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 Gaal & 1 others Hannele Yki-Järvinen

Research output: Contribution to journalArticleScientificpeer-review

52 Citations (Scopus)

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

Fingerprint

Fats
Lipids
Liver
Serum
Biomarkers
Liquid Chromatography
Phospholipid Ethers
Non-alcoholic Fatty Liver Disease
Lysophosphatidylcholines
Weight Loss
Triglycerides
Carbon
Biopsy
Sensitivity and Specificity

Keywords

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

Cite this

Orešič, M., Hyötyläinen, T., Kotronen, A., Gopalacharyulu, P., Nygren, H., Arola, J., ... 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
Orešič, Matej ; Hyötyläinen, Tuulia ; Kotronen, Anna ; Gopalacharyulu, Peddinti ; Nygren, Heli ; Arola, Johanna ; Castillo, Sandra ; Mattila, Ismo ; Hakkarainen, Antti ; Borra, Ronald J.H. ; Honka, Miikka Juhani ; Verrijken, An ; Francque, Sven ; Iozzo, Patricia ; Leivonen, Marja ; Jaser, Nabil ; Juuti, Anne ; Sørensen, Thorkild I.A. ; Nuutila, Pirjo ; Van Gaal, Luc ; Yki-Järvinen, Hannele. / Prediction of non-alcoholic fatty-liver disease and liver fat content by serum molecular lipids. In: Diabetologia. 2013 ; Vol. 56, No. 10. pp. 2266-2274.
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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.",
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Orešič, M, Hyötyläinen, T, Kotronen, A, Gopalacharyulu, P, Nygren, H, Arola, J, Castillo, S, Mattila, I, Hakkarainen, A, Borra, RJH, Honka, MJ, Verrijken, A, Francque, S, Iozzo, P, Leivonen, M, Jaser, N, Juuti, A, Sørensen, TIA, Nuutila, P, Van Gaal, L & Yki-Järvinen, H 2013, 'Prediction of non-alcoholic fatty-liver disease and liver fat content by serum molecular lipids', Diabetologia, vol. 56, no. 10, pp. 2266-2274. https://doi.org/10.1007/s00125-013-2981-2

Prediction of non-alcoholic fatty-liver disease and liver fat content by serum molecular lipids. / Orešič, Matej; Hyötyläinen, Tuulia; Kotronen, Anna; Gopalacharyulu, Peddinti; Nygren, Heli; Arola, Johanna; Castillo, Sandra; Mattila, Ismo; Hakkarainen, Antti; Borra, Ronald J.H.; Honka, Miikka Juhani; Verrijken, An; Francque, Sven; Iozzo, Patricia; Leivonen, Marja; Jaser, Nabil; Juuti, Anne; Sørensen, Thorkild I.A.; Nuutila, Pirjo; Van Gaal, Luc; Yki-Järvinen, Hannele.

In: Diabetologia, Vol. 56, No. 10, 01.10.2013, p. 2266-2274.

Research output: Contribution to journalArticleScientificpeer-review

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T1 - Prediction of non-alcoholic fatty-liver disease and liver fat content by serum molecular lipids

AU - Orešič, Matej

AU - Hyötyläinen, Tuulia

AU - Kotronen, Anna

AU - Gopalacharyulu, Peddinti

AU - Nygren, Heli

AU - Arola, Johanna

AU - Castillo, Sandra

AU - Mattila, Ismo

AU - Hakkarainen, Antti

AU - Borra, Ronald J.H.

AU - Honka, Miikka Juhani

AU - Verrijken, An

AU - Francque, Sven

AU - Iozzo, Patricia

AU - Leivonen, Marja

AU - Jaser, Nabil

AU - Juuti, Anne

AU - Sørensen, Thorkild I.A.

AU - Nuutila, Pirjo

AU - Van Gaal, Luc

AU - Yki-Järvinen, Hannele

PY - 2013/10/1

Y1 - 2013/10/1

N2 - 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.

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KW - Lipidomics

KW - Mass spectrometry

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Orešič M, Hyötyläinen T, Kotronen A, Gopalacharyulu P, Nygren H, Arola J et al. Prediction of non-alcoholic fatty-liver disease and liver fat content by serum molecular lipids. Diabetologia. 2013 Oct 1;56(10):2266-2274. https://doi.org/10.1007/s00125-013-2981-2