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Adipokine Protein Expression Pattern in Growth Hormone Deficiency Predisposes to the Increased Fat Cell Size and the Whole Body Metabolic Derangements

Jozef Ukropec, Adela Penesová, Martina kopková, Mikulá Pura, Miroslav Vlek, ofia Rádiková, Richard Imrich, Barbara Ukropcová, Mária Tajtáková, Juraj Koka, tefan Zórad, Vítazoslav Belan, Peter Vauga, Juraj Payer, Juergen Eckel, Iwar Klime and Daniela Gaperíková

Institute of Experimental Endocrinology (J.U., A.P., M.S., M.V., Z.R., R.I., B.U., J.K., S.Z., I.K., D.G.), Slovak Academy of Sciences, 833 06 Bratislava, Slovakia; National Institute of Endocrinology and Diabetology (M.P., P.V.), 034 91 L’ubocha, Slovak Republic; The First Clinic of Internal Medicine (M.T.), P. J. afárik University, 041 80 Koice, Slovak Republic; Radiodiagnostic Clinic (V.B.) and The Fifth Clinic of Internal Medicine (J.P.), Comenius University School of Medicine, 811 08 Bratislava, Slovakia; and German Diabetes Center (J.E.), 40225 Düsseldorf, Germany

Address all correspondence and requests for reprints to: Jozef Ukropec, Ph.D., Diabetes Laboratory, Institute of Experimental Endocrinology, Centre of Excellence acknowledged by European Commission, Slovak Academy of Sciences, Vlárska 3, 833 06 Bratislava, Slovak Republic. E-mail: jozef.ukropec{at}savba.sk (http://www.endo.sav.sk/d-ldn.htm).

Context: GH deficiency (GHD) in adults is associated with central adiposity, dyslipidemia, and insulin resistance.

Objective: The objective of the study was to test the hypothesis that GHD might change the spectrum of adipokines and thus influence the adipose tissue and the whole-body metabolic and inflammatory status leading to development of insulin resistance.

Design: This was a single-center observational study with a cross-sectional design.

Participants and Methods: Protein arrays were used to characterize adipokines expressed in the sc adipose tissue obtained from young GHD adults and compared with age-, gender-, and body mass index (BMI)-matched group of healthy individuals. All subjects underwent an oral glucose tolerance test, euglycemic hyperinsulinemic clamp, and magnetic resonance imaging examination.

Results: Presence of abdominal obesity, enlarged adipocytes, increased circulating high-sensitivity C-reactive protein, impaired glucose tolerance, and decreased insulin action were found in GHD. Changes in adipokine protein expression due to GHD were highly dependent on the obesity phenotype. Lean GHD individuals (BMI 23 kg/m²) had decreased protein levels for stem cell factor and epithelial growth factor, indicating a possible defect in adipocyte differentiation and proliferation. Decrease of vascular endothelial growth factor, stromal cell-derived factor, angiopoietin-2, and brain-derived neurotrophic factor advocated for attenuated angiogenesis and neurogenesis. Presence of obesity (BMI 31 kg/m²) eliminated these inhibitory effects. However, adipose tissue expansion in GHD individuals was paralleled by an elevation of adipose tissue proinflammatory cytokines (IL-1β, interferon-) and chemoattractants (interferon-inducible T cell -chemoattractant, monocyte chemotactic protein-2, monocyte chemotactic protein-3, eotaxin).

Conclusion: Our data demonstrate that GHD modulates adipokine and cytokine protein expression pattern, which might influence the adipose tissue growth and differentiation and predispose to tissue hypoxia, inflammation, and a defect in the whole-body insulin action.