title: Circulating lysophosphatidylcholines are markers of a metabolically benign nonalcoholic fatty liver.
abstract: OBJECTIVE
  Nonalcoholic fatty liver (NAFL) is thought to contribute to insulin resistance and its metabolic complications. However, some individuals with NAFL remain insulin sensitive. Mechanisms involved in the susceptibility to develop insulin resistance in humans with NAFL are largely unknown. We investigated circulating markers and mechanisms of a metabolically benign and malignant NAFL by applying a metabolomic approach.
  
  
  METHODS
  A total of 265 metabolites were analyzed before and after a 9-month lifestyle intervention in plasma from 20 insulin-sensitive and 20 insulin-resistant subjects with NAFL. The relevant plasma metabolites were then tested for relationships with insulin sensitivity in 17 subjects without NAFL and in plasma from 29 subjects with liver tissue samples.
  
  
  RESULTS
  The best separation of the insulin-sensitive from the insulin-resistant NAFL group was achieved by a metabolite pattern including the branched-chain amino acids leucine and isoleucine, ornithine, the acylcarnitines C3:0-, C16:0-, and C18:0-carnitine, and lysophosphatidylcholine (lyso-PC) C16:0 (area under the ROC curve, 0.77 [P = 0.00023] at baseline and 0.80 [P = 0.000019] at follow-up). Among the individual metabolites, predominantly higher levels of lyso-PC C16:0, both at baseline (P = 0.0039) and at follow-up (P = 0.001), were found in the insulin-sensitive compared with the insulin-resistant subjects. In the non-NAFL groups, no differences in lyso-PC C16:0 levels were found between the insulin-sensitive and insulin-resistant subjects, and these relationships were replicated in plasma from subjects with liver tissue samples.
  
  
  CONCLUSIONS
  From a plasma metabolomic pattern, particularly lyso-PCs are able to separate metabolically benign from malignant NAFL in humans and may highlight important pathways in the pathogenesis of fatty liver-induced insulin resistance.
authors.affiliation: Division of Endocrinology, Department of Internal Medicine, University Hospital Tübingen, Tübingen, Germany.
authors.forename: Rainer
authors.initials: R
authors.lastname: Lehmann
authors.forename: Holger
authors.initials: H
authors.lastname: Franken
authors.forename: Sascha
authors.initials: S
authors.lastname: Dammeier
authors.forename: Lars
authors.initials: L
authors.lastname: Rosenbaum
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Kantartzis
authors.forename: Andreas
authors.initials: A
authors.lastname: Peter
authors.forename: Andreas
authors.initials: A
authors.lastname: Zell
authors.forename: Patrick
authors.initials: P
authors.lastname: Adam
authors.forename: Jia
authors.initials: J
authors.lastname: Li
authors.forename: Guowang
authors.initials: G
authors.lastname: Xu
authors.forename: Alfred
authors.initials: A
authors.lastname: Königsrainer
authors.forename: Jürgen
authors.initials: J
authors.lastname: Machann
authors.forename: Fritz
authors.initials: F
authors.lastname: Schick
authors.forename: Martin
authors.initials: M
authors.lastname: Hrabé de Angelis
authors.forename: Matthias
authors.initials: M
authors.lastname: Schwab
authors.forename: Harald
authors.initials: H
authors.lastname: Staiger
authors.forename: Erwin
authors.initials: E
authors.lastname: Schleicher
authors.forename: Amalia
authors.initials: A
authors.lastname: Gastaldelli
authors.forename: Andreas
authors.initials: A
authors.lastname: Fritsche
authors.forename: Hans-Ulrich
authors.initials: HU
authors.lastname: Häring
authors.forename: Norbert
authors.initials: N
authors.lastname: Stefan
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood*; D005234:Fatty Liver / Q000097:blood* / Q000503:physiopathology; D005260:Female; D006801:Humans; D007333:Insulin Resistance; D008099:Liver / Q000378:metabolism; D008244:Lysophosphatidylcholines / Q000097:blood*; D008297:Male; D055432:Metabolomics; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease
chemical_list: D015415:Biomarkers; D008244:Lysophosphatidylcholines