Metabolomic profiling can predict which humans will develop liver dysfunction when deprived of dietary choline.

TitleMetabolomic profiling can predict which humans will develop liver dysfunction when deprived of dietary choline.
Publication TypeJournal Article
Year of Publication2010
AuthorsSha W, da Costa K-A, Fischer LM, Milburn MV, Lawton KA, Berger A, Jia W, Zeisel SH
JournalFASEB J
Volume24
Issue8
Pagination2962-75
Date Published2010 Aug
ISSN1530-6860
KeywordsCholine, Choline Deficiency, Diet, Fats, Humans, Liver, Liver Diseases, Metabolomics, Predictive Value of Tests
Abstract

<p>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 > or = 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.</p>

DOI10.1096/fj.09-154054
Alternate JournalFASEB J.
PubMed ID20371621
PubMed Central IDPMC2909293
Grant ListP30 ES010126 / ES / NIEHS NIH HHS / United States
M01 RR000046 / RR / NCRR NIH HHS / United States
DK55865 / DK / NIDDK NIH HHS / United States
R01 DK055865 / DK / NIDDK NIH HHS / United States
DK56350 / DK / NIDDK NIH HHS / United States
P30 DK056350 / DK / NIDDK NIH HHS / United States
RR00046 / RR / NCRR NIH HHS / United States