A Systems Biology Approach to Investigating the Interaction between Serotonin Synthesis by Tryptophan Hydroxylase and the Metabolic Homeostasis
Obesity has become a global public health and economic problem. Obesity is a major risk factor for a number of complications, such as type 2 diabetes, cardiovascular disease, fatty liver disease, and cancer. Serotonin (5-hydroxytryptamine [5-HT]) is a biogenic monoamine that plays various roles in m...
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| Veröffentlicht in: | International journal of molecular sciences 2021-02, Vol.22 (5), p.2452 |
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| creator | Park, Suhyeon Kim, Yumin Lee, Jibeom Lee, Jeong Yun Kim, Hail Lee, Sunjae Oh, Chang-Myung |
| description | Obesity has become a global public health and economic problem. Obesity is a major risk factor for a number of complications, such as type 2 diabetes, cardiovascular disease, fatty liver disease, and cancer. Serotonin (5-hydroxytryptamine [5-HT]) is a biogenic monoamine that plays various roles in metabolic homeostasis. It is well known that central 5-HT regulates appetite and mood. Several 5-HT receptor agonists and selective serotonin receptor uptake inhibitors (SSRIs) have shown beneficial effects on appetite and mood control in clinics. Although several genetic polymorphisms related to 5-HT synthesis and its receptors are strongly associated with obesity, there is little evidence of the role of peripheral 5-HT in human metabolism. In this study, we performed a systemic analysis of transcriptome data from the Genotype-Tissue Expression (GTEX) database. We investigated the expression of 5-HT and tryptophan hydroxylase (TPH), the rate-limiting enzyme of 5-HT biosynthesis, in the human brain and peripheral tissues. We also performed differential gene expression analysis and predicted changes in metabolites by comparing gene expressions of tissues with high TPH expression to the gene expressions of tissues with low TPH expression. Our analyses provide strong evidence that serotonin plays an important role in the regulation of metabolic homeostasis in humans. |
| doi_str_mv | 10.3390/ijms22052452 |
| format | Article |
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Obesity is a major risk factor for a number of complications, such as type 2 diabetes, cardiovascular disease, fatty liver disease, and cancer. Serotonin (5-hydroxytryptamine [5-HT]) is a biogenic monoamine that plays various roles in metabolic homeostasis. It is well known that central 5-HT regulates appetite and mood. Several 5-HT receptor agonists and selective serotonin receptor uptake inhibitors (SSRIs) have shown beneficial effects on appetite and mood control in clinics. Although several genetic polymorphisms related to 5-HT synthesis and its receptors are strongly associated with obesity, there is little evidence of the role of peripheral 5-HT in human metabolism. In this study, we performed a systemic analysis of transcriptome data from the Genotype-Tissue Expression (GTEX) database. We investigated the expression of 5-HT and tryptophan hydroxylase (TPH), the rate-limiting enzyme of 5-HT biosynthesis, in the human brain and peripheral tissues. We also performed differential gene expression analysis and predicted changes in metabolites by comparing gene expressions of tissues with high TPH expression to the gene expressions of tissues with low TPH expression. Our analyses provide strong evidence that serotonin plays an important role in the regulation of metabolic homeostasis in humans.</description><identifier>ISSN: 1422-0067</identifier><identifier>ISSN: 1661-6596</identifier><identifier>EISSN: 1422-0067</identifier><identifier>DOI: 10.3390/ijms22052452</identifier><identifier>PMID: 33671067</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Adipocytes ; Adipose Tissue - metabolism ; Biosynthesis ; Brain - metabolism ; Cardiovascular diseases ; Cell growth ; Colorectal cancer ; Datasets ; Diabetes ; Diabetes mellitus (non-insulin dependent) ; Energy ; Enzymes ; Fatty acids ; Fatty liver ; Gene expression ; Gene polymorphism ; Genes ; Homeostasis ; Humans ; Inflammation ; Intestines - physiology ; Lipids ; Liver cancer ; Liver diseases ; Metabolic disorders ; Metabolites ; Metabolome ; Mood ; Obesity ; Pituitary gland ; Public health ; Risk analysis ; Risk factors ; Roles ; Serotonin ; Serotonin - metabolism ; Small intestine ; Systems Biology ; Transcriptome ; Transcriptomes ; Tryptophan ; Tryptophan hydroxylase ; Tryptophan Hydroxylase - genetics ; Tryptophan Hydroxylase - metabolism</subject><ispartof>International journal of molecular sciences, 2021-02, Vol.22 (5), p.2452</ispartof><rights>2021. This work is licensed under http://creativecommons.org/licenses/by/3.0/ (the “License”). 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Obesity is a major risk factor for a number of complications, such as type 2 diabetes, cardiovascular disease, fatty liver disease, and cancer. Serotonin (5-hydroxytryptamine [5-HT]) is a biogenic monoamine that plays various roles in metabolic homeostasis. It is well known that central 5-HT regulates appetite and mood. Several 5-HT receptor agonists and selective serotonin receptor uptake inhibitors (SSRIs) have shown beneficial effects on appetite and mood control in clinics. Although several genetic polymorphisms related to 5-HT synthesis and its receptors are strongly associated with obesity, there is little evidence of the role of peripheral 5-HT in human metabolism. In this study, we performed a systemic analysis of transcriptome data from the Genotype-Tissue Expression (GTEX) database. We investigated the expression of 5-HT and tryptophan hydroxylase (TPH), the rate-limiting enzyme of 5-HT biosynthesis, in the human brain and peripheral tissues. We also performed differential gene expression analysis and predicted changes in metabolites by comparing gene expressions of tissues with high TPH expression to the gene expressions of tissues with low TPH expression. Our analyses provide strong evidence that serotonin plays an important role in the regulation of metabolic homeostasis in humans.</description><subject>Adipocytes</subject><subject>Adipose Tissue - metabolism</subject><subject>Biosynthesis</subject><subject>Brain - metabolism</subject><subject>Cardiovascular diseases</subject><subject>Cell growth</subject><subject>Colorectal cancer</subject><subject>Datasets</subject><subject>Diabetes</subject><subject>Diabetes mellitus (non-insulin dependent)</subject><subject>Energy</subject><subject>Enzymes</subject><subject>Fatty acids</subject><subject>Fatty liver</subject><subject>Gene expression</subject><subject>Gene polymorphism</subject><subject>Genes</subject><subject>Homeostasis</subject><subject>Humans</subject><subject>Inflammation</subject><subject>Intestines - physiology</subject><subject>Lipids</subject><subject>Liver cancer</subject><subject>Liver diseases</subject><subject>Metabolic disorders</subject><subject>Metabolites</subject><subject>Metabolome</subject><subject>Mood</subject><subject>Obesity</subject><subject>Pituitary gland</subject><subject>Public health</subject><subject>Risk analysis</subject><subject>Risk factors</subject><subject>Roles</subject><subject>Serotonin</subject><subject>Serotonin - metabolism</subject><subject>Small intestine</subject><subject>Systems Biology</subject><subject>Transcriptome</subject><subject>Transcriptomes</subject><subject>Tryptophan</subject><subject>Tryptophan hydroxylase</subject><subject>Tryptophan Hydroxylase - genetics</subject><subject>Tryptophan Hydroxylase - metabolism</subject><issn>1422-0067</issn><issn>1661-6596</issn><issn>1422-0067</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNpdkU1vFDEMhiNERUvhxhlF4sKhW_IxX7kgbavCViri0HKOPBnPblYzyZBkS-dX9C-T0lItnGzZj1_Zfgl5x9mplIp9stsxCsFKUZTiBTnihRALxqr65V5-SF7HuGVMSFGqV-RQyqrmuX5E7pf0eo4Jx0jPrB_8eqbLaQoezIYmTy_dLcZk15CsW9O0wVxJGMAk6x1tMf1CdPQag0_e2ZzNLkPRRtrO9CbMU_LTBhxdzV3wd_MAESm47o_SN0zQ-sEauvIj-pggz70hBz0MEd8-xWPy48vFzflqcfX96-X58mphCi7SAgQwhbLteQ-y6yRD2QNreAcNq8pGiRKRt1yxqgfed8agYAxZ0zAJtVRcHpPPj7rTrh2xM-hSgEFPwY4QZu3B6n87zm702t_qWpV13Ygs8PFJIPifu_wkPdpocBjAod9FLQrVFEpJVWX0w3_o1u-Cy-c9ULWspCxlpk4eKRN8jAH752U40w9O632nM_5-_4Bn-K-18jfvPqit</recordid><startdate>20210228</startdate><enddate>20210228</enddate><creator>Park, Suhyeon</creator><creator>Kim, Yumin</creator><creator>Lee, Jibeom</creator><creator>Lee, Jeong Yun</creator><creator>Kim, Hail</creator><creator>Lee, Sunjae</creator><creator>Oh, Chang-Myung</creator><general>MDPI AG</general><general>MDPI</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>MBDVC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-2083-6660</orcidid><orcidid>https://orcid.org/0000-0002-6428-5936</orcidid></search><sort><creationdate>20210228</creationdate><title>A Systems Biology Approach to Investigating the Interaction between Serotonin Synthesis by Tryptophan Hydroxylase and the Metabolic Homeostasis</title><author>Park, Suhyeon ; Kim, Yumin ; Lee, Jibeom ; Lee, Jeong Yun ; Kim, Hail ; Lee, Sunjae ; Oh, Chang-Myung</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c412t-a2a09e3bf1fa3dd30e3fa081da80658925ee1b1906fa1fdcce200e08803a73913</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Adipocytes</topic><topic>Adipose Tissue - metabolism</topic><topic>Biosynthesis</topic><topic>Brain - metabolism</topic><topic>Cardiovascular diseases</topic><topic>Cell growth</topic><topic>Colorectal cancer</topic><topic>Datasets</topic><topic>Diabetes</topic><topic>Diabetes mellitus (non-insulin dependent)</topic><topic>Energy</topic><topic>Enzymes</topic><topic>Fatty acids</topic><topic>Fatty liver</topic><topic>Gene expression</topic><topic>Gene polymorphism</topic><topic>Genes</topic><topic>Homeostasis</topic><topic>Humans</topic><topic>Inflammation</topic><topic>Intestines - physiology</topic><topic>Lipids</topic><topic>Liver cancer</topic><topic>Liver diseases</topic><topic>Metabolic disorders</topic><topic>Metabolites</topic><topic>Metabolome</topic><topic>Mood</topic><topic>Obesity</topic><topic>Pituitary gland</topic><topic>Public health</topic><topic>Risk analysis</topic><topic>Risk factors</topic><topic>Roles</topic><topic>Serotonin</topic><topic>Serotonin - metabolism</topic><topic>Small intestine</topic><topic>Systems Biology</topic><topic>Transcriptome</topic><topic>Transcriptomes</topic><topic>Tryptophan</topic><topic>Tryptophan hydroxylase</topic><topic>Tryptophan Hydroxylase - genetics</topic><topic>Tryptophan Hydroxylase - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Park, Suhyeon</creatorcontrib><creatorcontrib>Kim, Yumin</creatorcontrib><creatorcontrib>Lee, Jibeom</creatorcontrib><creatorcontrib>Lee, Jeong Yun</creatorcontrib><creatorcontrib>Kim, Hail</creatorcontrib><creatorcontrib>Lee, Sunjae</creatorcontrib><creatorcontrib>Oh, Chang-Myung</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Proquest Health & Medical Complete</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>AUTh Library subscriptions: ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</collection><collection>ProQuest Research Library</collection><collection>Research Library (Corporate)</collection><collection>Publicly Available Content (ProQuest)</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>International journal of molecular sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Park, Suhyeon</au><au>Kim, Yumin</au><au>Lee, Jibeom</au><au>Lee, Jeong Yun</au><au>Kim, Hail</au><au>Lee, Sunjae</au><au>Oh, Chang-Myung</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A Systems Biology Approach to Investigating the Interaction between Serotonin Synthesis by Tryptophan Hydroxylase and the Metabolic Homeostasis</atitle><jtitle>International journal of molecular sciences</jtitle><addtitle>Int J Mol Sci</addtitle><date>2021-02-28</date><risdate>2021</risdate><volume>22</volume><issue>5</issue><spage>2452</spage><pages>2452-</pages><issn>1422-0067</issn><issn>1661-6596</issn><eissn>1422-0067</eissn><abstract>Obesity has become a global public health and economic problem. Obesity is a major risk factor for a number of complications, such as type 2 diabetes, cardiovascular disease, fatty liver disease, and cancer. Serotonin (5-hydroxytryptamine [5-HT]) is a biogenic monoamine that plays various roles in metabolic homeostasis. It is well known that central 5-HT regulates appetite and mood. Several 5-HT receptor agonists and selective serotonin receptor uptake inhibitors (SSRIs) have shown beneficial effects on appetite and mood control in clinics. Although several genetic polymorphisms related to 5-HT synthesis and its receptors are strongly associated with obesity, there is little evidence of the role of peripheral 5-HT in human metabolism. In this study, we performed a systemic analysis of transcriptome data from the Genotype-Tissue Expression (GTEX) database. We investigated the expression of 5-HT and tryptophan hydroxylase (TPH), the rate-limiting enzyme of 5-HT biosynthesis, in the human brain and peripheral tissues. We also performed differential gene expression analysis and predicted changes in metabolites by comparing gene expressions of tissues with high TPH expression to the gene expressions of tissues with low TPH expression. Our analyses provide strong evidence that serotonin plays an important role in the regulation of metabolic homeostasis in humans.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>33671067</pmid><doi>10.3390/ijms22052452</doi><orcidid>https://orcid.org/0000-0002-2083-6660</orcidid><orcidid>https://orcid.org/0000-0002-6428-5936</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Adipocytes Adipose Tissue - metabolism Biosynthesis Brain - metabolism Cardiovascular diseases Cell growth Colorectal cancer Datasets Diabetes Diabetes mellitus (non-insulin dependent) Energy Enzymes Fatty acids Fatty liver Gene expression Gene polymorphism Genes Homeostasis Humans Inflammation Intestines - physiology Lipids Liver cancer Liver diseases Metabolic disorders Metabolites Metabolome Mood Obesity Pituitary gland Public health Risk analysis Risk factors Roles Serotonin Serotonin - metabolism Small intestine Systems Biology Transcriptome Transcriptomes Tryptophan Tryptophan hydroxylase Tryptophan Hydroxylase - genetics Tryptophan Hydroxylase - metabolism |
| title | A Systems Biology Approach to Investigating the Interaction between Serotonin Synthesis by Tryptophan Hydroxylase and the Metabolic Homeostasis |
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