1214-P: Urocortin3 Is Overexpressed in GLP-1 Positive Enteroendocrine Cells in Human Obesity

UCN3 acts via CRHR2, increases pAKT, pCREB and promotes somatostatin (SST) secretion from D cells. It is unknown whether UCN3 is expressed in gastrointestinal mucosa and its role in obesity. We studied 34 participants, 17 normal weight (age 38±13, 59% female), and 17 with obesity (age 39±9, 65% female). Colonic biopsies were obtained. Single Cell-transcriptomics were completed using the Chromium 10X Genomics platform and Illumina HiSeq4000. Blood was collected at fasting and postprandial at 15, 45, and 90 minutes. RTqPCR and Immunofluorescence (IF) were used to detect UCN3. Blood GLP1 levels were determined by ELISA. HT29 cells were incubated with Sauvagine (2µM), a CRHR2 agonist, for 0, 10, 30, and 60 mins. Cells and supernatant were harvested to perform RTqPCR for SST and CRHR2, western blot for pAKT and pCREB, and ELISA for SST. scRNA-Seq library revealed expression of UCN3 in GLP1 positive cells, confirmed by IF. Ileum and colonic UCN3 mRNA expression was significantly higher in obesity vs. lean (p Therefore, UCN3 is overexpressed in GLP1 positive cells in human obesity. UCN3 increases the secretion of SST, which may explain the association with lower postprandial GLP1. Disclosure M. Ricardo silgado: None. A. Acosta: n/a. C. Yun: None. A. Mcrae: None. G. Calderon: None. G. Daniel: None. C. Alejandro: None. L. Cifuentes: None. A. Hashem: None. M. D. Hurtado: n/a.