Obesity Does Not Increase Effects of Synthetic Ghrelin on Human Gastric Motor Functions

Background & Aims: Ghrelin is secreted by the stomach and stimulates food intake. Obese individuals have lower fasting plasma ghrelin levels but increased appetite, suggesting greater responses to endogenous ghrelin in obesity. The aim of this study was to compare effects of exogenous ghrelin (at a dose that stimulates growth hormone [GH] release in the physiologic range) versus placebo on gastric emptying, gastric volume, and postprandial symptoms and determine whether body mass (ranging from normal weight to obesity) influences responses to ghrelin. Methods: After intravenous bolus synthetic human ghrelin (0.33 μg/kg) or saline, we measured plasma GH, gastric volume, and gastric emptying by combined ^99mTc-single-photon emission computed tomography and scintigraphy (¹¹¹In egg meal, 300 kcal) and postprandial symptoms using visual analogue scales. Results: In 25 obese subjects (5 men and 20 women; body mass index [BMI], 36 ± 4 kg/m²) and 13 female normal-weight (BMI, 22 ± 2 kg/m²) subjects of similar ages, ghrelin increased GH levels (15.0 ± 2.4 ng/mL) at 40 minutes postinjection and tended to decrease fasting gastric volumes compared with placebo (P = .059). There were no effects of BMI on treatment response and no differences between ghrelin and saline on postprandial (P = .09) or change in (postprandial minus fasting) gastric volumes, gastric emptying, or aggregate postprandial symptoms. Effects of ghrelin did not differ between obese and normal-weight participants. Conclusions: At doses that stimulate physiologic GH plasma levels, synthetic ghrelin tended to decrease fasting gastric volumes without altering postprandial volumes or gastric emptying in a predominantly female cohort. The data are not consistent with the hypothesis that higher body mass is associated with increased gastric responsiveness to ghrelin.