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

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Abstract

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-γ) and chemoattractants (interferon-inducible T cell α-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.

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