Cited by 262Regulation of Appetite and ObesityGastrointestinal motility and disordersAdipokines, Inflammation, and Metabolic Diseases

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The Diverse Metabolic Roles of Peripheral Serotonin

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Martin, Alyce M., Young, Richard L., Leong, Lex, Rogers, Geraint B., Spencer, Nick J., Jessup, Claire F., Keating, Damien J.·2017·Endocrinology

DOI 10.1210/en.2016-1839

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Abstract

Serotonin (5-hydroxytryptamine or 5-HT) is a multifunctional bioamine with important signaling roles in a range of physiological pathways. Almost all of the 5-HT in our bodies is synthesized in specialized enteroendocrine cells within the gastrointestinal (GI) mucosa called enterochromaffin (EC) cells. These cells provide all of our circulating 5-HT. We have long appreciated the important contributions of 5-HT within the gut, including its role in modulating GI motility. However, evidence of the physiological and clinical significance of gut-derived 5-HT outside of the gut has recently emerged, implicating 5-HT in regulation of glucose homeostasis, lipid metabolism, bone density, and diseases associated with metabolic syndrome, such as obesity and type 2 diabetes. Although 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 that they are scattered throughout the lining of the GI tract within 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. EC cells are sensory cells that are capable of integrating cues from ingested nutrients, the enteric nervous system, and the gut microbiome. Thus, levels of peripheral 5-HT can be modulated by a multitude of factors, resulting in both local and systemic effects for the regulation of a raft of physiological pathways related to metabolism and obesity.

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Authors: Martin, A. M., Young, R. L., Leong, L., Rogers, G. B., Spencer, N. J., Jessup, C. F., & Keating, D. J.
Affiliations: Flinders University (AU)
South Australian Health and Medical Research Institute (AU)
ORCID: Martin, Alyce M.
Young, Richard L.
Leong, Lex
Rogers, Geraint B.
Spencer, Nick J.
Jessup, Claire F.
Keating, Damien J.
Venue: Endocrinology
Publisher: The Endocrine Society
Published: 2017-03-01
Volume: 158
Issue: 5
Pages: 1049-1063
ISSN: 0013-7227 (ISSN-L)
1945-7170
DOI: 10.1210/en.2016-1839
OpenAlex: W2611159081
Cited by: 261
References: 166
Citations by year: 2026: 29 · 2025: 18 · 2024: 41 · 2023: 19 · 2022: 38 · 2021: 43 · 2020: 26 · 2019: 26 · 2018: 17 · 2017: 3
FWCI: 2.38
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Endocrinology (publishedVersion)
PubMed (publishedVersion)
Funders: Flinders University
University of South Australia
Topics: Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
Keywords: peripheral serotonin, enterochromaffin cells, enteroendocrine cells, gut-brain axis, glucose homeostasis, lipid metabolism, bone mineral density, metabolic syndrome, obesity, type 2 diabetes, gut microbiota, enteric nervous system, gastrointestinal motility
MeSH terms: Animals, Energy Metabolism, Gastrointestinal Motility, Humans, Serotonin, Signal Transduction, Enteric Nervous System, Enteroendocrine Cells, Gastrointestinal Tract

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The Diverse Metabolic Roles of Peripheral Serotonin

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