Diet differentially regulates enterochromaffin cell serotonin content, density and nutrient sensitivity in the mouse small and large intestine

Research output: Contribution to journalArticle

Abstract

Background: Enterochromaffin (EC) cells are specialized enteroendocrine cells lining the gastrointestinal (GI) tract and the source of almost all serotonin (5-hydroxytryptamine; 5-HT) in the body. Gut-derived 5-HT has a plethora of physiological roles, including regulation of gastrointestinal motility, and has been implicated as a driver of obesity and metabolic disease. This is due to 5-HT influencing key metabolic processes, such as hepatic gluconeogenesis, adipose tissue lipolysis and hindering thermogenic capacity. Increased circulating 5-HT occurs in humans with obesity and type 2 diabetes. However, despite the known metabolic roles of gut-derived 5-HT, the mechanisms underlying the cellular-level change in EC cells under obesogenic conditions remains unknown. Methods: We use a mouse model of diet-induced obesity (DIO) to identify the regional changes that occur in primary EC cells from the duodenum and colon. Transcriptional changes in the nutrient sensing profile of primary EC cells were assessed, and responses to nutrient stimuli in culture were determined by 5-HT ELISA. Key Results: We find that obesogenic conditions affect EC cells in a region-dependent manner. Duodenal EC cells from DIO mice have impaired sugar sensing even in the presence of increased 5-HT content per cell, while colonic EC cell numbers are significantly increased, but have unaltered nutrient sensing capacity. Conclusions & Inferences: Our findings from this study add novel insights into the mechanisms by which functional changes to EC cells occur at a cellular level, which may contribute to the altered circulating 5-HT seen with obesity and metabolic disease, and associated gastrointestinal disorders.

Original languageEnglish
Article numbere13869
Number of pages9
JournalNeurogastroenterology and Motility
Volume32
Issue number8
Early online date7 May 2020
DOIs
Publication statusPublished - 1 Aug 2020

Keywords

  • enterochromaffin
  • gastrointestinal
  • nutrients
  • obesity
  • serotonin

Fingerprint Dive into the research topics of 'Diet differentially regulates enterochromaffin cell serotonin content, density and nutrient sensitivity in the mouse small and large intestine'. Together they form a unique fingerprint.

  • Cite this