Hyperghrelinemia Does Not Accelerate Gastric Emptying in Prader-Willi Syndrome Patients

Abstract

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.

Delayed Gastric Emptying in Patients with Prader Willi Syndrome

“…Our results confirm the findings of Choe et al, who performed scinitigraphic gastric emptying studies with a standard meal of solid food in eleven children with PWS 10 . Another recent study found gastric emptying times in PWS similar to lean healthy controls but significantly increased compared to obese controls 11 .…”

“…In PWS a disturbance of hypothalamic regulation (1) seems to be causal for a reduced parasympathic activity, leading to impaired temperature regulation and production of saliva. Furthermore patients with PWS usually can not vomit 1,10 .…”

Eating Behavior and Gastric Emptying in Adults with Prader-Willi Syndrome

“…Although our adult PWS patients were obese (median BMI 34.9), our results are in accordance with the results in a recent study by Choe et al [9] of PWS children with normal BMI (median 22.2). Choe et al [9] assessed gastric emptying rate using the scintigrafic technique, but the two methods have been found to be comparable [14] . Bonazzi et al [20] have recently reported that treatment of patients with simple obesity with an intragastric balloon decreases the rate of gastric emptying and reduces weight.…”

Ghrelin Gene Products and the Regulation of Food Intake and Gut Motility

“…Taken together, these couple acyl ghrelin with orexigenic, gastroprokinetic, and hedonic-rewarding effects. Solid meal gastric emptying in children with Prader-Willi syndrome was delayed (Choe et al, 2005) and non-nutrient liquid gastric emptying in adults with Prader-Willi syndrome was normal (Hoybye et al, 2007), despite higher acyl ghrelin levels, suggesting that the voracious appetite associated with Prader-Willi syndrome could be something other than the gastric emptying mechanism. Regarding colonic motility, intracerebroventricular and intraperitoneal injection of acyl ghrelin decreased colonic transit time in conscious fed rats, which was blocked by pretreatment with intracerebroventricular Y 1 receptor antagonist, but not Y 2 receptor antagonist (Tebbe et al, 2005b).…”