The diverse metabolic roles of peripheral serotonin

Alyce M. Martin, Richard L. Young, Lex Leong, Geraint B Rogers, Nick J Spencer, Claire F Jessup, Damien J Keating

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Serotonin (5-hydroxytryptamine, 5-HT) is a multi-functional bioamine with important signaling roles in a range of physiological pathways. Almost all the 5-HT in our body is synthesized in specialized enteroendocrine cells within the gastrointestinal (GI) mucosa called enterochromaffin (EC) cells. These cells provide all our circulating 5-HT. While we have long appreciated the important roles of 5-HT within the gut including the modulation of GI motility, there is recently emerging evidence of the physiological and clinical significance of gut-derived 5-HT outside of the gut. These include roles in regulating glucose homeostasis, lipid metabolism, bone density and diseases associated with metabolic syndrome, such as obesity and type 2 diabetes. While a new picture has developed in the last decade regarding the various metabolic roles of peripheral serotonin, so too has our understanding of the physiology of EC cells. Given they are scattered throughout the lining of the GI tract amongst the epithelial cell layer, these cells are typically difficult to study. Advances in isolation procedures now allow the study of pure EC cell cultures and single cells, enabling studies of EC cell physiology to occur. These are sensory cells, capable of integrating cues from ingested nutrient, the enteric nervous system and the gut microbiome. Thus, levels of peripheral 5-HT can be modulated by a multitude of factors, and this will have both local and systemic effects to regulate a raft of physiological pathways related to metabolism and obesity.

Original languageEnglish
Publication statusE-pub ahead of print - 1 Mar 2017


  • Journal Article

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