The Diverse Metabolic Roles of Peripheral Serotonin.
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.
Discipline of Human Physiology and Centre for Neuroscience, Flinders University of South Australia, Adelaide 5042, Australia.
Alyce M
AM
Martin
Nutrition and Metabolism, South Australian Health and Medical Research Institute (SAHMRI), Adelaide 5001, Australia.|Adelaide Medical School, University of Adelaide, Adelaide 5005, Australia.
Richard L
RL
Young
Infection and Immunity, SAHMRI, Adelaide 5001, Australia.|SAHMRI Microbiome Research Laboratory, School of Medicine, Flinders University of South Australia, Adelaide 5042, Australia.
Lex
L
Leong
Infection and Immunity, SAHMRI, Adelaide 5001, Australia.|SAHMRI Microbiome Research Laboratory, School of Medicine, Flinders University of South Australia, Adelaide 5042, Australia.
Geraint B
GB
Rogers
Discipline of Human Physiology and Centre for Neuroscience, Flinders University of South Australia, Adelaide 5042, Australia.
Nick J
NJ
Spencer
Adelaide Medical School, University of Adelaide, Adelaide 5005, Australia.|Discipline of Anatomy and Histology, Flinders University of South Australia, Adelaide 5042, Australia.
Claire F
CF
Jessup
Discipline of Human Physiology and Centre for Neuroscience, Flinders University of South Australia, Adelaide 5042, Australia.|Nutrition and Metabolism, South Australian Health and Medical Research Institute (SAHMRI), Adelaide 5001, Australia.
Damien J
DJ
Keating
D000818:Animals; D004734:Energy Metabolism / Q000187:drug effects; D017615:Enteric Nervous System / Q000187:drug effects / Q000378:metabolism; D019858:Enteroendocrine Cells / Q000378:metabolism; D005769:Gastrointestinal Motility / Q000187:drug effects; D041981:Gastrointestinal Tract / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D012701:Serotonin / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects
D012701:Serotonin