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Growth Hormone Blunts Protein Oxidation and Promotes Protein Turnover to a Similar Extent in Abdominally Obese and Normal-Weight Women

Department of General Internal Medicine (M.M.B., M.F., A.E.M., H.P.), Department of Endocrinology (J.A.R.), and Centre for Human Drug Research (J.B., M.L.D.K., A.F.C.), Leiden University Medical Centre, 2300 RC Leiden, The Netherlands; and Center for Liver, Digestive and Metabolic Diseases, Laboratory of Paediatrics (F.S.), University Hospital Groningen, 9713 GZ Groningen, The Netherlands

Address all correspondence and requests for reprints to: M. M. Buijs, M.D., Department of General Internal Medicine, Leiden University Medical Centre, C1-R39, P.O. Box 9600, 2300 RC Leiden, The Netherlands. E-mail: m.m.buijs{at}lumc.nl.

Abstract

Abdominally obese individuals have reduced 24-h plasma GH concentrations. Their normal plasma IGF-I levels may reflect GH hypersensitivity. Alternatively, obesity-associated hyposomatotropism may cause less biological effect in target tissues. We therefore determined whole-body responsiveness to the anabolic effects of GH in abdominally obese (OB) and normal weight (NW) premenopausal women. A 1-h iv infusion of GH or placebo was randomly administered to six NW (body mass index, 21.1 ± 1.9 kg/m²) and six OB (body mass index, 35.5 ± 1.5 kg/m²) women in a cross-over design. Endogenous insulin, glucagon and GH secretion was suppressed by infusion of somatostatin. Whole-body protein turnover was measured using a 10-h infusion of [¹³C]-leucine. GH administration induced a similar plasma GH peak in NW and OB women (49.8 ± 10.4 vs. 45.1 ± 5.6 mU/liter). GH, compared with placebo infusion, increased nonoxidative leucine disposal, P < 0.0001) and endogenous leucine appearance (R_a, P = 0.0004) but decreased leucine oxidation (P = 0.0051). All changes were similar in both groups. Accordingly, whole-body GH responsiveness, defined as the maximum response of nonoxidative leucine disposal, leucine R_a, and oxidation per unit of GH, was not different in OB and NW women (0.25 ± 0.18 vs. 0.19 ± 0.17 µmol/kg·h, 0.21 ± 0.23 vs. 0.13 ± 0.17 µmol/kg·h, and -0.10 ± 0.08 vs. -0.08 ± 0.05 µmol/kg·h, respectively). These results indicated that whole-body tissue responsiveness to the net anabolic effect of GH is similar in OB and NW women. Hence, we inferred that hyposomatotropism may promote amino acid oxidation and blunt protein turnover in abdominal obesity. However, hyposomatotropism cannot account for all anomalous features of protein metabolism in abdominally obese humans.

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