The Diverse Metabolic Roles of Peripheral Serotonin

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.

Zebrafish fin regeneration involves transient serotonin synthesis

“…11 The monoamine is distributed by blood platelets throughout the entire body, where it modulates diverse non-neural processes, including various metabolic roles, vascular constriction, platelet aggregation, inflammation, insulin release, intestinal motility, and bladder control. [12][13][14] Behavioral studies in zebrafish have demonstrated the conservation among vertebrates of the different neurological functions of serotonin, as well as of the effects of drugs, which affect the serotonergic system. 15 In zebrafish peripheral organs, serotonin was detected in Merkel-like cells of the taste buds, in neuroepithelial cells of the skin, and joint-associated fibroblasts in the fin.…”

Identification of salivary and plasma biomarkers for obesity in children by non-targeted metabolomic analysis

“…Serotonin reduction in plasma was highly significant in obese children. Depression and antidepressant drugs are both associated with increased risk of obesity presumably due to a reduction in serotonin or the serotonin transporter [24,25].…”

“…Reduced serotonin has been found in cord blood where this reduction was associated with rapid postnatal weight gain [26]. The understanding of serotonin function has been broadly expanded to include obesity and diabetes [25]. (Tables 4 and 5).…”

Quantum Analysis of the Interaction of Salbutamol and Nt

“…[11] Exogenous 5-HT significantly attenuates the thermogenic potential of the β-adrenergic agonist receptor. [12] Bronchodilator drugs are widely used therapeutic agents for the treatment of asthma and COPD. [13,14] The standard treatment of acute severe asthma is the use of short-acting inhaled agonists (SB), systemic corticosteroids and supplemental oxygen.…”