Metabolomic profiling can predict which humans will develop liver dysfunction when deprived of dietary choline
Choline is an essential nutrient, and deficiency causes liver and muscle dysfunction. Common genetic variations alter the risk of developing organ dysfunction when choline deficient, probably by causing metabolic inefficiencies that should be detectable even while ingesting a normal choline-adequate...
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Veröffentlicht in: | The FASEB journal 2010-08, Vol.24 (8), p.2962-2975 |
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creator | Sha, Wei da Costa, Kerry-Ann Fischer, Leslie M Milburn, Michael V Lawton, Kay A Berger, Alvin Jia, Wei Zeisel, Steven H |
description | Choline is an essential nutrient, and deficiency causes liver and muscle dysfunction. Common genetic variations alter the risk of developing organ dysfunction when choline deficient, probably by causing metabolic inefficiencies that should be detectable even while ingesting a normal choline-adequate diet. We determined whether metabolomic profiling of plasma at baseline could predict whether humans will develop liver dysfunction when deprived of dietary choline. Fifty-three participants were fed a diet containing 550 mg choline/70 kg/d for 10 d and then fed |
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Common genetic variations alter the risk of developing organ dysfunction when choline deficient, probably by causing metabolic inefficiencies that should be detectable even while ingesting a normal choline-adequate diet. We determined whether metabolomic profiling of plasma at baseline could predict whether humans will develop liver dysfunction when deprived of dietary choline. Fifty-three participants were fed a diet containing 550 mg choline/70 kg/d for 10 d and then fed <50 mg choline/70 kg/d for up to 42 d. Participants who developed organ dysfunction on this diet were repleted with a choline-adequate diet for ≥3 d. Plasma samples, obtained at baseline, end of depletion, and end of repletion, were used for targeted and nontargeted metabolomic profiling. Liver fat was assessed using magnetic resonance spectroscopy. Metabolomic profiling and targeted biochemical analyses were highly correlated for the analytes assessed by both procedures. In addition, we report relative concentration changes of other small molecules detected by the nontargeted metabolomic analysis after choline depletion. Finally, we show that metabolomic profiles of participants when they were consuming a control baseline diet could predict whether they would develop liver dysfunction when deprived of dietary choline.--Sha, W., da Costa, K., Fischer, L. M., Milburn, M. V., Lawton, K. A., Berger, A., Jia, W., Zeisel, S. H. Metabolomic profiling can predict which humans will develop liver dysfunction when deprived of dietary choline.</description><identifier>ISSN: 0892-6638</identifier><identifier>EISSN: 1530-6860</identifier><identifier>DOI: 10.1096/fj.09-154054</identifier><identifier>PMID: 20371621</identifier><language>eng</language><publisher>United States: The Federation of American Societies for Experimental Biology</publisher><subject>Choline - administration & dosage ; Choline Deficiency - complications ; Diet ; Fats - analysis ; fatty liver ; Humans ; Liver - chemistry ; Liver Diseases - etiology ; metabolomics ; Metabolomics - methods ; PEMT ; plasma ; Predictive Value of Tests ; Research Communications</subject><ispartof>The FASEB journal, 2010-08, Vol.24 (8), p.2962-2975</ispartof><rights>FASEB</rights><rights>2010 FASEB 2010</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5224-e9c3a7f248164e16cb2b8553e13509b23c05c5e5e3d6f4fdd8dd205435761ba43</citedby><cites>FETCH-LOGICAL-c5224-e9c3a7f248164e16cb2b8553e13509b23c05c5e5e3d6f4fdd8dd205435761ba43</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1096%2Ffj.09-154054$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1096%2Ffj.09-154054$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>230,314,776,780,881,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20371621$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sha, Wei</creatorcontrib><creatorcontrib>da Costa, Kerry-Ann</creatorcontrib><creatorcontrib>Fischer, Leslie M</creatorcontrib><creatorcontrib>Milburn, Michael V</creatorcontrib><creatorcontrib>Lawton, Kay A</creatorcontrib><creatorcontrib>Berger, Alvin</creatorcontrib><creatorcontrib>Jia, Wei</creatorcontrib><creatorcontrib>Zeisel, Steven H</creatorcontrib><title>Metabolomic profiling can predict which humans will develop liver dysfunction when deprived of dietary choline</title><title>The FASEB journal</title><addtitle>FASEB J</addtitle><description>Choline is an essential nutrient, and deficiency causes liver and muscle dysfunction. Common genetic variations alter the risk of developing organ dysfunction when choline deficient, probably by causing metabolic inefficiencies that should be detectable even while ingesting a normal choline-adequate diet. We determined whether metabolomic profiling of plasma at baseline could predict whether humans will develop liver dysfunction when deprived of dietary choline. Fifty-three participants were fed a diet containing 550 mg choline/70 kg/d for 10 d and then fed <50 mg choline/70 kg/d for up to 42 d. Participants who developed organ dysfunction on this diet were repleted with a choline-adequate diet for ≥3 d. Plasma samples, obtained at baseline, end of depletion, and end of repletion, were used for targeted and nontargeted metabolomic profiling. Liver fat was assessed using magnetic resonance spectroscopy. Metabolomic profiling and targeted biochemical analyses were highly correlated for the analytes assessed by both procedures. In addition, we report relative concentration changes of other small molecules detected by the nontargeted metabolomic analysis after choline depletion. Finally, we show that metabolomic profiles of participants when they were consuming a control baseline diet could predict whether they would develop liver dysfunction when deprived of dietary choline.--Sha, W., da Costa, K., Fischer, L. M., Milburn, M. V., Lawton, K. A., Berger, A., Jia, W., Zeisel, S. H. Metabolomic profiling can predict which humans will develop liver dysfunction when deprived of dietary choline.</description><subject>Choline - administration & dosage</subject><subject>Choline Deficiency - complications</subject><subject>Diet</subject><subject>Fats - analysis</subject><subject>fatty liver</subject><subject>Humans</subject><subject>Liver - chemistry</subject><subject>Liver Diseases - etiology</subject><subject>metabolomics</subject><subject>Metabolomics - methods</subject><subject>PEMT</subject><subject>plasma</subject><subject>Predictive Value of Tests</subject><subject>Research Communications</subject><issn>0892-6638</issn><issn>1530-6860</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kc1vFCEchonR2G315lm5eXEqHwMDF5PauH6kxkPtmTB87LBhYR1mttn_XpqpG714IuT38PDCC8ArjC4xkvy9314i2WDWItY-ASvMKGq44OgpWCEhScM5FWfgvJQtQggjzJ-DM4JohznBK5C-u0n3OeZdMHA_Zh9iSBtodKo7Z4OZ4P0QzACHeadTgfchRmjdwcW8hzEc3Ajtsfg5mSnkVFmX6ng_1omF2UMbqn88QjPkKnYvwDOvY3EvH9cLcLf-9PP6S3Pz4_PX66ubxjBC2sZJQ3XnSSswbx3mpie9YIw6TBmSPaEGMcMcc9Ry33prhbWkvp-yjuNet_QCfFi8-7nfOWtcmkYdVc21q2lU1kH9O0lhUJt8UEQiSSStgrePgjH_ml2Z1C4U42LUyeW5qK4VkjLRkkq-W0gz5lJG50-3YKQeGlJ-q5BUS0MVf_13shP8p5IKiAWoX-2O_5Wp9e1Hsv6G5Mn9ZjnqdVZ6M4ai7m4JwhRh0THOOvobezWovQ</recordid><startdate>201008</startdate><enddate>201008</enddate><creator>Sha, Wei</creator><creator>da Costa, Kerry-Ann</creator><creator>Fischer, Leslie M</creator><creator>Milburn, Michael V</creator><creator>Lawton, Kay A</creator><creator>Berger, Alvin</creator><creator>Jia, Wei</creator><creator>Zeisel, Steven H</creator><general>The Federation of American Societies for Experimental Biology</general><general>Federation of American Societies for Experimental Biology</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>7X8</scope><scope>5PM</scope></search><sort><creationdate>201008</creationdate><title>Metabolomic profiling can predict which humans will develop liver dysfunction when deprived of dietary choline</title><author>Sha, Wei ; da Costa, Kerry-Ann ; Fischer, Leslie M ; Milburn, Michael V ; Lawton, Kay A ; Berger, Alvin ; Jia, Wei ; Zeisel, Steven H</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5224-e9c3a7f248164e16cb2b8553e13509b23c05c5e5e3d6f4fdd8dd205435761ba43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Choline - administration & dosage</topic><topic>Choline Deficiency - complications</topic><topic>Diet</topic><topic>Fats - analysis</topic><topic>fatty liver</topic><topic>Humans</topic><topic>Liver - chemistry</topic><topic>Liver Diseases - etiology</topic><topic>metabolomics</topic><topic>Metabolomics - methods</topic><topic>PEMT</topic><topic>plasma</topic><topic>Predictive Value of Tests</topic><topic>Research Communications</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sha, Wei</creatorcontrib><creatorcontrib>da Costa, Kerry-Ann</creatorcontrib><creatorcontrib>Fischer, Leslie M</creatorcontrib><creatorcontrib>Milburn, Michael V</creatorcontrib><creatorcontrib>Lawton, Kay A</creatorcontrib><creatorcontrib>Berger, Alvin</creatorcontrib><creatorcontrib>Jia, Wei</creatorcontrib><creatorcontrib>Zeisel, Steven H</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>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The FASEB journal</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sha, Wei</au><au>da Costa, Kerry-Ann</au><au>Fischer, Leslie M</au><au>Milburn, Michael V</au><au>Lawton, Kay A</au><au>Berger, Alvin</au><au>Jia, Wei</au><au>Zeisel, Steven H</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Metabolomic profiling can predict which humans will develop liver dysfunction when deprived of dietary choline</atitle><jtitle>The FASEB journal</jtitle><addtitle>FASEB J</addtitle><date>2010-08</date><risdate>2010</risdate><volume>24</volume><issue>8</issue><spage>2962</spage><epage>2975</epage><pages>2962-2975</pages><issn>0892-6638</issn><eissn>1530-6860</eissn><abstract>Choline is an essential nutrient, and deficiency causes liver and muscle dysfunction. Common genetic variations alter the risk of developing organ dysfunction when choline deficient, probably by causing metabolic inefficiencies that should be detectable even while ingesting a normal choline-adequate diet. We determined whether metabolomic profiling of plasma at baseline could predict whether humans will develop liver dysfunction when deprived of dietary choline. Fifty-three participants were fed a diet containing 550 mg choline/70 kg/d for 10 d and then fed <50 mg choline/70 kg/d for up to 42 d. Participants who developed organ dysfunction on this diet were repleted with a choline-adequate diet for ≥3 d. Plasma samples, obtained at baseline, end of depletion, and end of repletion, were used for targeted and nontargeted metabolomic profiling. Liver fat was assessed using magnetic resonance spectroscopy. Metabolomic profiling and targeted biochemical analyses were highly correlated for the analytes assessed by both procedures. In addition, we report relative concentration changes of other small molecules detected by the nontargeted metabolomic analysis after choline depletion. Finally, we show that metabolomic profiles of participants when they were consuming a control baseline diet could predict whether they would develop liver dysfunction when deprived of dietary choline.--Sha, W., da Costa, K., Fischer, L. M., Milburn, M. V., Lawton, K. A., Berger, A., Jia, W., Zeisel, S. H. Metabolomic profiling can predict which humans will develop liver dysfunction when deprived of dietary choline.</abstract><cop>United States</cop><pub>The Federation of American Societies for Experimental Biology</pub><pmid>20371621</pmid><doi>10.1096/fj.09-154054</doi><tpages>14</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Choline - administration & dosage Choline Deficiency - complications Diet Fats - analysis fatty liver Humans Liver - chemistry Liver Diseases - etiology metabolomics Metabolomics - methods PEMT plasma Predictive Value of Tests Research Communications |
title | Metabolomic profiling can predict which humans will develop liver dysfunction when deprived of dietary choline |
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