Human neuropeptide Y signal peptide gain-of-function polymorphism is associated with increased body mass index: possible mode of function
Neuropeptide Y (NPY) has been implicated in the control of food intake and energy balance based on many observations in animals. We have studied single nucleotide polymorphisms (SNPs) within the regulatory and coding sequences of the human NPY gene. One variant (1128 T>C), which causes an amino a...
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| Veröffentlicht in: | Regulatory peptides 2005-04, Vol.127 (1), p.45-53 |
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| creator | Ding, Bo Kull, Björn Liu, Zhurong Mottagui-Tabar, Salim Thonberg, Håkan Gu, Harvest F. Brookes, Anthony J. Grundemar, Lars Karlsson, Christina Hamsten, Anders Arner, Peter Östenson, Claes-Göran Efendic, Suad Monné, Magnus von Heijne, Gunnar Eriksson, Per Wahlestedt, Claes |
| description | Neuropeptide Y (NPY) has been implicated in the control of food intake and energy balance based on many observations in animals. We have studied single nucleotide polymorphisms (SNPs) within the regulatory and coding sequences of the human
NPY gene. One variant (1128 T>C), which causes an amino acid change from leucine to proline at codon 7 in the signal peptide of NPY, was associated with increased body mass index (BMI) in two separate Swedish populations of normal and overweight individuals. In vitro transcription and translation studies indicated the unlikelihood that this signal peptide variation affects the site of cleavage and targeting or uptake of NPY into the endoplasmic reticulum (ER). However, the mutant, and to a lesser extent the wild-type, signal peptide by themselves markedly potentiated NPY-induced food intake, as well as hypothalamic NPY receptor signaling. Our findings in humans strongly indicate that the NPY signaling system is implicated in body weight regulation and suggest a new and unexpected functional role of a signal peptide. |
| doi_str_mv | 10.1016/j.regpep.2004.10.011 |
| format | Article |
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NPY gene. One variant (1128 T>C), which causes an amino acid change from leucine to proline at codon 7 in the signal peptide of NPY, was associated with increased body mass index (BMI) in two separate Swedish populations of normal and overweight individuals. In vitro transcription and translation studies indicated the unlikelihood that this signal peptide variation affects the site of cleavage and targeting or uptake of NPY into the endoplasmic reticulum (ER). However, the mutant, and to a lesser extent the wild-type, signal peptide by themselves markedly potentiated NPY-induced food intake, as well as hypothalamic NPY receptor signaling. Our findings in humans strongly indicate that the NPY signaling system is implicated in body weight regulation and suggest a new and unexpected functional role of a signal peptide.</description><identifier>ISSN: 0167-0115</identifier><identifier>EISSN: 1873-1686</identifier><identifier>DOI: 10.1016/j.regpep.2004.10.011</identifier><identifier>PMID: 15680469</identifier><identifier>CODEN: REPPDY</identifier><language>eng</language><publisher>Shannon: Elsevier B.V</publisher><subject>Animals ; Association ; Biological and medical sciences ; Body Mass Index ; DNA Mutational Analysis ; Dose-Response Relationship, Drug ; Eating ; Endoplasmic Reticulum - metabolism ; Function ; Fundamental and applied biological sciences. Psychology ; Humans ; Male ; Medical sciences ; Metabolic diseases ; Middle Aged ; Molecular Sequence Data ; Neuropeptide Y ; Neuropeptide Y - administration & dosage ; Neuropeptide Y - metabolism ; Neuropeptide Y/administration & dosage/metabolism ; Obesity ; Polymorphism ; Polymorphism, Genetic ; Protein Binding ; Protein Sorting Signals - genetics ; Rats ; Rats, Sprague-Dawley ; Recombinant Fusion Proteins - metabolism ; Signal Transduction - physiology ; Sweden ; Vertebrates: endocrinology</subject><ispartof>Regulatory peptides, 2005-04, Vol.127 (1), p.45-53</ispartof><rights>2004 Elsevier B.V.</rights><rights>2005 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c510t-3b4147d9bf22e03863b22d0470bcfdf81f47daaec910fca386c5f168e477c5dd3</citedby><cites>FETCH-LOGICAL-c510t-3b4147d9bf22e03863b22d0470bcfdf81f47daaec910fca386c5f168e477c5dd3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0167011504003921$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,550,776,780,881,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=16474849$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15680469$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-18985$$DView record from Swedish Publication Index$$Hfree_for_read</backlink><backlink>$$Uhttp://kipublications.ki.se/Default.aspx?queryparsed=id:1957300$$DView record from Swedish Publication Index$$Hfree_for_read</backlink></links><search><creatorcontrib>Ding, Bo</creatorcontrib><creatorcontrib>Kull, Björn</creatorcontrib><creatorcontrib>Liu, Zhurong</creatorcontrib><creatorcontrib>Mottagui-Tabar, Salim</creatorcontrib><creatorcontrib>Thonberg, Håkan</creatorcontrib><creatorcontrib>Gu, Harvest F.</creatorcontrib><creatorcontrib>Brookes, Anthony J.</creatorcontrib><creatorcontrib>Grundemar, Lars</creatorcontrib><creatorcontrib>Karlsson, Christina</creatorcontrib><creatorcontrib>Hamsten, Anders</creatorcontrib><creatorcontrib>Arner, Peter</creatorcontrib><creatorcontrib>Östenson, Claes-Göran</creatorcontrib><creatorcontrib>Efendic, Suad</creatorcontrib><creatorcontrib>Monné, Magnus</creatorcontrib><creatorcontrib>von Heijne, Gunnar</creatorcontrib><creatorcontrib>Eriksson, Per</creatorcontrib><creatorcontrib>Wahlestedt, Claes</creatorcontrib><title>Human neuropeptide Y signal peptide gain-of-function polymorphism is associated with increased body mass index: possible mode of function</title><title>Regulatory peptides</title><addtitle>Regul Pept</addtitle><description>Neuropeptide Y (NPY) has been implicated in the control of food intake and energy balance based on many observations in animals. We have studied single nucleotide polymorphisms (SNPs) within the regulatory and coding sequences of the human
NPY gene. One variant (1128 T>C), which causes an amino acid change from leucine to proline at codon 7 in the signal peptide of NPY, was associated with increased body mass index (BMI) in two separate Swedish populations of normal and overweight individuals. In vitro transcription and translation studies indicated the unlikelihood that this signal peptide variation affects the site of cleavage and targeting or uptake of NPY into the endoplasmic reticulum (ER). However, the mutant, and to a lesser extent the wild-type, signal peptide by themselves markedly potentiated NPY-induced food intake, as well as hypothalamic NPY receptor signaling. Our findings in humans strongly indicate that the NPY signaling system is implicated in body weight regulation and suggest a new and unexpected functional role of a signal peptide.</description><subject>Animals</subject><subject>Association</subject><subject>Biological and medical sciences</subject><subject>Body Mass Index</subject><subject>DNA Mutational Analysis</subject><subject>Dose-Response Relationship, Drug</subject><subject>Eating</subject><subject>Endoplasmic Reticulum - metabolism</subject><subject>Function</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Humans</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Metabolic diseases</subject><subject>Middle Aged</subject><subject>Molecular Sequence Data</subject><subject>Neuropeptide Y</subject><subject>Neuropeptide Y - administration & dosage</subject><subject>Neuropeptide Y - metabolism</subject><subject>Neuropeptide Y/administration & dosage/metabolism</subject><subject>Obesity</subject><subject>Polymorphism</subject><subject>Polymorphism, Genetic</subject><subject>Protein Binding</subject><subject>Protein Sorting Signals - genetics</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Recombinant Fusion Proteins - metabolism</subject><subject>Signal Transduction - physiology</subject><subject>Sweden</subject><subject>Vertebrates: endocrinology</subject><issn>0167-0115</issn><issn>1873-1686</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>D8T</sourceid><recordid>eNp9kcFu1DAURSMEokPhDxDyBjYog504icMCqSqFIlViA0isLMd-nnpI7GAnlPmE_jVvlJSuYGX7vvOurHuz7DmjW0ZZ_Wa_jbAbYdwWlHKUtpSxB9mGiabMWS3qh9kGsSZHuTrJnqS0p5RVTVM-zk5YVQvK63aT3V7Og_LEwxwDmk3OAPlOktt51ZM7Yaecz4PN7ez15IInY-gPQ4jjtUsDcYmolIJ2agJDbtx0TZzXEVTCZxfMgQw4R83A77e4mpLreiBDQOdgyZ3p0-yRVX2CZ-t5mn39cPHl_DK_-vzx0_nZVa4rRqe87DjjjWk7WxRAS1GXXVEYyhvaaWusYBanSoFuGbVaIaAri3kAbxpdGVOeZvnim25gnDs5RjeoeJBBOblKP_AGshJFUbXIv_4n_959O5Mh7mSaJROtqJB-tdBjDD9nSJMcXNLQ98pDmJOsm1K0VV0jyBdQR0wkgv1rzKg8Fiz3cilYHgs-qtgkrr1Y_eduAHO_tDaKwMsVUEmr3kbltUv3XM0bLviRe7dwgFn_chBl0g68BuMi6Ema4P7_kz8NB8op</recordid><startdate>20050415</startdate><enddate>20050415</enddate><creator>Ding, Bo</creator><creator>Kull, Björn</creator><creator>Liu, Zhurong</creator><creator>Mottagui-Tabar, Salim</creator><creator>Thonberg, Håkan</creator><creator>Gu, Harvest F.</creator><creator>Brookes, Anthony J.</creator><creator>Grundemar, Lars</creator><creator>Karlsson, Christina</creator><creator>Hamsten, Anders</creator><creator>Arner, Peter</creator><creator>Östenson, Claes-Göran</creator><creator>Efendic, Suad</creator><creator>Monné, Magnus</creator><creator>von Heijne, Gunnar</creator><creator>Eriksson, Per</creator><creator>Wahlestedt, Claes</creator><general>Elsevier B.V</general><general>Elsevier</general><scope>IQODW</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>7X8</scope><scope>ADTPV</scope><scope>AOWAS</scope><scope>DG7</scope><scope>D8T</scope><scope>ZZAVC</scope></search><sort><creationdate>20050415</creationdate><title>Human neuropeptide Y signal peptide gain-of-function polymorphism is associated with increased body mass index: possible mode of function</title><author>Ding, Bo ; Kull, Björn ; Liu, Zhurong ; Mottagui-Tabar, Salim ; Thonberg, Håkan ; Gu, Harvest F. ; Brookes, Anthony J. ; Grundemar, Lars ; Karlsson, Christina ; Hamsten, Anders ; Arner, Peter ; Östenson, Claes-Göran ; Efendic, Suad ; Monné, Magnus ; von Heijne, Gunnar ; Eriksson, Per ; Wahlestedt, Claes</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c510t-3b4147d9bf22e03863b22d0470bcfdf81f47daaec910fca386c5f168e477c5dd3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Animals</topic><topic>Association</topic><topic>Biological and medical sciences</topic><topic>Body Mass Index</topic><topic>DNA Mutational Analysis</topic><topic>Dose-Response Relationship, Drug</topic><topic>Eating</topic><topic>Endoplasmic Reticulum - metabolism</topic><topic>Function</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Humans</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Metabolic diseases</topic><topic>Middle Aged</topic><topic>Molecular Sequence Data</topic><topic>Neuropeptide Y</topic><topic>Neuropeptide Y - administration & dosage</topic><topic>Neuropeptide Y - metabolism</topic><topic>Neuropeptide Y/administration & dosage/metabolism</topic><topic>Obesity</topic><topic>Polymorphism</topic><topic>Polymorphism, Genetic</topic><topic>Protein Binding</topic><topic>Protein Sorting Signals - genetics</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Recombinant Fusion Proteins - metabolism</topic><topic>Signal Transduction - physiology</topic><topic>Sweden</topic><topic>Vertebrates: endocrinology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ding, Bo</creatorcontrib><creatorcontrib>Kull, Björn</creatorcontrib><creatorcontrib>Liu, Zhurong</creatorcontrib><creatorcontrib>Mottagui-Tabar, Salim</creatorcontrib><creatorcontrib>Thonberg, Håkan</creatorcontrib><creatorcontrib>Gu, Harvest F.</creatorcontrib><creatorcontrib>Brookes, Anthony J.</creatorcontrib><creatorcontrib>Grundemar, Lars</creatorcontrib><creatorcontrib>Karlsson, Christina</creatorcontrib><creatorcontrib>Hamsten, Anders</creatorcontrib><creatorcontrib>Arner, Peter</creatorcontrib><creatorcontrib>Östenson, Claes-Göran</creatorcontrib><creatorcontrib>Efendic, Suad</creatorcontrib><creatorcontrib>Monné, Magnus</creatorcontrib><creatorcontrib>von Heijne, Gunnar</creatorcontrib><creatorcontrib>Eriksson, Per</creatorcontrib><creatorcontrib>Wahlestedt, Claes</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>SwePub</collection><collection>SwePub Articles</collection><collection>SWEPUB Stockholms universitet</collection><collection>SWEPUB Freely available online</collection><collection>SwePub Articles full text</collection><jtitle>Regulatory peptides</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ding, Bo</au><au>Kull, Björn</au><au>Liu, Zhurong</au><au>Mottagui-Tabar, Salim</au><au>Thonberg, Håkan</au><au>Gu, Harvest F.</au><au>Brookes, Anthony J.</au><au>Grundemar, Lars</au><au>Karlsson, Christina</au><au>Hamsten, Anders</au><au>Arner, Peter</au><au>Östenson, Claes-Göran</au><au>Efendic, Suad</au><au>Monné, Magnus</au><au>von Heijne, Gunnar</au><au>Eriksson, Per</au><au>Wahlestedt, Claes</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Human neuropeptide Y signal peptide gain-of-function polymorphism is associated with increased body mass index: possible mode of function</atitle><jtitle>Regulatory peptides</jtitle><addtitle>Regul Pept</addtitle><date>2005-04-15</date><risdate>2005</risdate><volume>127</volume><issue>1</issue><spage>45</spage><epage>53</epage><pages>45-53</pages><issn>0167-0115</issn><eissn>1873-1686</eissn><coden>REPPDY</coden><abstract>Neuropeptide Y (NPY) has been implicated in the control of food intake and energy balance based on many observations in animals. We have studied single nucleotide polymorphisms (SNPs) within the regulatory and coding sequences of the human
NPY gene. One variant (1128 T>C), which causes an amino acid change from leucine to proline at codon 7 in the signal peptide of NPY, was associated with increased body mass index (BMI) in two separate Swedish populations of normal and overweight individuals. In vitro transcription and translation studies indicated the unlikelihood that this signal peptide variation affects the site of cleavage and targeting or uptake of NPY into the endoplasmic reticulum (ER). However, the mutant, and to a lesser extent the wild-type, signal peptide by themselves markedly potentiated NPY-induced food intake, as well as hypothalamic NPY receptor signaling. Our findings in humans strongly indicate that the NPY signaling system is implicated in body weight regulation and suggest a new and unexpected functional role of a signal peptide.</abstract><cop>Shannon</cop><cop>Amsterdam</cop><pub>Elsevier B.V</pub><pmid>15680469</pmid><doi>10.1016/j.regpep.2004.10.011</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Association Biological and medical sciences Body Mass Index DNA Mutational Analysis Dose-Response Relationship, Drug Eating Endoplasmic Reticulum - metabolism Function Fundamental and applied biological sciences. Psychology Humans Male Medical sciences Metabolic diseases Middle Aged Molecular Sequence Data Neuropeptide Y Neuropeptide Y - administration & dosage Neuropeptide Y - metabolism Neuropeptide Y/administration & dosage/metabolism Obesity Polymorphism Polymorphism, Genetic Protein Binding Protein Sorting Signals - genetics Rats Rats, Sprague-Dawley Recombinant Fusion Proteins - metabolism Signal Transduction - physiology Sweden Vertebrates: endocrinology |
| title | Human neuropeptide Y signal peptide gain-of-function polymorphism is associated with increased body mass index: possible mode of function |
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