Mapping of Ghrelin Gene Expression and Cell Distribution in the Stomach of Morbidly Obese Patients-a Possible Guide for Efficient Sleeve Gastrectomy Construction

Ghrelin is secreted mainly in the stomach and plays a role in food intake regulation. Morbidly obese (MO) individuals report a decline in appetite after sleeve gastrectomy (SG), presumably due, in part, to ghrelin cell removal. Ghrelin cell distribution and expression were determined in three areas of resected stomach specimens from MO patients subjected to SG. Resected stomach specimens from 20 MO patients undergoing SG were analyzed. Real-time polymerase chain reaction of ghrelin mRNA and immunohistostaining for ghrelin cells in three stomach regions (fundus, body, and pre-antral areas) were performed. Body mass index (BMI) and total plasma ghrelin levels were obtained before and 3 months postoperatively. Ghrelin mRNA was detected throughout the stomach, its expression decreasing from the fundus towards the antrum. The relative quantification for ghrelin mRNA expression was 0.043, 0.026, and 0.015 at the fundus, body, and pre-antral region, respectively (P = 0.05, fundus vs. pre-antral region). Average ghrelin cell counts declined from 60 +/- 40 to 45 +/- 20 and 39 +/- 13 cells/high power fields in the fundus, body, and pre-antral region, respectively. Three months after surgery, total plasma ghrelin levels decreased from 1,676 +/- 470 to 1,179 +/- 188 pg/ml (P < 0.00001) and BMI dropped from 46 +/- 6 to 38 +/- 5 kg/m(2) (P < 0.00001). Distribution and expression of ghrelin-secreting cells throughout the stomach were defined, emphasizing the importance of meticulous resection of the fundus during SG for maximal ghrelin cell removal.