Serum ghrelin levels are inversely correlated with body mass index, age, and insulin concentrations in normal children and are markedly increased in Prader-Willi syndrome.
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.
Haqq
Andrea M
AM
Division of Endocrinology, Department of Pediatrics, Oregon Health and Science University, Portland, Oregon 97201, USA. haqq0001@mc.duke.edu
Farooqi
I Sadaf
IS
O'Rahilly
Stephen
S
Stadler
Diane D
DD
Rosenfeld
Ron G
RG
Pratt
Katherine L
KL
LaFranchi
Stephen H
SH
Purnell
Jonathan Q
JQ
D000293:Adolescent; D000375:Aging / Q000097:blood*; D015992:Body Mass Index; D002648:Child; D002675:Child, Preschool; D005260:Female; D054439:Ghrelin; D006801:Humans; D007328:Insulin / Q000097:blood*; D008297:Male; D009765:Obesity / Q000097:blood; D009994:Osmolar Concentration; D036361:Peptide Hormones / Q000097:blood*; D011218:Prader-Willi Syndrome / Q000097:blood*; D012016:Reference Values
D054439:Ghrelin; D007328:Insulin; D036361:Peptide Hormones