Prediction of non-alcoholic fatty-liver disease and liver fat content by serum molecular lipids

Matej Orešič, Tuulia Hyötyläinen, Anna Kotronen, Peddinti Gopalacharyulu, Heli Nygren, Johanna Arola, Sandra Castillo, Ismo Mattila, Antti Hakkarainen, Ronald J.H. Borra, Miikka Juhani Honka, An Verrijken, Sven Francque, Patricia Iozzo, Marja Leivonen, Nabil Jaser, Anne Juuti, Thorkild I.A. Sørensen, Pirjo Nuutila, Luc Van GaalHannele Yki-Järvinen

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Abstract

Aims/hypothesis: We examined whether analysis of lipids by ultra-performance liquid chromatography (UPLC) coupled to MS allows the development of a laboratory test for non-alcoholic fatty-liver disease (NAFLD), and how a lipid-profile biomarker compares with the prediction of NAFLD and liver-fat content based on routinely available clinical and laboratory data. Methods: We analysed the concentrations of molecular lipids by UPLC-MS in blood samples of 679 well-characterised individuals in whom liver-fat content was measured using proton magnetic resonance spectroscopy (1H-MRS) or liver biopsy. The participants were divided into biomarker-discovery (n = 287) and validation (n = 392) groups to build and validate the diagnostic models, respectively. Results: Individuals with NAFLD had increased triacylglycerols with low carbon number and double-bond content while lysophosphatidylcholines and ether phospholipids were diminished in those with NAFLD. A serum-lipid signature comprising three molecular lipids ('lipid triplet') was developed to estimate the percentage of liver fat. It had a sensitivity of 69.1% and specificity of 73.8% when applied for diagnosis of NAFLD in the validation series. The usefulness of the lipid triplet was demonstrated in a weight-loss intervention study. Conclusions/interpretation: The liver-fat-biomarker signature based on molecular lipids may provide a non-invasive tool to diagnose NAFLD, in addition to highlighting lipid molecular pathways involved in the disease.

Original languageEnglish
Pages (from-to)2266-2274
Number of pages9
JournalDiabetologia
Volume56
Issue number10
DOIs
Publication statusPublished - 1 Oct 2013
MoE publication typeNot Eligible

Keywords

  • Lipidomics
  • Mass spectrometry
  • Non-alcoholic fatty-liver disease

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    Orešič, M., Hyötyläinen, T., Kotronen, A., Gopalacharyulu, P., Nygren, H., Arola, J., Castillo, S., Mattila, I., Hakkarainen, A., Borra, R. J. H., Honka, M. J., Verrijken, A., Francque, S., Iozzo, P., Leivonen, M., Jaser, N., Juuti, A., Sørensen, T. I. A., Nuutila, P., ... Yki-Järvinen, H. (2013). Prediction of non-alcoholic fatty-liver disease and liver fat content by serum molecular lipids. Diabetologia, 56(10), 2266-2274. https://doi.org/10.1007/s00125-013-2981-2