Melanin-concentrating hormone receptor mutations and human obesity: functional analysis
Melanin‐concentrating hormone (MCH), a neuropeptide highly expressed in the lateral hypothalamus, has an important role in the regulation of energy balance and body weight in rodents. We examined whether mutations in the two known MCH receptors might be associated with obesity‐related phenotypes in...
Gespeichert in:
| Veröffentlicht in: | Obesity (Silver Spring, Md.) Md.), 2004-05, Vol.12 (5), p.743-749 |
|---|---|
| Hauptverfasser: | , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 749 |
|---|---|
| container_issue | 5 |
| container_start_page | 743 |
| container_title | Obesity (Silver Spring, Md.) |
| container_volume | 12 |
| creator | Gibson, W.T Pissios, P Trombly, D.J Luan, J Keogh, J Wareham, N.J Maratos-Flier, E O'Rahilly, S Farooqi, I.S |
| description | Melanin‐concentrating hormone (MCH), a neuropeptide highly expressed in the lateral hypothalamus, has an important role in the regulation of energy balance and body weight in rodents. We examined whether mutations in the two known MCH receptors might be associated with obesity‐related phenotypes in humans. Among 106 subjects with severe early onset obesity and a history of hyperphagia, we found two missense variants in MCHR1: Y181H and R248Q. Neither of these was found in 192 normal weight controls. R248Q cosegregated with obesity across two generations; family data were unavailable for Y181H. When expressed in HEK293 cells, R248Q showed no evidence of constitutive activation or ligand hypersensitivity for extracellular signal‐regulated kinase phosphorylation. In addition, R248Q showed no enhanced suppression of cAMP generation. Two common single‐nucleotide polymorphisms were found to be in linkage disequilibrium: g.‐114A>G and c.39C>T. No association between either of these single‐nucleotide polymorphisms and obesity‐related phenotypes was found among a population cohort of 541 whites. Only two rare noncoding variants were found in MCHR2. In conclusion, mutations in the MCH receptors are not commonly found in humans with severe early onset obesity. Clarification of the relationship of these variants to obesity must await study in other populations and/or in genetically modified mice. |
| doi_str_mv | 10.1038/oby.2004.89 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_71967263</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2726966581</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4681-3f922c3b280944fe2a620d61b3ce5afc055b2687c8e9f7498dd314c9319609ba3</originalsourceid><addsrcrecordid>eNp90EFrFTEQB_Agiq3Vk3ddELzIPmeS3WziTYu2QqUHLeIpZLOz7Zbd5DXZRfbbm-d7tODBUwLzm8nkz9hLhA2CUO9Du244QLVR-hE7xrqGUtVcPc53aLBsBBdH7FlKtwAoK4VP2RHWKCXX4pj9_Eaj9YMvXfCO_BztPPjr4ibEKXgqIjnaziEW0zLnSvCpsL4rbpbJ-iK0lIZ5_VD0i3e7oh1z1Y5rGtJz9qS3Y6IXh_OEXX35_OP0vLy4PPt6-vGidJVUWIpec-5EyxXoquqJW8mhk9gKR7XtHdR1y6VqnCLdN5VWXSewclqglqBbK07Y2_3cbQx3C6XZTENyNOZPUViSaTJsuBQZvvkH3oYl5m2TySlCo1TVqKze7ZWLIaVIvdnGYbJxzWjnlMlpm13aRumsXx1mLu1E3YM9xJsB7MHvYaT1f7PM5adfCBJzy-t9i7fzEum-J9sd_fvqQfQ2GHsdh2SuvnNAAQhcIRfiDz4Snfk</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1030788478</pqid></control><display><type>article</type><title>Melanin-concentrating hormone receptor mutations and human obesity: functional analysis</title><source>MEDLINE</source><source>Wiley Online Library Journals Frontfile Complete</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Wiley Free Content</source><creator>Gibson, W.T ; Pissios, P ; Trombly, D.J ; Luan, J ; Keogh, J ; Wareham, N.J ; Maratos-Flier, E ; O'Rahilly, S ; Farooqi, I.S</creator><creatorcontrib>Gibson, W.T ; Pissios, P ; Trombly, D.J ; Luan, J ; Keogh, J ; Wareham, N.J ; Maratos-Flier, E ; O'Rahilly, S ; Farooqi, I.S</creatorcontrib><description>Melanin‐concentrating hormone (MCH), a neuropeptide highly expressed in the lateral hypothalamus, has an important role in the regulation of energy balance and body weight in rodents. We examined whether mutations in the two known MCH receptors might be associated with obesity‐related phenotypes in humans. Among 106 subjects with severe early onset obesity and a history of hyperphagia, we found two missense variants in MCHR1: Y181H and R248Q. Neither of these was found in 192 normal weight controls. R248Q cosegregated with obesity across two generations; family data were unavailable for Y181H. When expressed in HEK293 cells, R248Q showed no evidence of constitutive activation or ligand hypersensitivity for extracellular signal‐regulated kinase phosphorylation. In addition, R248Q showed no enhanced suppression of cAMP generation. Two common single‐nucleotide polymorphisms were found to be in linkage disequilibrium: g.‐114A>G and c.39C>T. No association between either of these single‐nucleotide polymorphisms and obesity‐related phenotypes was found among a population cohort of 541 whites. Only two rare noncoding variants were found in MCHR2. In conclusion, mutations in the MCH receptors are not commonly found in humans with severe early onset obesity. Clarification of the relationship of these variants to obesity must await study in other populations and/or in genetically modified mice.</description><identifier>ISSN: 1071-7323</identifier><identifier>ISSN: 1930-7381</identifier><identifier>EISSN: 1550-8528</identifier><identifier>EISSN: 1930-739X</identifier><identifier>DOI: 10.1038/oby.2004.89</identifier><identifier>PMID: 15166293</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>Amino Acid Sequence ; association study ; Base Sequence ; ERK phosphorylation ; GTP-Binding Proteins - physiology ; G‐protein‐coupled receptors ; Humans ; Hyperphagia - genetics ; Linkage Disequilibrium ; MCHR1 ; MCHR2 ; Mitogen-Activated Protein Kinases - metabolism ; Molecular Sequence Data ; Mutation ; Obesity - genetics ; Phosphorylation ; Polymorphism, Single Nucleotide ; Receptors, G-Protein-Coupled ; Receptors, Pituitary Hormone - chemistry ; Receptors, Pituitary Hormone - genetics</subject><ispartof>Obesity (Silver Spring, Md.), 2004-05, Vol.12 (5), p.743-749</ispartof><rights>2004 North American Association for the Study of Obesity (NAASO)</rights><rights>Copyright 2004 NAASO</rights><rights>Copyright Nature Publishing Group May 2004</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4681-3f922c3b280944fe2a620d61b3ce5afc055b2687c8e9f7498dd314c9319609ba3</citedby><cites>FETCH-LOGICAL-c4681-3f922c3b280944fe2a620d61b3ce5afc055b2687c8e9f7498dd314c9319609ba3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1038%2Foby.2004.89$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1038%2Foby.2004.89$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,778,782,1414,1430,27907,27908,45557,45558,46392,46816</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15166293$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Gibson, W.T</creatorcontrib><creatorcontrib>Pissios, P</creatorcontrib><creatorcontrib>Trombly, D.J</creatorcontrib><creatorcontrib>Luan, J</creatorcontrib><creatorcontrib>Keogh, J</creatorcontrib><creatorcontrib>Wareham, N.J</creatorcontrib><creatorcontrib>Maratos-Flier, E</creatorcontrib><creatorcontrib>O'Rahilly, S</creatorcontrib><creatorcontrib>Farooqi, I.S</creatorcontrib><title>Melanin-concentrating hormone receptor mutations and human obesity: functional analysis</title><title>Obesity (Silver Spring, Md.)</title><addtitle>Obes Res</addtitle><description>Melanin‐concentrating hormone (MCH), a neuropeptide highly expressed in the lateral hypothalamus, has an important role in the regulation of energy balance and body weight in rodents. We examined whether mutations in the two known MCH receptors might be associated with obesity‐related phenotypes in humans. Among 106 subjects with severe early onset obesity and a history of hyperphagia, we found two missense variants in MCHR1: Y181H and R248Q. Neither of these was found in 192 normal weight controls. R248Q cosegregated with obesity across two generations; family data were unavailable for Y181H. When expressed in HEK293 cells, R248Q showed no evidence of constitutive activation or ligand hypersensitivity for extracellular signal‐regulated kinase phosphorylation. In addition, R248Q showed no enhanced suppression of cAMP generation. Two common single‐nucleotide polymorphisms were found to be in linkage disequilibrium: g.‐114A>G and c.39C>T. No association between either of these single‐nucleotide polymorphisms and obesity‐related phenotypes was found among a population cohort of 541 whites. Only two rare noncoding variants were found in MCHR2. In conclusion, mutations in the MCH receptors are not commonly found in humans with severe early onset obesity. Clarification of the relationship of these variants to obesity must await study in other populations and/or in genetically modified mice.</description><subject>Amino Acid Sequence</subject><subject>association study</subject><subject>Base Sequence</subject><subject>ERK phosphorylation</subject><subject>GTP-Binding Proteins - physiology</subject><subject>G‐protein‐coupled receptors</subject><subject>Humans</subject><subject>Hyperphagia - genetics</subject><subject>Linkage Disequilibrium</subject><subject>MCHR1</subject><subject>MCHR2</subject><subject>Mitogen-Activated Protein Kinases - metabolism</subject><subject>Molecular Sequence Data</subject><subject>Mutation</subject><subject>Obesity - genetics</subject><subject>Phosphorylation</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Receptors, G-Protein-Coupled</subject><subject>Receptors, Pituitary Hormone - chemistry</subject><subject>Receptors, Pituitary Hormone - genetics</subject><issn>1071-7323</issn><issn>1930-7381</issn><issn>1550-8528</issn><issn>1930-739X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp90EFrFTEQB_Agiq3Vk3ddELzIPmeS3WziTYu2QqUHLeIpZLOz7Zbd5DXZRfbbm-d7tODBUwLzm8nkz9hLhA2CUO9Du244QLVR-hE7xrqGUtVcPc53aLBsBBdH7FlKtwAoK4VP2RHWKCXX4pj9_Eaj9YMvXfCO_BztPPjr4ibEKXgqIjnaziEW0zLnSvCpsL4rbpbJ-iK0lIZ5_VD0i3e7oh1z1Y5rGtJz9qS3Y6IXh_OEXX35_OP0vLy4PPt6-vGidJVUWIpec-5EyxXoquqJW8mhk9gKR7XtHdR1y6VqnCLdN5VWXSewclqglqBbK07Y2_3cbQx3C6XZTENyNOZPUViSaTJsuBQZvvkH3oYl5m2TySlCo1TVqKze7ZWLIaVIvdnGYbJxzWjnlMlpm13aRumsXx1mLu1E3YM9xJsB7MHvYaT1f7PM5adfCBJzy-t9i7fzEum-J9sd_fvqQfQ2GHsdh2SuvnNAAQhcIRfiDz4Snfk</recordid><startdate>200405</startdate><enddate>200405</enddate><creator>Gibson, W.T</creator><creator>Pissios, P</creator><creator>Trombly, D.J</creator><creator>Luan, J</creator><creator>Keogh, J</creator><creator>Wareham, N.J</creator><creator>Maratos-Flier, E</creator><creator>O'Rahilly, S</creator><creator>Farooqi, I.S</creator><general>Blackwell Publishing Ltd</general><scope>FBQ</scope><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>K9.</scope><scope>7X8</scope></search><sort><creationdate>200405</creationdate><title>Melanin-concentrating hormone receptor mutations and human obesity: functional analysis</title><author>Gibson, W.T ; Pissios, P ; Trombly, D.J ; Luan, J ; Keogh, J ; Wareham, N.J ; Maratos-Flier, E ; O'Rahilly, S ; Farooqi, I.S</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4681-3f922c3b280944fe2a620d61b3ce5afc055b2687c8e9f7498dd314c9319609ba3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Amino Acid Sequence</topic><topic>association study</topic><topic>Base Sequence</topic><topic>ERK phosphorylation</topic><topic>GTP-Binding Proteins - physiology</topic><topic>G‐protein‐coupled receptors</topic><topic>Humans</topic><topic>Hyperphagia - genetics</topic><topic>Linkage Disequilibrium</topic><topic>MCHR1</topic><topic>MCHR2</topic><topic>Mitogen-Activated Protein Kinases - metabolism</topic><topic>Molecular Sequence Data</topic><topic>Mutation</topic><topic>Obesity - genetics</topic><topic>Phosphorylation</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Receptors, G-Protein-Coupled</topic><topic>Receptors, Pituitary Hormone - chemistry</topic><topic>Receptors, Pituitary Hormone - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Gibson, W.T</creatorcontrib><creatorcontrib>Pissios, P</creatorcontrib><creatorcontrib>Trombly, D.J</creatorcontrib><creatorcontrib>Luan, J</creatorcontrib><creatorcontrib>Keogh, J</creatorcontrib><creatorcontrib>Wareham, N.J</creatorcontrib><creatorcontrib>Maratos-Flier, E</creatorcontrib><creatorcontrib>O'Rahilly, S</creatorcontrib><creatorcontrib>Farooqi, I.S</creatorcontrib><collection>AGRIS</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><jtitle>Obesity (Silver Spring, Md.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gibson, W.T</au><au>Pissios, P</au><au>Trombly, D.J</au><au>Luan, J</au><au>Keogh, J</au><au>Wareham, N.J</au><au>Maratos-Flier, E</au><au>O'Rahilly, S</au><au>Farooqi, I.S</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Melanin-concentrating hormone receptor mutations and human obesity: functional analysis</atitle><jtitle>Obesity (Silver Spring, Md.)</jtitle><addtitle>Obes Res</addtitle><date>2004-05</date><risdate>2004</risdate><volume>12</volume><issue>5</issue><spage>743</spage><epage>749</epage><pages>743-749</pages><issn>1071-7323</issn><issn>1930-7381</issn><eissn>1550-8528</eissn><eissn>1930-739X</eissn><abstract>Melanin‐concentrating hormone (MCH), a neuropeptide highly expressed in the lateral hypothalamus, has an important role in the regulation of energy balance and body weight in rodents. We examined whether mutations in the two known MCH receptors might be associated with obesity‐related phenotypes in humans. Among 106 subjects with severe early onset obesity and a history of hyperphagia, we found two missense variants in MCHR1: Y181H and R248Q. Neither of these was found in 192 normal weight controls. R248Q cosegregated with obesity across two generations; family data were unavailable for Y181H. When expressed in HEK293 cells, R248Q showed no evidence of constitutive activation or ligand hypersensitivity for extracellular signal‐regulated kinase phosphorylation. In addition, R248Q showed no enhanced suppression of cAMP generation. Two common single‐nucleotide polymorphisms were found to be in linkage disequilibrium: g.‐114A>G and c.39C>T. No association between either of these single‐nucleotide polymorphisms and obesity‐related phenotypes was found among a population cohort of 541 whites. Only two rare noncoding variants were found in MCHR2. In conclusion, mutations in the MCH receptors are not commonly found in humans with severe early onset obesity. Clarification of the relationship of these variants to obesity must await study in other populations and/or in genetically modified mice.</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>15166293</pmid><doi>10.1038/oby.2004.89</doi><tpages>7</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1071-7323 |
| ispartof | Obesity (Silver Spring, Md.), 2004-05, Vol.12 (5), p.743-749 |
| issn | 1071-7323 1930-7381 1550-8528 1930-739X |
| language | eng |
| recordid | cdi_proquest_miscellaneous_71967263 |
| source | MEDLINE; Wiley Online Library Journals Frontfile Complete; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Wiley Free Content |
| subjects | Amino Acid Sequence association study Base Sequence ERK phosphorylation GTP-Binding Proteins - physiology G‐protein‐coupled receptors Humans Hyperphagia - genetics Linkage Disequilibrium MCHR1 MCHR2 Mitogen-Activated Protein Kinases - metabolism Molecular Sequence Data Mutation Obesity - genetics Phosphorylation Polymorphism, Single Nucleotide Receptors, G-Protein-Coupled Receptors, Pituitary Hormone - chemistry Receptors, Pituitary Hormone - genetics |
| title | Melanin-concentrating hormone receptor mutations and human obesity: functional analysis |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-16T12%3A17%3A51IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Melanin-concentrating%20hormone%20receptor%20mutations%20and%20human%20obesity:%20functional%20analysis&rft.jtitle=Obesity%20(Silver%20Spring,%20Md.)&rft.au=Gibson,%20W.T&rft.date=2004-05&rft.volume=12&rft.issue=5&rft.spage=743&rft.epage=749&rft.pages=743-749&rft.issn=1071-7323&rft.eissn=1550-8528&rft_id=info:doi/10.1038/oby.2004.89&rft_dat=%3Cproquest_cross%3E2726966581%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1030788478&rft_id=info:pmid/15166293&rfr_iscdi=true |