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
Hauptverfasser: Sha, Wei, da Costa, Kerry-Ann, Fischer, Leslie M, Milburn, Michael V, Lawton, Kay A, Berger, Alvin, Jia, Wei, Zeisel, Steven H
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container_end_page 2975
container_issue 8
container_start_page 2962
container_title The FASEB journal
container_volume 24
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 &lt;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. 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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 &lt;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. 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Metabolomic profiling can predict which humans will develop liver dysfunction when deprived of dietary choline.</description><subject>Choline - administration &amp; 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 &amp; 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. 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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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