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

Matej Oresic; Tuulia Hyotylainen; 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. Sorensen; Pirjo Nuutila; Luc Van Gaal; Hannele Yki-Jarvinen

doi:10.1007/s00125-013-2981-2

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

Matej Oresic^*, Tuulia Hyotylainen, 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. Sorensen, Pirjo Nuutila, Luc Van GaalHannele Yki-Jarvinen

^*Corresponding author for this work

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Abstract

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.

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 (H-1-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.

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.

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 language	English
Pages (from-to)	2266-2274
Number of pages	9
Journal	Diabetologia
Volume	56
Issue number	10
DOIs	https://doi.org/10.1007/s00125-013-2981-2
Publication status	Published - Oct-2013

Keywords

Lipidomics
Mass spectrometry
Non-alcoholic fatty-liver disease
HEPATIC STEATOSIS
INSULIN-RESISTANCE
MASS-SPECTROMETRY
CARDIOVASCULAR-DISEASE
GENERAL-POPULATION
METABOLIC SYNDROME
ACIDS
STEATOHEPATITIS
ACCUMULATION
MEN

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Oresic, M., Hyotylainen, 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., Sorensen, T. I. A., Nuutila, P., ... Yki-Jarvinen, 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

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title = "Prediction of non-alcoholic fatty-liver disease and liver fat content by serum molecular lipids",

abstract = "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.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 (H-1-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.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.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.",

keywords = "Lipidomics, Mass spectrometry, Non-alcoholic fatty-liver disease, HEPATIC STEATOSIS, INSULIN-RESISTANCE, MASS-SPECTROMETRY, CARDIOVASCULAR-DISEASE, GENERAL-POPULATION, METABOLIC SYNDROME, ACIDS, STEATOHEPATITIS, ACCUMULATION, MEN",

author = "Matej Oresic and Tuulia Hyotylainen and Anna Kotronen and Peddinti Gopalacharyulu and Heli Nygren and Johanna Arola and Sandra Castillo and Ismo Mattila and Antti Hakkarainen and Borra, {Ronald J. H.} and Miikka-Juhani Honka and An Verrijken and Sven Francque and Patricia Iozzo and Marja Leivonen and Nabil Jaser and Anne Juuti and Sorensen, {Thorkild I. A.} and Pirjo Nuutila and {Van Gaal}, Luc and Hannele Yki-Jarvinen",

year = "2013",

month = oct,

doi = "10.1007/s00125-013-2981-2",

language = "English",

volume = "56",

pages = "2266--2274",

journal = "Diabetologia",

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number = "10",

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Oresic, M, Hyotylainen, T, Kotronen, A, Gopalacharyulu, P, Nygren, H, Arola, J, Castillo, S, Mattila, I, Hakkarainen, A, Borra, RJH, Honka, M-J, Verrijken, A, Francque, S, Iozzo, P, Leivonen, M, Jaser, N, Juuti, A, Sorensen, TIA, Nuutila, P, Van Gaal, L & Yki-Jarvinen, 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

TY - JOUR

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

AU - Oresic, Matej

AU - Hyotylainen, 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 - Sorensen, Thorkild I. A.

AU - Nuutila, Pirjo

AU - Van Gaal, Luc

AU - Yki-Jarvinen, Hannele

PY - 2013/10

Y1 - 2013/10

N2 - 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.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 (H-1-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.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.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.

AB - 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.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 (H-1-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.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.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.

KW - Lipidomics

KW - Mass spectrometry

KW - Non-alcoholic fatty-liver disease

KW - HEPATIC STEATOSIS

KW - INSULIN-RESISTANCE

KW - MASS-SPECTROMETRY

KW - CARDIOVASCULAR-DISEASE

KW - GENERAL-POPULATION

KW - METABOLIC SYNDROME

KW - ACIDS

KW - STEATOHEPATITIS

KW - ACCUMULATION

KW - MEN

U2 - 10.1007/s00125-013-2981-2

DO - 10.1007/s00125-013-2981-2

M3 - Article

SN - 0012-186X

VL - 56

SP - 2266

EP - 2274

JO - Diabetologia

JF - Diabetologia

IS - 10

ER -

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

Abstract

Keywords

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