A M Martin1, A L Lumsden1, R L Young2,3, C F Jessup3,4, N J Spencer1, D J Keating1,2. 1. Department of Human Physiology and Centre for Neuroscience, Flinders University, Adelaide, SA, Australia. 2. South Australian Health and Medical Research Institute (SAHMRI), Adelaide, SA, Australia. 3. Adelaide Medical School, University of Adelaide, Adelaide, SA, Australia. 4. Department of Anatomy and Histology and Centre for Neuroscience, Flinders University, Adelaide, SA, Australia.
Abstract
BACKGROUND: Enterochromaffin (EC) cells within the gastrointestinal (GI) tract provide almost all body serotonin (5-hydroxytryptamine [5-HT]). Peripheral 5-HT, released from EC cells lining the gut wall, serves diverse physiological roles. These include modulating GI motility, bone formation, hepatic gluconeogenesis, thermogenesis, insulin resistance, and regulation of fat mass. Enterochromaffin cells are nutrient sensors, but which nutrients they are responsive to and how this changes in different parts of the GI tract are poorly understood. METHODS: To accurately undertake such an examination, we undertook the first isolation and purification of primary mouse EC cells from both the duodenum and colon in the same animal. This allowed us to compare, in an internally controlled manner, regional differences in the expression of nutrient sensors in EC cells using real-time PCR. KEY RESULTS: Both colonic and duodenal EC cells expressed G protein-coupled receptors and facilitative transporters for sugars, free fatty acids, amino acids, and lipid amides. We find differential expression of nutrient receptor and transporters in EC cells obtained from duodenal and colonic EC cells. Duodenal EC cells have higher expression of tryptophan hydroxylase-1, sugar transporters GLUT2, GLUT5, and free fatty acid receptors 1 and 3 (FFAR1 and FFAR3). Colonic EC cells express higher levels of GLUT1, FFAR2, and FFAR4. CONCLUSIONS & INFERENCES: We highlight the diversity of EC cell physiology and identify differences in the regional sensing repertoire of EC cells to an assortment of nutrients. These data indicate that not all EC cells are similar and that differences in their physiological responses are likely dependent on their location within the GI tract.
BACKGROUND: Enterochromaffin (EC) cells within the gastrointestinal (GI) tract provide almost all body serotonin (5-hydroxytryptamine [5-HT]). Peripheral 5-HT, released from EC cells lining the gut wall, serves diverse physiological roles. These include modulating GI motility, bone formation, hepatic gluconeogenesis, thermogenesis, insulin resistance, and regulation of fat mass. Enterochromaffin cells are nutrient sensors, but which nutrients they are responsive to and how this changes in different parts of the GI tract are poorly understood. METHODS: To accurately undertake such an examination, we undertook the first isolation and purification of primary mouse EC cells from both the duodenum and colon in the same animal. This allowed us to compare, in an internally controlled manner, regional differences in the expression of nutrient sensors in EC cells using real-time PCR. KEY RESULTS: Both colonic and duodenal EC cells expressed G protein-coupled receptors and facilitative transporters for sugars, free fatty acids, amino acids, and lipid amides. We find differential expression of nutrient receptor and transporters in EC cells obtained from duodenal and colonic EC cells. Duodenal EC cells have higher expression of tryptophan hydroxylase-1, sugar transporters GLUT2, GLUT5, and free fatty acid receptors 1 and 3 (FFAR1 and FFAR3). Colonic EC cells express higher levels of GLUT1, FFAR2, and FFAR4. CONCLUSIONS & INFERENCES: We highlight the diversity of EC cell physiology and identify differences in the regional sensing repertoire of EC cells to an assortment of nutrients. These data indicate that not all EC cells are similar and that differences in their physiological responses are likely dependent on their location within the GI tract.
Authors: Lai Wei; Rajan Singh; Se Eun Ha; Alyce M Martin; Lauren A Jones; Byungchang Jin; Brian G Jorgensen; Hannah Zogg; Tyler Chervo; Andres Gottfried-Blackmore; Linda Nguyen; Aida Habtezion; Nick J Spencer; Damien J Keating; Kenton M Sanders; Seungil Ro Journal: Gastroenterology Date: 2021-03-02 Impact factor: 33.883
Authors: Mari L Lund; Kristoffer L Egerod; Maja S Engelstoft; Oksana Dmytriyeva; Elvar Theodorsson; Bhavik A Patel; Thue W Schwartz Journal: Mol Metab Date: 2018-03-10 Impact factor: 7.422
Authors: Alyce M Martin; Julian M Yabut; Jocelyn M Choo; Amanda J Page; Emily W Sun; Claire F Jessup; Steve L Wesselingh; Waliul I Khan; Geraint B Rogers; Gregory R Steinberg; Damien J Keating Journal: Proc Natl Acad Sci U S A Date: 2019-09-16 Impact factor: 11.205