Effect of GH on human skeletal muscle lipid metabolism in GH deficiency.
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.
Trepp
Roman
R
Division of Endocrinology, Diabetology and Clinical Nutrition, Inselspital, Bern University Hospital and University of Bern, Bern, Switzerland.
Flück
Martin
M
Stettler
Christoph
C
Boesch
Chris
C
Ith
Michael
M
Kreis
Roland
R
Hoppeler
Hans
H
Howald
Hans
H
Schmid
Jean-Paul
JP
Diem
Peter
P
Christ
Emanuel R
ER
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
D050556:Fatty Acid-Binding Proteins; D019382:Human Growth Hormone; D012313:RNA; D007334:Insulin-Like Growth Factor I; D002787:Sterol Esterase