Title : Anatomy of human gastric ghrelin cells in normal and obese patients
Abstract:
Ghrelin is a hormone produced in the gastrointestinal tract mainly by gastric gland cells with central and peripheral effects. The endocrine cells that produce it are mainly located in the gastric fundus. Their distribution in obese subjects is controversial. In this study we examined gastric samples from the fundus of stomachs removed by sleeve gastrectomy in 49 obese subjects. In each sample we quantified the presence of ghrelin cells (GPCs) by immunohistochemistry with a specific antibody and verified their relative amount compared to general endocrine population revealed by chromogranin immunoreactive cells (CPCs). The density of a specific endocrine cell in the general endocrine population (expressing chromogranin) has been considered as the more reliable method of analysis. Data were compared with those of 13 lean subjects evaluated by gastroscopy for various diagnostic suspects and resulting negative for any gastric disease. The obese subjects were also divided into three groups: normoglycemic (OB-Normoglic), hyperglycemic (OB-Hyperglyc) and diabetic (OB-Diab). In 44 cases (11 controls and 33 obese patients) a gene expression analysis of ghrelin and its functional enzyme ghrelin O-acyl transferase (GOAT) was performed. In 21 cases (4 controls and 17 obese patients), the protein levels of unacylated and acylated-ghrelin were measured by ELISA tests. In samples selected on the basis of gene expression (4 controls and 14 obese patients), the ultrastructure of ghrelin producing cells was also evaluated. Measuring the GPC density (GPCs/CPCs), we did not observe any difference between obese and lean patients. Comparative statistical analysis between groups did not find significant differences in ghrelin cell density (CTRL: 26.63 +/- 3.59, OB-Normoglic: 36.54 +/- 3.87, OB-Hyperglyc: 27.65 +/- 4.08, OB-Diab: 39.1 +/- 4.91) even when the obese group was divided into subgroups and compared with lean controls. Interglandular smooth muscle fibres were increased in obese patients. In line with a positive trend of the desacylated form found by ELISA, ghrelin and GOAT mRNAs in obese patients were significantly increased. When considering the three groups, gene expression was significantly different only for the OB-Hperglyc group (p = 0.02). The ghrelin cell ultrastructure, which is characteristic and allows it to be distinguished from other endocrine cells, is maintained even in obese subjects. In the hyperglycemic obese group, with high levels of gene expression of the hormone, the cells, while maintaining the general characteristics, showed clear signs of endocrine hyperactivity. A positive correlation between ghrelin gene expression and glycemic values, body mass index and GOAT was also found. All obese patients with type 2 diabetes recovered from diabetes at follow-up after 5 months with a 16.5% of weight loss. Given the known anti-insulin action of ghrelin, data suggest a possible role for gastric ghrelin in the complex architecture that takes part in the pathogenesis of type-2 diabetes.
Audience Take Away:
- Our data are only preliminary results which could open new frontiers in the field of medicine, with references to anatomists and endocrinologists
- The results I presented could bring together the work that researchers are carrying out around the world on several topics regarding different aspects obesity, diabetes or dysregulation of secreting cells in the stomach
- This research could be used by the audience as a clear starting point for more in-depth research regarding the metabolic improvement obtained in type-2 diabetic patients after sleeve-gastrectomy and could be a good lesson in endocrinology or cellular and molecular molecular biology
