title: Metabolomic profiling can predict which humans will develop liver dysfunction when deprived of dietary choline.
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 > 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.
authors.affiliation: Bioinformatics Research Center, University of North Carolina at Charlotte, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Sha
authors.forename: Kerry-Ann
authors.initials: KA
authors.lastname: da Costa
authors.forename: Leslie M
authors.initials: LM
authors.lastname: Fischer
authors.forename: Michael V
authors.initials: MV
authors.lastname: Milburn
authors.forename: Kay A
authors.initials: KA
authors.lastname: Lawton
authors.forename: Alvin
authors.initials: A
authors.lastname: Berger
authors.forename: Wei
authors.initials: W
authors.lastname: Jia
authors.forename: Steven H
authors.initials: SH
authors.lastname: Zeisel
mesh_terms: D002794:Choline / Q000008:administration & dosage; D002796:Choline Deficiency / Q000150:complications*; D004032:Diet; D005223:Fats / Q000032:analysis; D006801:Humans; D008099:Liver / Q000737:chemistry; D008107:Liver Diseases / Q000209:etiology*; D055432:Metabolomics / Q000379:methods*; D011237:Predictive Value of Tests
chemical_list: D005223:Fats; D002794:Choline