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Elevated Fasting Plasma Ghrelin in Prader-Willi Syndrome Adults Is Not Solely Explained by Their Reduced Visceral Adiposity and Insulin Resistance

Department of Endocrinology (A.P.G., A.B.G., M.K.), North East Thames Radio-immunoassay Laboratory (G.C., R.E.), St. Bartholomew’s Hospital, London, United Kingdom EC1A 7BE; Departments of Metabolic Medicine (A.P.G., M.A.G., S.R.B.) and Dietetics (A.E.B., G.F.), Robert Steiner Magnetic Resonance Imaging Unit (E.L.T., J.D.B.), Medical Research Council Clinical Sciences Center, Imperial College School of Medicine, Hammersmith Hospital, London, United Kingdom W12 0NN; and Section of Developmental Psychiatry, University of Cambridge (A.J.H.), Cambridge, United Kingdom CB2 2AH

Address all correspondence and requests for reprints to: Dr. A. P. Goldstone, Division of Pediatric Genetics, Box 100296, University of Florida College of Medicine, Gainesville, Florida 32610-0296. E-mail: tgoldstone{at}yahoo.com.

Plasma ghrelin is elevated in Prader-Willi syndrome (PWS). This might contribute to obesity or GH deficiency in such patients. Visceral adiposity and insulin resistance are reduced in PWS, which might lead to hyperghrelinemia. We measured fasting plasma ghrelin in control female (n = 39), PWS female (n = 12), and PWS male (n = 6) adults. In controls and PWS, ghrelin was negatively correlated with visceral adiposity, fasting insulin, and homeostasis model insulin resistance index. There was no significant correlation with serum IGF-I in PWS. In stepwise linear regression, visceral adiposity (P < 0.02) had a stronger inverse correlation with ghrelin than sc fat depots in controls and PWS, possibly through hyperinsulinemia, as the correlations with insulin resistance were even stronger (P < 0.01). PWS females had significantly (P < 0.001) elevated ghrelin (mean ± SD, 661 ± 360 pg/ml), compared with both nonobese (363 ± 163) and obese (191 ± 66) controls. Ghrelin was increased 3.4- to 3.6-fold in PWS females adjusting for total adiposity, 3.2- to 3.4-fold adjusting for visceral adiposity, and 3.0-fold adjusting for insulin resistance. Fasting plasma glucagon-like peptide-1 was normal in PWS females. The hyperghrelinemia in PWS adults is therefore not solely explained by their reduced visceral adiposity and relative hypoinsulinemia. Its cause and consequences await further elucidation.

This work was supported by the United Kingdom Medical Research Council and Marconi Medical Systems.

Abbreviations: AGRP, Agouti-related protein; ASCAT, abdominal sc adipose tissue; AT, adipose tissue; BMI, body mass index; FFM, fat-free mass; FM, fat mass; GHS-R, GH secretagogue receptor; GLP-1, glucagon-like peptide-1; HOMA-IR, homeostasis model insulin resistance index; HRT, hormone replacement therapy; INF, infundibular nucleus; MRI, magnetic resonance imaging; NPY, neuropeptide Y; OCP, oral contraceptive pill; POMC, proopiomelanocortin; PVN, paraventricular nucleus; PWS, Prader-Willi syndrome; SCAT, total sc adipose tissue; VAT, visceral adipose tissue.

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