TY - JOUR
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.
AB - 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.
KW - Lipidomics
KW - Mass spectrometry
KW - Non-alcoholic fatty-liver disease
UR - http://www.scopus.com/inward/record.url?scp=84890116926&partnerID=8YFLogxK
U2 - 10.1007/s00125-013-2981-2
DO - 10.1007/s00125-013-2981-2
M3 - Article
C2 - 23824212
AN - SCOPUS:84890116926
SN - 0012-186X
VL - 56
SP - 2266
EP - 2274
JO - Diabetologia
JF - Diabetologia
IS - 10
ER -