دورية أكاديمية
Growth hormone signaling in muscle and adipose tissue of obese human subjects: associations with measures of body composition and interaction with resveratrol treatment.
| العنوان: | Growth hormone signaling in muscle and adipose tissue of obese human subjects: associations with measures of body composition and interaction with resveratrol treatment. |
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| المؤلفون: | Clasen BF; 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., Poulsen MM, Escande C, Pedersen SB, Møller N, Chini EN, Jessen N, Jørgensen JO |
| المصدر: | The Journal of clinical endocrinology and metabolism [J Clin Endocrinol Metab] 2014 Dec; Vol. 99 (12), pp. E2565-73. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Oxford University Press Country of Publication: United States NLM ID: 0375362 Publication Model: Print Cited Medium: Internet ISSN: 1945-7197 (Electronic) Linking ISSN: 0021972X NLM ISO Abbreviation: J Clin Endocrinol Metab Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2017- : New York : Oxford University Press Original Publication: Springfield, Ill. : Charles C. Thomas |
| مواضيع طبية MeSH: | Adipose Tissue/*metabolism , Antioxidants/*pharmacology , Body Composition/*physiology , Human Growth Hormone/*physiology , Muscles/*metabolism , Obesity/*metabolism , Signal Transduction/*drug effects , Stilbenes/*pharmacology, 3T3-L1 Cells ; Adipose Tissue/drug effects ; Animals ; Body Composition/drug effects ; Double-Blind Method ; Mice ; Muscles/drug effects ; Obesity/physiopathology ; Resveratrol ; STAT5 Transcription Factor/metabolism ; Sirtuin 1/pharmacology |
| مستخلص: | 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. |
| سلسلة جزيئية: | ClinicalTrials.gov NCT01150955 |
| المشرفين على المادة: | 0 (Antioxidants) 0 (STAT5 Transcription Factor) 0 (STAT5B protein, human) 0 (Stilbenes) 12629-01-5 (Human Growth Hormone) EC 3.5.1.- (SIRT1 protein, human) EC 3.5.1.- (Sirtuin 1) Q369O8926L (Resveratrol) |
| تواريخ الأحداث: | Date Created: 20140723 Date Completed: 20151007 Latest Revision: 20181202 |
| رمز التحديث: | 20221213 |
| DOI: | 10.1210/jc.2014-2215 |
| PMID: | 25050904 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1945-7197 |
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| DOI: | 10.1210/jc.2014-2215 |