Meal suppression of circulating ghrelin is normalized in obese individuals following gastric bypass surgery

Objective: It has been proposed that the success of maintained weight loss in morbidly obese subjects following Roux-en-Y gastric bypass (RYGBP) surgery depends on inappropriately low circulating concentrations of the appetite-stimulating peptide ghrelin, being unresponsive to food intake. In this study, this hypothesis was examined. Design: Cross-sectional study with repeated blood samples in 40 subjects after 14 h of prolonged overnight fasting followed by a standardized mixed meal ( 770 kcal). Subjects: Twenty men and 20 women were included: 10 middle-aged morbidly obese ( body mass index (BMI) 43.9 +/- 3.3 kg/m(2)), 10 middle-aged subjects who had undergone RYGBP at the Uppsala University Hospital (BMI 34.7 +/- 5.8 kg/m(2)), 10 middle-aged non- obese ( BMI 23.5 +/- 2.2 kg/m(2)) and 10 young non- obese ( BMI 22.7 +/- 1.8 kg/m(2)). Measurements: Ghrelin, glucose and insulin levels were analysed pre- and postprandially. Results: In the morbidly obese, ghrelin concentrations were lower in the morning than in the RYGBP group and did not change following the meal. In the RYGBP group, fasting ghrelin levels fell after meal intake and showed similar suppression as both age-matched and young non- obese controls. The RYGBP surgery resulted in an increased meal-induced insulin secretion, which was related to the degree of postprandial ghrelin suppression. Conclusion: The present study demonstrates low circulating concentrations of ghrelin and blunted responses to fast and feeding in morbidly obese subjects. Marked weight reduction after RYGBP at our hospital is followed by a normalization of ghrelin secretion, illustrated by increased fasting levels compared to the preoperative obese state and regain of meal-induced ghrelin suppression.