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International Journal of Molecular... Jul 2022Depression is a common and serious disorder, characterized by symptoms like anhedonia, lack of energy, sad mood, low appetite, and sleep disturbances. This disease is... (Review)
Review
Depression is a common and serious disorder, characterized by symptoms like anhedonia, lack of energy, sad mood, low appetite, and sleep disturbances. This disease is very complex and not totally elucidated, in which diverse molecular and biological mechanisms are involved, such as neuroinflammation. There is a high need for the development of new therapies and gaining new insights into this disease is urgent. One important player in depression is the amino acid tryptophan. This amino acid can be metabolized in two important pathways in the context of depression: the serotonin and kynurenine pathways. These metabolic pathways of tryptophan are crucial in several processes that are linked with depression. Indeed, the maintenance of the balance of serotonin and kynurenine pathways is critical for the human physiological homeostasis. Thus, this narrative review aims to explore tryptophan metabolism (particularly in the serotonin and kynurenine pathways) in depression, starting with a global overview about these topics and ending with the focus on these pathways in neuroinflammation, stress, microbiota, and brain-derived neurotrophic factor regulation in this disease. Taken together, this information aims to clarify the metabolism of tryptophan in depression, particularly the serotonin and kynurenine pathways.
Topics: Depression; Humans; Kynurenine; Metabolic Networks and Pathways; Serotonin; Tryptophan
PubMed: 35955633
DOI: 10.3390/ijms23158493 -
Obesity Reviews : An Official Journal... Jul 2021The role of serotonin in food intake has been studied for decades. Food intake is mainly regulated by two brain circuitries: (i) the homeostatic circuitry, which matches... (Review)
Review
The role of serotonin in food intake has been studied for decades. Food intake is mainly regulated by two brain circuitries: (i) the homeostatic circuitry, which matches energy intake to energy expenditure, and (ii) the hedonic circuitry, which is involved in rewarding and motivational aspects of energy consumption. In the homeostatic circuitry, serotonergic signaling contributes to the integration of metabolic signals that convey the body's energy status and facilitates the ability to suppress food intake when homeostatic needs have been met. In the hedonic circuitry, serotonergic signaling may reduce reward-related, motivational food consumption. In contrast, peripherally acting serotonin promotes energy absorption and storage. Disturbed serotonergic signaling is associated with obesity, emphasizing the importance to understand the role of serotonergic signaling in food intake. However, unraveling the serotonin-mediated regulation of food intake is complex, as the effects of serotonergic signaling in different brain regions depend on the regional expression of serotonin receptor subtypes and downstream effects via connections to other brain regions. We therefore provide an overview of the effects of serotonergic signaling in brain regions of the homeostatic and hedonic regulatory systems on food intake. Furthermore, we discuss the disturbances in serotonergic signaling in obesity and its potential therapeutic implications.
Topics: Eating; Energy Metabolism; Humans; Obesity; Reward; Serotonin
PubMed: 33559362
DOI: 10.1111/obr.13210 -
Endocrine Reviews Aug 2019Serotonin is a phylogenetically ancient biogenic amine that has played an integral role in maintaining energy homeostasis for billions of years. In mammals, serotonin... (Review)
Review
Serotonin is a phylogenetically ancient biogenic amine that has played an integral role in maintaining energy homeostasis for billions of years. In mammals, serotonin produced within the central nervous system regulates behavior, suppresses appetite, and promotes energy expenditure by increasing sympathetic drive to brown adipose tissue. In addition to these central circuits, emerging evidence also suggests an important role for peripheral serotonin as a factor that enhances nutrient absorption and storage. Specifically, glucose and fatty acids stimulate the release of serotonin from the duodenum, promoting gut peristalsis and nutrient absorption. Serotonin also enters the bloodstream and interacts with multiple organs, priming the body for energy storage by promoting insulin secretion and de novo lipogenesis in the liver and white adipose tissue, while reducing lipolysis and the metabolic activity of brown and beige adipose tissue. Collectively, peripheral serotonin acts as an endocrine factor to promote the efficient storage of energy by upregulating lipid anabolism. Pharmacological inhibition of serotonin synthesis or signaling in key metabolic tissues are potential drug targets for obesity, type 2 diabetes, and nonalcoholic fatty liver disease (NAFLD).
Topics: Adipose Tissue, Brown; Adipose Tissue, White; Animals; Energy Metabolism; Humans; Lipid Metabolism; Serotonin; Signal Transduction
PubMed: 30901029
DOI: 10.1210/er.2018-00283 -
Canadian Medical Association Journal Apr 1970
Review
Topics: Animals; Brain; Chlorine; Humans; Hydroxyindoleacetic Acid; Phenylalanine; Rats; Reserpine; Serotonin; Serotonin Antagonists; Tryptophan
PubMed: 4910705
DOI: No ID Found -
Journal of Clinical Sleep Medicine :... Feb 2017Melatonin is an important neurohormone, which mediates circadian rhythms and the sleep cycle. As such, it is a popular and readily available supplement for the treatment...
STUDY OBJECTIVES
Melatonin is an important neurohormone, which mediates circadian rhythms and the sleep cycle. As such, it is a popular and readily available supplement for the treatment and prevention of sleep-related disorders including insomnia and jet lag. This study quantified melatonin in 30 commercial supplements, comprising different brands and forms and screened supplements for the presence of serotonin.
METHODS
A total of 31 supplements were analyzed by ultraperformance liquid chromatography with electrochemical detection for quantification of melatonin and serotonin. Presence of serotonin was confirmed through analysis by ultraperformance liquid chromatography with mass spectrometry detection.
RESULTS
Melatonin content was found to range from -83% to +478% of the labelled content. Additionally, lot-to-lot variable within a particular product varied by as much as 465%. This variability did not appear to be correlated with manufacturer or product type. Furthermore, serotonin (5-hydroxytryptamine), a related indoleamine and controlled substance used in the treatment of several neurological disorders, was identified in eight of the supplements at levels of 1 to 75 μg.
CONCLUSIONS
Melatonin content did not meet label within a 10% margin of the label claim in more than 71% of supplements and an additional 26% were found to contain serotonin. It is important that clinicians and patients have confidence in the quality of supplements used in the treatment of sleep disorders. To address this, manufacturers require increased controls to ensure melatonin supplements meet both their label claim, and also are free from contaminants, such as serotonin.
COMMENTARY
A commentary on this article appears in this issue on page 163.
Topics: Biological Products; Chromatography, Liquid; Dietary Supplements; Electrochemical Techniques; Mass Spectrometry; Melatonin; Serotonin
PubMed: 27855744
DOI: 10.5664/jcsm.6462 -
Gut Microbes 2022To gain insight into the complex microbiome-gut-brain axis in irritable bowel syndrome (IBS), several modalities of biological and clinical data must be combined. We...
To gain insight into the complex microbiome-gut-brain axis in irritable bowel syndrome (IBS), several modalities of biological and clinical data must be combined. We aimed to identify profiles of fecal microbiota and metabolites associated with IBS and to delineate specific phenotypes of IBS that represent potential pathophysiological mechanisms. Fecal metabolites were measured using proton nuclear magnetic resonance (H-NMR) spectroscopy and gut microbiome using shotgun metagenomic sequencing (MGS) in a combined dataset of 142 IBS patients and 120 healthy controls (HCs) with extensive clinical, biological and phenotype information. Data were analyzed using support vector classification and regression and kernel t-SNE. Microbiome and metabolome profiles could distinguish IBS and HC with an area-under-the-receiver-operator-curve of 77.3% and 79.5%, respectively, but this could be improved by combining microbiota and metabolites to 83.6%. No significant differences in predictive ability of the microbiome-metabolome data were observed between the three classical, stool pattern-based, IBS subtypes. However, unsupervised clustering showed distinct subsets of IBS patients based on fecal microbiome-metabolome data. These clusters could be related plasma levels of serotonin and its metabolite 5-hydroxyindoleacetate, effects of psychological stress on gastrointestinal (GI) symptoms, onset of IBS after stressful events, medical history of previous abdominal surgery, dietary caloric intake and IBS symptom duration. Furthermore, pathways in metabolic reaction networks were integrated with microbiota data, that reflect the host-microbiome interactions in IBS. The identified microbiome-metabolome signatures for IBS, associated with altered serotonin metabolism and unfavorable stress response related to GI symptoms, support the microbiota-gut-brain link in the pathogenesis of IBS.
Topics: Feces; Gastrointestinal Microbiome; Humans; Irritable Bowel Syndrome; Metabolome; Microbiota; Serotonin
PubMed: 35446234
DOI: 10.1080/19490976.2022.2063016 -
Advanced Science (Weinheim,... Feb 2023Emerging evidence reveals that amino acid metabolism plays an important role in ferroptotic cell death. The conversion of methionine to cysteine is well known to protect...
Emerging evidence reveals that amino acid metabolism plays an important role in ferroptotic cell death. The conversion of methionine to cysteine is well known to protect tumour cells from ferroptosis upon cysteine starvation through transamination. However, whether amino acids-produced metabolites participate in ferroptosis independent of the cysteine pathway is largely unknown. Here, the authors show that the tryptophan metabolites serotonin (5-HT) and 3-hydroxyanthranilic acid (3-HA) remarkably facilitate tumour cells to escape from ferroptosis distinct from cysteine-mediated ferroptosis inhibition. Mechanistically, both 5-HT and 3-HA act as potent radical trapping antioxidants (RTA) to eliminate lipid peroxidation, thereby inhibiting ferroptotic cell death. Monoamine oxidase A (MAOA) markedly abrogates the protective effect of 5-HT via degrading 5-HT. Deficiency of MAOA renders cancer cells resistant to ferroptosis upon 5-HT treatment. Kynureninase (KYNU), which is essential for 3-HA production, confers cells resistant to ferroptotic cell death, whereas 3-hydroxyanthranilate 3,4-dioxygenase (HAAO) significantly blocks 3-HA mediated ferroptosis inhibition by consuming 3-HA. In addition, the expression level of HAAO is positively correlated with lipid peroxidation and clinical outcome. Together, the findings demonstrate that tryptophan metabolism works as a new anti-ferroptotic pathway to promote tumour growth, and targeting this pathway will be a promising therapeutic approach for cancer treatment.
Topics: Humans; Tryptophan; Cysteine; Serotonin; Neoplasms; Lipid Peroxidation
PubMed: 36627132
DOI: 10.1002/advs.202204006 -
Journal of Neurophysiology Jun 2020The serotonergic system has been widely studied across animal taxa and different functional networks. This modulatory system is therefore well positioned to compare the... (Comparative Study)
Comparative Study Review
The serotonergic system has been widely studied across animal taxa and different functional networks. This modulatory system is therefore well positioned to compare the consequences of neuromodulation for sensory processing across species and modalities at multiple levels of sensory organization. Serotonergic neurons that innervate sensory networks often bidirectionally exchange information with these networks but also receive input representative of motor events or motivational state. This convergence of information supports serotonin's capacity for contextualizing sensory information according to the animal's physiological state and external events. At the level of sensory circuitry, serotonin can have variable effects due to differential projections across specific sensory subregions, as well as differential serotonin receptor type expression within those subregions. Functionally, this infrastructure may gate or filter sensory inputs to emphasize specific stimulus features or select among different streams of information. The near-ubiquitous presence of serotonin and other neuromodulators within sensory regions, coupled with their strong effects on stimulus representation, suggests that these signaling pathways should be considered integral components of sensory systems.
Topics: Animals; Auditory Perception; Nerve Net; Olfactory Perception; Receptors, Serotonin; Serotonergic Neurons; Serotonin; Signal Transduction
PubMed: 32401124
DOI: 10.1152/jn.00034.2020 -
Endocrinology and Metabolism (Seoul,... Dec 2021The liver is a vital organ that regulates systemic energy metabolism and many physiological functions. Nonalcoholic fatty liver disease (NAFLD) is the commonest cause of... (Review)
Review
The liver is a vital organ that regulates systemic energy metabolism and many physiological functions. Nonalcoholic fatty liver disease (NAFLD) is the commonest cause of chronic liver disease and end-stage liver failure. NAFLD is primarily caused by metabolic disruption of lipid and glucose homeostasis. Serotonin (5-hydroxytryptamine [5-HT]) is a biogenic amine with several functions in both the central and peripheral systems. 5-HT functions as a neurotransmitter in the brain and a hormone in peripheral tissues to regulate systemic energy homeostasis. Several recent studies have proposed various roles of 5-HT in hepatic metabolism and inflammation using tissue-specific knockout mice and 5-HT-receptor agonists/antagonists. This review compiles the most recent research on the relationship between 5-HT and hepatic metabolism, and the role of 5-HT signaling as a potential therapeutic target in NAFLD.
Topics: Animals; Energy Metabolism; Homeostasis; Mice; Non-alcoholic Fatty Liver Disease; Serotonin
PubMed: 34911172
DOI: 10.3803/EnM.2021.1331 -
Biology Open Jan 2022Serotonin is a neurotransmitter and a hormone that is typically associated with regulating our mood. However, the serotonin transporter and receptors are expressed...
Serotonin is a neurotransmitter and a hormone that is typically associated with regulating our mood. However, the serotonin transporter and receptors are expressed throughout the body, highlighting the much broader, systemic role of serotonin in regulating human physiology. A substantial body of data strongly implicates serotonin as a fundamental regulator of endocytosis and endocytic sorting. Serotonin has the potential to enhance endocytosis through three distinct mechanisms - serotonin signalling, serotonylation and insertion into the plasma membrane - although the interplay and relationship between these mechanisms has not yet been explored. Endocytosis is central to the cellular response to the extracellular environment, controlling receptor distribution on the plasma membrane to modulate signalling, neurotransmitter release and uptake, circulating protein and lipid cargo uptake, and amino acid internalisation for cell proliferation. Uncovering the range of cellular and physiological circumstances in which serotonin regulates endocytosis is of great interest for our understanding of how serotonin regulates mood, and also the fundamental understanding of endocytosis and its regulation throughout the body. This article has an associated Future Leader to Watch interview with the first author of the paper.
Topics: Cell Membrane; Endocytosis; Endosomes; Humans; Protein Transport; Serotonin
PubMed: 35076063
DOI: 10.1242/bio.059057