.initials: R
authors.lastname: Trepp
authors.forename: Martin
authors.initials: M
authors.lastname: Flück
authors.forename: Christoph
authors.initials: C
authors.lastname: Stettler
authors.forename: Chris
authors.initials: C
authors.lastname: Boesch
authors.forename: Michael
authors.initials: M
authors.lastname: Ith
authors.forename: Roland
authors.initials: R
authors.lastname: Kreis
authors.forename: Hans
authors.initials: H
authors.lastname: Hoppeler
authors.forename: Hans
authors.initials: H
authors.lastname: Howald
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Schmid
authors.forename: Peter
authors.initials: P
authors.lastname: Diem
authors.forename: Emanuel R
authors.initials: ER
authors.lastname: Christ
mesh_terms: D000328:Adult; D001706:Biopsy; D002153:Calorimetry, Indirect; D016552:Ergometry; D050556:Fatty Acid-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D020249:Hormone Replacement Therapy; D019382:Human Growth Hormone / Q000008:administration & dosage* / Q000172:deficiency / Q000502:physiology; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000201:enzymology / Q000378:metabolism*; D010809:Physical Fitness / Q000502:physiology; D016133:Polymerase Chain Reaction; D012313:RNA / Q000737:chemistry / Q000235:genetics; D002787:Sterol Esterase / Q000235:genetics / Q000378:metabolism
chemical_list: D050556:Fatty Acid-Binding Proteins; D019382:Human Growth Hormone; D012313:RNA; D007334:Insulin-Like Growth Factor I; D002787:Sterol Esterase