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Vvedenskaya, O.* ; Rose, T.D.* ; Knittelfelder, O.* ; Palladini, A. ; Wodke, J.A.H.* ; Schumann, K.* ; Ackerman, J.M.* ; Wang, Y.* ; Has, C.* ; Brosch, M.* ; Thangapandi, V.R.* ; Buch, S.* ; Züllig, T.* ; Hartler, J.* ; Köfeler, H.C.* ; Röcken, C.* ; Coskun, Ü. ; Klipp, E.* ; von Schoenfels, W.* ; Gross, J.* ; Schafmayer, C.* ; Hampe, J.* ; Pauling, J.K.* ; Shevchenko, A.*

Non-alcoholic fatty liver disease Stratification by Liver Lipidomics.

J. Lipid Res. 62:100104 (2021)

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Non-alcoholic fatty liver disease (NAFLD) is a common metabolic dysfunction leading to hepatic steatosis. However, NAFLD's global impact on the liver lipidome is poorly understood. Using high-resolution shotgun mass spectrometry, we quantified the molar abundance of 316 species from 22 major lipid classes in liver biopsies of 365 patients, including non-steatotic patients with normal or excessive weight, patients diagnosed with NAFL (non-alcoholic fatty liver) or NASH (non-alcoholic steatohepatitis), and patients bearing common mutations of NAFLD-related protein factors. We confirmed the progressive accumulation of di- and tri- acylglycerols and cholesteryl esters in the liver of NAFL and NASH patients, while the bulk composition of glycerophospho- and sphingolipids remained unchanged. Further stratification by biclustering analysis identified sphingomyelin species comprising n24:2 fatty acid moieties as membrane lipid markers of NAFLD. Normalized relative abundance of sphingomyelins SM 43:3;2 and SM 43:1;2 containing n24:2 and n24:0 fatty acid moieties, respectively, showed opposite trends during NAFLD progression and distinguished NAFL and NASH lipidomes from the lipidome of non-steatoic livers. Together with several glycerophospholipids containing a C22:6 fatty acid moiety, these lipids serve as markers of early and advanced stages of NAFL.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Nafl ; Nafld ; Nash ; Biclustering Analysis ; Lipid Biomarkers ; Liver Biopsies ; Liver Lipidome ; Shotgun Lipidomics ; Sphingomyelins ; Steatosis; De-novo Lipogenesis; Shotgun Lipidomics; Mass-spectrometry; Blood-plasma; Resolution; Pnpla3; Sphingolipids; Mboat7; Derivatization; Identification

ISSN (print) / ISBN 0022-2275

e-ISSN 1539-7262

Journal Journal of Lipid Research

Quellenangaben Volume: 62, Article Number: 100104

Publisher American Society for Biochemistry and Molecular Biology

Publishing Place Radarweg 29, 1043 Nx Amsterdam, Netherlands

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute for Pancreatic Beta Cell Research (IPI)

Grants Deutsche Forschungsgemeinschaft (DFG)
University of Graz
HRSM project "Explorative Lipidomics seltener und chronischer Krankheiten''
Austrian Federal Ministry of Education, Science and Research
Bavarian State Ministry of Science and the Arts
German Federal Ministry of Education and Research (BMBF)
Lipidomics and Informatics for Life Sciences (LIFS) unit of de.nBi consortium
German Ministry of Research and Education (BmBF) through the Liver Systems Medicine (LiSyM) network grant