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Reduction of Free Fatty Acids By Acipimox Enhances the Growth Hormone (GH) Responses to GH-Releasing Peptide 2 in Elderly Men

Departments of Clinical Endocrinology (P.S.v.D., H.P.F.K.) and Medical Physiology and Sports Medicine (H.E.C.S., W.R.d.V., M.N., E.B., E.J.W.), University Medical Center, 3508 GA Utrecht, The Netherlands; and Departments of Physiology (C.D.) and Medicine (F.F.C.), Santiago de Compostela University, 15700 Santiago de Compostela, Spain

Address correspondence and requests for reprints to: P. S. van Dam, M.D., Ph.D., Department of Clinical Endocrinology, University Medical Center L00.407, Postbus 85.500, 3508 GA Utrecht, The Netherlands. E-mail P.S.vanDam{at}digd.azu.nl

GH release is increased by reducing circulating free fatty acids (FFAs). Aging is associated with decreased plasma GH concentrations. We evaluated GH releasing capacity in nine healthy elderly men after administration of GH-releasing peptide 2 (GHRP-2), with or without pretreatment with the antilipolytic drug acipimox, and compared the GHRP-2-induced GH release with the response to GHRH. The area under the curve (AUC) of the GH response after GHRP-2 alone was 4.8 times higher compared with GHRH alone (1834 ± 255 vs. 382 ± 78 µg/L·60 min, P < 0.001). Acipimox, which reduced FFAs from 607 µmol/L to 180 µmol/L, increased the GH AUC to 1087 after GHRH and to 2956 µg/L·60 min after GHRP-2 (P < 0.01). The AUC after acipimox/GHRP-2 were positively correlated with the AUC after GHRP-2 alone (r = 0.93, P < 0.01); this was also observed between acipimox/GHRH and GHRH alone (r = 0.73, P = 0.03). Significant negative correlations were observed between basal FFAs and AUC after GHRH or GHRP-2 after combining the data with and without acipimox (r = 0.58, P = 0.01 and r = 0.48, P = 0.04, respectively), and between basal FFAs and GH at t = 0 (r = -0.44, P = 0.001). Interestingly, GHRP-2 administration was followed by a significant early rise in plasma FFAs by 60% (P = 0.01), indicating an acute lipolytic effect. In conclusion, reduction of circulating FFAs strongly enhances GHRP-2-stimulated GH release in elderly men. The data indicate that the decreased GH release associated with aging can be reversed by acipimox and that the pituitary GH secretory capacity in elderly men is still sufficient.

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