The Joint Annual Scientific Meetings of the Endocrine Society of Australia and the Society for Reproductive Biology 2018

Mechanisms controlling hormone secretion in human gut and its relevance to metabolism (#161)

Damien Keating 1
  1. College of Medicine and Public Health, Flinders University, Adelaide, South Australia, Australia

Gut endocrine cells (called enteroendocrine cells) are scattered amongst the gastrointestinal epithelium and collectively constitute the largest endocrine tissue in our body. They consist of an array of different cell types, each synthesising different peptide hormones. Many of these hormones have significant effects on metabolism, food intake and body weight. Our studies have focused on cells that release GLP-1, PYY and serotonin (5-HT). We have combined secretion studies using ex vivo tissue from human colon, ileum and duodenum with in vivo studies in lean, obese and type 2 diabetes individuals. Gut-derived 5-HT suppresses thermogenesis in mice and causes obesity. We have identified that gut-derived 5-HT increases in obese humans, and that gut 5-HT acts as a link between the gut microbiome and host obesity. GLP-1 is an incretin hormone and, along with PYY, can regulate central pathways associated with food intake. We have elucidated the pathway by which glucose triggers GLP-1 secretion in human small intestine and identified that the melanocortin pathway, typically associated with central pathways controlling food intake, also exists within the gut epithelium and activates GLP-1 and PYY secretion in human gut via the MC4 receptor. Identifying novel mechanisms controlling peripheral gut hormone secretion may have direct relevance to developing new approaches to regulating metabolism and obesity in humans.