Role of DPP-4 and NPY Family Peptides in Gastrointestinal Symptoms Associated with Obesity and Type 2 Diabetes Mellitus

<i>Background and Objectives</i>: Neuropeptide Y (NPY) family peptides and dipeptidyl peptidase-4 (DPP-4) are involved in gastrointestinal regulation and may contribute to obesity and type 2 diabetes mellitus (T2DM) pathophysiology. This study investigates their expression in jejunal muscular tissue and associations with gastrointestinal symptoms in patients with obesity, with (OB+/DM+) and without T2DM (OB+/DM-). <i>Materials and Methods</i>: This cross-sectional study includes forty-four patients undergoing laparoscopic Roux-en-Y gastric bypass divided based on T2DM status. Gastrointestinal symptoms were assessed using the Gastrointestinal Symptom Rating Scale (GSRS) questionnaire, and jejunal tissue samples were analyzed for DPP-4, NPY, peptide YY (PYY), and pancreatic polypeptide (PP) mRNA and protein levels. <i>Results</i>: DPP-4, NPY, PYY, and PP gene expression in jejunal muscular tissue was similar between groups. In the OB+/DM+ group, PP protein was higher, while DPP-4 and PYY were lower compared to the OB+/DM- group. Significant positive correlations between DPP-4 and NPY, PYY, and PP were found in the OB+/DM- group, while only DPP-4 and PYY correlated in the OB+/DM+ group. Gastrointestinal symptoms in the OB+/DM- group showed positive correlations with PP (abdominal pain), DPP-4 (indigestion), and NPY (constipation). <i>Conclusions</i>: The study demonstrates significant differences in DPP-4, PYY, and PP protein expression between patients with obesity, with or without T2DM. Peptide correlations with gastrointestinal symptoms in non-diabetic patients suggest distinct regulatory mechanisms, warranting further research.