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Altered Neuroregulation of GH Secretion in Viscerally Obese Premenopausal Women

Department of General Internal Medicine (H.P., J.G.L., M.F., A.E.M.), and Center for Human Drug Research (J.B., A.F.C.), Leiden University Medical Center, 2300 RC Leiden, The Netherlands; and Division of Endocrinology (J.D.V.), Department of Internal Medicine, General Clinical Research Center and Center for Biomathematical Technology, University of Virginia Medical School, Charlottesville, Virginia 22908

Address all correspondence and requests for reprints to: H. Pijl, M.D., Ph.D., Department of General Internal Medicine, Leiden University Medical Center, C1-R39, P.O. Box 9600, 2300 RC Leiden, The Netherlands. E-mail: h.pijl{at}lumc.nl

Abstract

We used deconvolution analysis of 24-h plasma GH concentration profiles (10- min sampling intervals) to appraise GH secretion rates and elimination kinetics in obese (body mass index, 34 kg/m²) premenopausal women with large visceral fat area (LVFA; n = 8) vs. small visceral fat area (SVFA; n = 8) as determined by magnetic resonance imaging. The subjects were matched for body mass index, body fat percentage, and age. The impact of the loss of 50% of prestudy weight excess induced by caloric restriction was assessed as well. The results were compared with those obtained in normal weight control women (n = 8). LVFA subjects manifested markedly (4-fold) reduced mean plasma GH levels, which was brought about by jointly diminished basal and pulsatile GH secretion. Moreover, visceral obesity was associated with loss of regularity of GH release, as established by the approximate entropy statistic. In contrast, SVFA subjects produced normal daily amounts of GH and exhibited mean 24-h plasma GH concentrations that were similar to those in normal weight controls. GH half-life and distribution volume were not different among the study groups. Importantly, weight loss did not affect the daily GH secretion rate in LVFA women, so that their mean plasma GH concentration remained considerably reduced (50%) compared with controls (despite the loss of 40% of visceral fat). Normal GH kinetics in SVFA women were not significantly influenced by weight reduction. Thus, GH neuroregulation appears to be particularly altered in obese women with a tendency to store fat in their visceral adipose depot. Because weight loss did not reverse GH secretion rate in viscerally obese women, we speculate that relative hyposomatotropism is a primary feature of these women, which could be involved in their tendency to preferentially store excess fat in visceral adipose tissue.

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