Berthil F Clasen1, Morten M Poulsen, Carlos Escande, Steen B Pedersen, Niels Møller, Eduardo N Chini, Niels Jessen, Jens O L Jørgensen. 1. 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.
Abstract
CONTEXT: 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. DESIGN AND PARTICIPANTS: 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. MAIN OUTCOME MEASURE: (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. CONCLUSION: (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.
RCT Entities:
CONTEXT: 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. DESIGN AND PARTICIPANTS: 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. MAIN OUTCOME MEASURE: (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. CONCLUSION: (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: Bipradas Roy; Mary E Curtis; Letimicia S Fears; Samuel N Nahashon; Hugh M Fentress Journal: Front Physiol Date: 2016-09-29 Impact factor: 4.566
Authors: Katrine L Høyer; Morten L Høgild; Edward O List; Kevin Y Lee; Emily Kissinger; Rita Sharma; Nils Erik Magnusson; Vishwajeet Puri; John J Kopchick; Jens O L Jørgensen; Niels Jessen Journal: Physiol Rep Date: 2020-02
Authors: Astrid Johannesson Hjelholt; Kevin Y Lee; Mai Christiansen Arlien-Søborg; Steen Bønløkke Pedersen; John J Kopchick; Vishwajeet Puri; Niels Jessen; Jens Otto L Jørgensen Journal: Mol Metab Date: 2019-08-20 Impact factor: 7.422