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Original Article |
Division of Endocrinology, Department of Pediatrics (A.M.H., S.H.L., R.G.R., K.L.P.) and Division of Endocrinology, Diabetes, and Clinical Nutrition, Department of Medicine (D.D.S., J.Q.P.), Oregon Health and Science University, Portland, Oregon 97201; and University Department of Medicine (I.S.F., S.O.), Addenbrooke’s Hospital, Cambridge, United Kingdom
Address all correspondence and requests for reprints to: Andrea M. Haqq, M.D., Duke University Medical Center, Department of Pediatrics, Division of Endocrinology and Diabetes, DUMC 3080, 306FA Bell Building, Durham, North Carolina 27710. E-mail: haqq0001{at}mc.duke.edu.
Ghrelin, an endogenous ligand of the GH secretagogue receptor, stimulates appetite and causes obesity in animal models and in humans when given in pharmacologic doses. Prader-Willi Syndrome (PWS) is a genetic obesity syndrome characterized by GH deficiency and the onset of a voracious appetite and obesity in childhood. We, therefore, hypothesized that ghrelin levels may play a role in the expression of obesity in this syndrome. We measured fasting serum ghrelin levels in 13 PWS children with an average age of 9.5 yr (range, 5–15) and body mass index (BMI) of 31.3 kg/m2 (range, 22–46). The PWS group was compared with 4 control groups: 20 normal weight controls matched for age and sex, 17 obese children (OC), and 14 children with melanocortin-4 receptor mutations (MC4) matched for age, sex, and BMI, and a group of 3 children with leptin deficiency (OB). In non-PWS subjects, ghrelin levels were inversely correlated with age (r = 0.36, P = 0.007), insulin (r = 0.55, P < 0.001), and BMI (r = 0.62, P < 0.001), but not leptin. In children with PWS, fasting ghrelin concentrations were not significantly different compared with normal weight controls (mean ± SD; 429 ± 374 vs. 270 ± 102 pmol/liter; P = 0.14). However, children with PWS did demonstrate higher fasting ghrelin concentrations (3- to 4-fold elevation) compared with all obese groups (OC, MC4, OB) (mean ± SD; 429 ± 374 vs. 139 ± 70 pmol/liter; P < 0.001). In conclusion, ghrelin levels in children with PWS are significantly elevated (3- to 4-fold) compared with BMI-matched obese controls (OC, MC4, OB). Elevation of serum ghrelin levels to the degree documented in this study may play a role as an orexigenic factor driving the insatiable appetite and obesity found in PWS.
This study was conducted through the Oregon Health and Science University General Clinical Research Center (M01-RR-00334) and was supported by a grant from Pharmacia, Inc. (A.M.H., S.H.L., and R.G.R.) and by the NIH Grant K-23-DK-02689 (to J.Q.P.).
Abbreviations: AGRP, Agouti-related protein; BMI, body mass index; CV, coefficients of variation; MC4, melanocortin-4; MC4-R, MC4 receptor; NC, normal weight children; NPY, neuropeptide Y; OB, children with leptin deficiency; OC, obese children; PWS, Prader-Willi Syndrome.
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