ºÚÁÏÍø

Abstract

Background: Recent studies have demonstrated an association between gastrointestinal hormone release and the regulation of appetite and body weight. We found that the intestinal serotonergic system is involved in these processes. Hitherto, most data derive from animal experiments, whereas human data investigating gastrointestinal hormones are rare. Our study focuses on possible interactions between weight regulating hormones and the serotonergic system in obese and differences when compared to normal weight humans. Methods: Jejunalwhole tissue samples were collected from 164 obese (120 women; BMI (Mean ± SD): 43.5±6.6 kg/m2, Age: 41.5±12.9 years) that underwent Roux-en-Y gastric bypass and 18 normal weight patients (7 women; BMI (Mean ± SD): 23.5±3.0 kg/m2, Age: 71.6±10.9 years). mRNA expression of cholecystokinin (CCK), peptide YY3-36 (PYY), nesfatin-1, ghrelin, ghrelin O-acyl-transferase (GOAT), leptin, leptin receptor (leptinR), glucagon-like-peptide 1 receptor (GLP-1R), serotonin transporter (SERT), tryptophan hydroxylase 1 (TPH1) and serotonin receptor 3A (5-HT3AR) were measured with qRT-PCR. Protein expression of two tight junction molecules (zonula 1/2) was determined with western blot. Correlations were calculated using SSPS. Results: Positive bivariate correlationsof not only weight regulating but also serotonergic factors and tight junction proteins were determined in the obese. Similar correlations were found in normal weight patients; however significant differences for the receptors were detected. Comparing mRNA expression of the obese with normal weight patients, we found significant differences for CCK, nesfatin1, ghrelin, GOAT, leptinR as well as SERT and TPH1. Conclusion: For the first time it is shown the correlations between weight regulating, serotonergic factors and tight junctions in the intestine of obese and partly normal weight patients. Furthermore, a dysregulation of important weight regulating molecules seems to exist in the obese. Simulation of key weight regulating and serotonergic signals using combination therapies may be a promising strategy in controlling meal size and subsequent weight gain.

Biography