Role for the obesity-related FTO gene in the cellular sensing of amino acids
SNPs in the first intron of FTO (fat mass and obesity associated) are strongly associated with human obesity. While it is not yet formally established that this effect is mediated through the actions of the FTO protein itself, loss of function mutations in FTO or its murine homologue Fto result in s...
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| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 2013-02, Vol.110 (7), p.2557-2562 |
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| creator | Gulati, Pawan Cheung, Man Ka Antrobus, Robin Church, Chris D. Harding, Heather P. Tung, Yi-Chun Loraine Rimmington, Debra Ma, Marcella Ron, David Lehner, Paul J. Ashcroft, Frances M. Cox, Roger D. Coll, Anthony P. O'Rahilly, Stephen Yeo, Giles S. H. |
| description | SNPs in the first intron of FTO (fat mass and obesity associated) are strongly associated with human obesity. While it is not yet formally established that this effect is mediated through the actions of the FTO protein itself, loss of function mutations in FTO or its murine homologue Fto result in severe growth retardation, and mice globally overexpressing FTO are obese. The mechanisms through which FTO influences growth and body composition are unknown. We describe a role for FTO in the coupling of amino acid levels to mammalian target of rapamycin complex 1 signaling. These findings suggest that FTO may influence body composition through playing a role in cellular nutrient sensing. |
| doi_str_mv | 10.1073/pnas.1222796110 |
| format | Article |
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H.</creator><creatorcontrib>Gulati, Pawan ; Cheung, Man Ka ; Antrobus, Robin ; Church, Chris D. ; Harding, Heather P. ; Tung, Yi-Chun Loraine ; Rimmington, Debra ; Ma, Marcella ; Ron, David ; Lehner, Paul J. ; Ashcroft, Frances M. ; Cox, Roger D. ; Coll, Anthony P. ; O'Rahilly, Stephen ; Yeo, Giles S. H.</creatorcontrib><description>SNPs in the first intron of FTO (fat mass and obesity associated) are strongly associated with human obesity. While it is not yet formally established that this effect is mediated through the actions of the FTO protein itself, loss of function mutations in FTO or its murine homologue Fto result in severe growth retardation, and mice globally overexpressing FTO are obese. The mechanisms through which FTO influences growth and body composition are unknown. We describe a role for FTO in the coupling of amino acid levels to mammalian target of rapamycin complex 1 signaling. These findings suggest that FTO may influence body composition through playing a role in cellular nutrient sensing.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.1222796110</identifier><identifier>PMID: 23359686</identifier><language>eng</language><publisher>United States: National Academy of Sciences</publisher><subject>Alpha-Ketoglutarate-Dependent Dioxygenase FTO ; Amino acids ; Amino Acids - metabolism ; Animals ; Antibodies ; Biological Sciences ; body composition ; Body Composition - genetics ; Body fat ; Cell extracts ; Cell Fractionation ; Chromatography, Liquid ; Electrophoresis, Polyacrylamide Gel ; Fibroblasts ; Food intake ; Fractionation ; gene overexpression ; growth retardation ; HEK293 Cells ; Humans ; Immunoprecipitation ; introns ; Messenger RNA ; Mice ; Mutation ; Obesity ; Obesity - genetics ; Polymorphism, Single Nucleotide - genetics ; Proteins - genetics ; Proteins - metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Rodents ; Signal Transduction - genetics ; single nucleotide polymorphism ; Tandem Mass Spectrometry ; TOR Serine-Threonine Kinases - metabolism ; Transfection ; Western blotting</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 2013-02, Vol.110 (7), p.2557-2562</ispartof><rights>copyright © 1993-2008 National Academy of Sciences of the United States of America</rights><rights>Copyright National Academy of Sciences Feb 12, 2013</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c523t-10e79723754a40a447e0f651e77391b75458bb7b7953e76d8f430c5521313a233</citedby><cites>FETCH-LOGICAL-c523t-10e79723754a40a447e0f651e77391b75458bb7b7953e76d8f430c5521313a233</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/110/7.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/41992376$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/41992376$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,724,777,781,800,882,27905,27906,53772,53774,57998,58231</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23359686$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Gulati, Pawan</creatorcontrib><creatorcontrib>Cheung, Man Ka</creatorcontrib><creatorcontrib>Antrobus, Robin</creatorcontrib><creatorcontrib>Church, Chris D.</creatorcontrib><creatorcontrib>Harding, Heather P.</creatorcontrib><creatorcontrib>Tung, Yi-Chun Loraine</creatorcontrib><creatorcontrib>Rimmington, Debra</creatorcontrib><creatorcontrib>Ma, Marcella</creatorcontrib><creatorcontrib>Ron, David</creatorcontrib><creatorcontrib>Lehner, Paul J.</creatorcontrib><creatorcontrib>Ashcroft, Frances M.</creatorcontrib><creatorcontrib>Cox, Roger D.</creatorcontrib><creatorcontrib>Coll, Anthony P.</creatorcontrib><creatorcontrib>O'Rahilly, Stephen</creatorcontrib><creatorcontrib>Yeo, Giles S. H.</creatorcontrib><title>Role for the obesity-related FTO gene in the cellular sensing of amino acids</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>SNPs in the first intron of FTO (fat mass and obesity associated) are strongly associated with human obesity. While it is not yet formally established that this effect is mediated through the actions of the FTO protein itself, loss of function mutations in FTO or its murine homologue Fto result in severe growth retardation, and mice globally overexpressing FTO are obese. The mechanisms through which FTO influences growth and body composition are unknown. We describe a role for FTO in the coupling of amino acid levels to mammalian target of rapamycin complex 1 signaling. These findings suggest that FTO may influence body composition through playing a role in cellular nutrient sensing.</description><subject>Alpha-Ketoglutarate-Dependent Dioxygenase FTO</subject><subject>Amino acids</subject><subject>Amino Acids - metabolism</subject><subject>Animals</subject><subject>Antibodies</subject><subject>Biological Sciences</subject><subject>body composition</subject><subject>Body Composition - genetics</subject><subject>Body fat</subject><subject>Cell extracts</subject><subject>Cell Fractionation</subject><subject>Chromatography, Liquid</subject><subject>Electrophoresis, Polyacrylamide Gel</subject><subject>Fibroblasts</subject><subject>Food intake</subject><subject>Fractionation</subject><subject>gene overexpression</subject><subject>growth retardation</subject><subject>HEK293 Cells</subject><subject>Humans</subject><subject>Immunoprecipitation</subject><subject>introns</subject><subject>Messenger RNA</subject><subject>Mice</subject><subject>Mutation</subject><subject>Obesity</subject><subject>Obesity - genetics</subject><subject>Polymorphism, Single Nucleotide - genetics</subject><subject>Proteins - genetics</subject><subject>Proteins - metabolism</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>Rodents</subject><subject>Signal Transduction - genetics</subject><subject>single nucleotide polymorphism</subject><subject>Tandem Mass Spectrometry</subject><subject>TOR Serine-Threonine Kinases - metabolism</subject><subject>Transfection</subject><subject>Western blotting</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc1v1DAQxS0EotvCmRNgqRcuaWf8EduXSqiigLRSJWjPlpN1tlll7cVOkPrf43TLUrhwsuT3m6c38wh5g3CGoPj5Lrh8howxZWpEeEYWCAarWhh4ThYATFVaMHFEjnPeAICRGl6SI8a5NLWuF2T5LQ6edjHR8c7T2Pjcj_dV8oMb_Ype3VzTtQ-e9uFBb_0wTINLNPuQ-7CmsaNu24dIXduv8ivyonND9q8f3xNye_Xp5vJLtbz-_PXy47JqJeNjheCVUYwrKZwAJ4Ty0NUSvVLcYFO-pW4a1SgjuVf1SneCQyslQ47clewn5GLvu5uarV-1PozJDXaX-q1L9za63v6thP7OruNPy6UShkMx-PBokOKPyefRbvs8L-eCj1O2qIEjoubi_yjTSmstpSro6T_oJk4plEs8UKpGzutCne-pNsWck-8OuRHsXKqdS7V_Si0T756ue-B_t_gEmCcPdsVPWbZP9nYPbPIY04EQaEypYTZ4v9c7F61bpz7b2-8MsAZAgXVJ_QtrVbda</recordid><startdate>20130212</startdate><enddate>20130212</enddate><creator>Gulati, Pawan</creator><creator>Cheung, Man Ka</creator><creator>Antrobus, Robin</creator><creator>Church, Chris D.</creator><creator>Harding, Heather P.</creator><creator>Tung, Yi-Chun Loraine</creator><creator>Rimmington, Debra</creator><creator>Ma, Marcella</creator><creator>Ron, David</creator><creator>Lehner, Paul J.</creator><creator>Ashcroft, Frances M.</creator><creator>Cox, Roger D.</creator><creator>Coll, Anthony P.</creator><creator>O'Rahilly, Stephen</creator><creator>Yeo, Giles S. 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H.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Role for the obesity-related FTO gene in the cellular sensing of amino acids</atitle><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle><addtitle>Proc Natl Acad Sci U S A</addtitle><date>2013-02-12</date><risdate>2013</risdate><volume>110</volume><issue>7</issue><spage>2557</spage><epage>2562</epage><pages>2557-2562</pages><issn>0027-8424</issn><eissn>1091-6490</eissn><abstract>SNPs in the first intron of FTO (fat mass and obesity associated) are strongly associated with human obesity. While it is not yet formally established that this effect is mediated through the actions of the FTO protein itself, loss of function mutations in FTO or its murine homologue Fto result in severe growth retardation, and mice globally overexpressing FTO are obese. The mechanisms through which FTO influences growth and body composition are unknown. We describe a role for FTO in the coupling of amino acid levels to mammalian target of rapamycin complex 1 signaling. These findings suggest that FTO may influence body composition through playing a role in cellular nutrient sensing.</abstract><cop>United States</cop><pub>National Academy of Sciences</pub><pmid>23359686</pmid><doi>10.1073/pnas.1222796110</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Alpha-Ketoglutarate-Dependent Dioxygenase FTO Amino acids Amino Acids - metabolism Animals Antibodies Biological Sciences body composition Body Composition - genetics Body fat Cell extracts Cell Fractionation Chromatography, Liquid Electrophoresis, Polyacrylamide Gel Fibroblasts Food intake Fractionation gene overexpression growth retardation HEK293 Cells Humans Immunoprecipitation introns Messenger RNA Mice Mutation Obesity Obesity - genetics Polymorphism, Single Nucleotide - genetics Proteins - genetics Proteins - metabolism Reverse Transcriptase Polymerase Chain Reaction Rodents Signal Transduction - genetics single nucleotide polymorphism Tandem Mass Spectrometry TOR Serine-Threonine Kinases - metabolism Transfection Western blotting |
| title | Role for the obesity-related FTO gene in the cellular sensing of amino acids |
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