title: Growth hormone signaling in muscle and adipose tissue of obese human subjects: associations with measures of body composition and interaction with resveratrol treatment.
abstract: BACKGROUND
  Growth hormone (GH) secretion is reduced in obesity, despite normal serum insulin-like growth factor I (IGF-1) levels, but the association between obesity and the GH signaling is unknown. Furthermore, SIRT1, an nicotinamide adenine dinucleotide-dependent protein deacetylase, reduces hepatic IGF-1 production in mice via blunting of GH-induced STAT5 signaling.
  
  
  OBJECTIVE
  To study GH signaling in muscle and fat in obese subjects and the interaction with concomitant administration of the putative SIRT1 activator resveratrol, and to assess the effects of inhibiting or knocking down SIRT1 on GH regulated genes in vitro.
  
  
  METHODS
  Twenty-four obese males were examined in a randomized, double blinded, parallel-group study with resveratrol or placebo treatment for 5 weeks followed by a GH bolus. Muscle and fat biopsies were collected before and after GH. Body composition was assessed by DEXA and MRI.
  
  
  METHODS
  (1) Effect of body composition and age on GH-stimulated STAT5b phosphorylation and IGF-1, SOCS2, and CISH mRNA in muscle and fat. (2) The impact of resveratrol treatment on GH activity. (3) Impact of inhibiting or knocking down SIRT1 on effects of GH in vitro.
  
  
  RESULTS
  Significant GH-induced STAT5b phosphorylation in muscle and fat in obese subjects was recorded together with increased CISH and SOCS2 mRNA. GH-induced STAT5b phosphorylation in muscle correlated positively with age [r = 0.53, p < 0.01], but not with body composition. Resveratrol administration had no impact on body composition, serum IGF-1, or GH signaling in vivo, and SIRT1 knock down or inhibition did not affect GH signaling in vitro.
  
  
  CONCLUSIONS
  (1) GH induced STAT5b phosphorylation is detectable in muscle and fat in adult males with simple obesity, but is not determined by body composition. (2) Resveratrol supplementation does not impact circulating IGF-1 levels or GH signaling in human muscle and fat. (3) Our data speak against a major impact of SIRT1on GH action in human subjects.
authors: Research Laboratory for Biochemical Pathology (B.F.C., N.J.), Institute of Clinical Medicine, Aarhus University, 8000 Aarhus, Denmark; Department of Endocrinology and Internal Medicine (M.M.P., S.B.P., N.M., J.O.L.J.), Aarhus University Hospital, 8000 Aarhus, Denmark; Department of Molecular Medicine (N.J.), Aarhus University Hospital, 8000 Aarhus N, Denmark; Department of Anesthesiology and Kogod Center on Aging (C.E., E.N.C.), Mayo Clinic, Rochester, Minnesota 55905; Metabolism and Aging Laboratory (C.E.), Institut Pasteur, 11400 Montevideo, Uruguay.
authors: Berthil F
authors: BF
authors: Clasen
authors: Morten M
authors: MM
authors: Poulsen
authors: Carlos
authors: C
authors: Escande
authors: Steen B
authors: SB
authors: Pedersen
authors: Niels
authors: N
authors: Møller
authors: Eduardo N
authors: EN
authors: Chini
authors: Niels
authors: N
authors: Jessen
authors: Jens O L
authors: JO
authors: Jørgensen
mesh_terms: D041721:3T3-L1 Cells; D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001823:Body Composition / Q000187:drug effects / Q000502:physiology*; D004311:Double-Blind Method; D019382:Human Growth Hormone / Q000502:physiology*; D051379:Mice; D009132:Muscles / Q000187:drug effects / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism* / Q000503:physiopathology; D000077185:Resveratrol; D050799:STAT5 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D056564:Sirtuin 1 / Q000494:pharmacology; D013267:Stilbenes / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D050799:STAT5 Transcription Factor; C494095:STAT5B protein, human; D013267:Stilbenes; D019382:Human Growth Hormone; C447939:SIRT1 protein, human; D056564:Sirtuin 1; D000077185:Resveratrol