The Short-Term Impact of Roux-en-Y Gastric Bypass on Enteroendocrine Hormone Distribution and Density in Rhesus Macaques

Abstract

Abstract Roux-en-Y gastric bypass (RYGB) surgery results in profound weight loss and improvements in glucose homeostasis through a likely combination of malabsorption and changes in GI tract signaling. One component of GI tract signaling implicated in RYGB effects are enteroendocrine hormones, which are produced along the tract and regulate GI tract motility, pancreas exocrine and endocrine functions, including insulin release, and central nervous system control of feeding. While RYGB has been shown to cause post-prandial serum increases of several enteroendocrine hormones, the mechanism for how this occurs in the GI tract is still unknown. The current study examined GI tract tissue 13 weeks after RYGB or sham-surgery combined with pair-feeding (Sham/PF) in adult rhesus macaques. In situ hybridization analysis revealed no RYGB-induced changes compared to Sham/PF animals in the overall distribution of enteroendocrine hormones, with cholecystokinin (CCK) and glucose-dependent insulinotropic peptide (GIP) cells found predominantly in the proximal small intestine and preglucagon, encoding glucagon-like peptide-1 (GLP-1), and peptide tyrosine tyrosine (PYY) cells found predominantly in the ileum and colon. Immunohistochemistry was performed to further characterize the impact of RYGB on enteroendocrine cell density. No differences were observed in CCK cell densities in the proximal tract following RYGB, nor were there any differences in PYY and GLP-1 densities in the distal intestine. The only observed difference was an increase in serotonin and chromogranin A cell densities in the ileum of the RYGB group compared to the Sham/PF group. Serotonin has diverse actions from regulating GI tract motility to central nervous system signaling via the vagus nerve. Additional studies are planned to investigate how this up-regulation of serotonin may impact metabolic physiology after RYGB.