Obestatin is not elevated or correlated with insulin in children with Prader-Willi syndrome.

CONTEXT: Obestatin is a peptide hormone derived from the proteolytic cleavage of ghrelin preprohormone. In Prader-Willi syndrome (PWS), the levels of total ghrelin (TG) and acylated ghrelin (AG) are increased, and these hormones are regulated by insulin. OBJECTIVE: Our objective was to analyze the changes in the obestatin levels after glucose loading and to characterize the correlations of obestatin with TG, AG, and insulin. DESIGN: Plasma obestatin, TG, AG, and insulin levels were measured in PWS children (n = 15) and controls (n = 18) during an oral glucose tolerance test. SETTING: All subjects were admitted to the Samsung Medical Center. INTERVENTIONS: An oral glucose tolerance test was performed after an overnight fast. MAIN OUTCOME MEASURES: The plasma levels of obestatin, TG, AG, and serum insulin were measured at 0, 30, 60, 90, and 120 min after glucose challenge, and areas under the curves (AUCs) were calculated. RESULTS: No significant difference in AUC of the plasma obestatin was found between the PWS children and normal obese controls (P = 0.885), although AUC of AG (P = 0.002) and TG (P = 0.003) were increased in the PWS children. Moreover, There was a negative correlation between the AUC of AG and AUC of insulin both in PWS (r = -0.432; P = 0.049) and in controls (r = -0.507; P = 0.016). However, AUC of obestatin was not significantly correlated with AUC of insulin (in PWS, r = 0.168 and P = 0.275; in controls, r = -0.331 and P = 0.09). CONCLUSIONS: Our results indicate that plasma obestatin is not elevated in PWS children and is not regulated by insulin both in PWS children and in obese controls.

Suppression of acylated ghrelin during oral glucose tolerance test is correlated with whole-body insulin sensitivity in children with Prader-Willi syndrome.

CONTEXT: Decreased fasting ghrelin levels and decreased ghrelin suppression in overweight children have been reported to be associated with insulin resistance. However, Prader-Willi syndrome (PWS) is associated with increased total ghrelin levels and relative hypoinsulinemia. OBJECTIVE: The objective of the study was to analyze changes in acylated ghrelin (AG) and des-acylated ghrelin (DAG) levels after glucose loading and characterize correlations between insulin sensitivity and ghrelin suppression. DESIGN: Plasma glucose, insulin, AG, and DAG levels were measured in PWS children (n = 11) and normal obese controls (n = 10) during oral glucose tolerance testing. SETTING: All subjects were admitted to the Samsung Medical Center. INTERVENTIONS: Oral glucose tolerance testing was performed in all subjects after an overnight fast. MAIN OUTCOME MEASURES: Plasma levels of the hormones AG, DAG, and insulin, and those of glucose at 0, 30, 60, 90, and 120 min after glucose challenge were measured, and whole-body insulin sensitivity index (WBISI) values were calculated. RESULTS: AG levels fell markedly more from fasting levels in PWS children than normal healthy obese controls at 30, 60, and 90 min after glucose challenge, but no significant differences in DAG levels were observed at any time between PWS patients and controls. Fasting AG and DAG levels were found to correlate with WBISI in PWS, and absolute suppressions (Delta from baseline) in AG at 30 min after glucose challenge (nadir) were also correlated with WBISI in PWS (r = 0.64, P = 0.035). CONCLUSIONS: Our results suggest that AG is sensitively suppressed by insulin and that this suppression correlated with insulin sensitivity in PWS children.

Increased density of ghrelin-expressing cells in the gastric fundus and body in Prader-Willi syndrome.

CONTEXT: The levels of ghrelin, an orexigenic hormone secreted by oxyntic cells in the digestive tract, are elevated in Prader-Willi syndrome (PWS) and GH deficiency (GHD) patients. In this study, we hypothesized that the hyperghrelinemia observed in PWS is related to IGF-I or GH/IGF axis deficiency. DESIGN: We investigated the densities of ghrelin-expressing cells (GECs), the amounts of ghrelin in gastric tissues, and ghrelin levels in plasma in 16 PWS patients and compared these results with those of 13 GHD patients and comparison groups (19 normal lean and 10 normal obese subjects). RESULTS: In the gastric body and fundus, 2- to 3-fold increases in the numbers of GECs (P < 0.001) and in the amounts of ghrelin (P < 0.018) were noted in PWS patients vs. comparison groups, whereas GEC numbers in GHD patients were similar to those of the comparison group despite elevated fasting plasma ghrelin levels. In addition, IGF-I sd scores in PWS were not found to be correlated with GEC densities, the amounts of ghrelin expressed in gastric tissues, or plasma ghrelin levels. CONCLUSIONS: Our results suggest that IGF-I or GH/IGF axis deficiency appears to be unrelated to observed GEC increases in the stomach of patients with PWS.

Hyperghrelinemia does not accelerate gastric emptying in Prader-Willi syndrome patients.

Prader-Willi syndrome (PWS) is the most common form of syndromic obesity associated with hyperphagia. Because ghrelin stimulates gastric motility in rodents, and PWS patients have 3- to 4-fold higher fasting plasma ghrelin concentrations than normal subjects, we hypothesized that hyperphagia associated with PWS may be partly explained by rapid gastric emptying due to the increased gastric motility caused by ghrelin. We determined gastric emptying times (GETs) and measured ghrelin levels in 11 PWS children and 11 age-, sex-, and body mass index-matched controls using a standard meal containing [(99m)Tc]diaminetriaminepentacetate. Median plasma ghrelin levels before (precibum) and after the GET study were higher in PWS patients than in controls (P = 0.004 and P = 0.001, respectively). Median percent gastric retentions at 90 min after the standard meal were 57.1% (range, 34.0-83.2%) in PWS patients and 40.2% (range, 27.2-60.2%) in controls (P = 0.03). In particular, precibum ghrelin concentrations were not significantly correlated with the rate of gastric emptying in PWS patients (P = 0.153; r = 0.461) or controls (P = 0.911; r = 0.048). Our results show that gastric emptying in PWS is reduced despite higher ghrelin levels, and that the voracious appetite associated with PWS is related to another mechanism.