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)
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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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Typ der Hochschulschrift
Herausgeber
Schlagwörter
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
Keywords plus
Sprache
englisch
Veröffentlichungsjahr
2021
Prepublished im Jahr
HGF-Berichtsjahr
2021
ISSN (print) / ISBN
0022-2275
e-ISSN
1539-7262
ISBN
Bandtitel
Konferenztitel
Konferzenzdatum
Konferenzort
Konferenzband
Quellenangaben
Band: 62,
Heft: ,
Seiten: ,
Artikelnummer: 100104
Supplement: ,
Reihe
Verlag
American Society for Biochemistry and Molecular Biology
Verlagsort
Radarweg 29, 1043 Nx Amsterdam, Netherlands
Tag d. mündl. Prüfung
0000-00-00
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Prüfer
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Hochschule
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Veröffentlichungsdatum
0000-00-00
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0000-00-00
Anmelder/Inhaber
weitere Inhaber
Anmeldeland
Priorität
Begutachtungsstatus
Peer reviewed
Institut(e)
Institute of Pancreatic Islet Research (IPI)
POF Topic(s)
90000 - German Center for Diabetes Research
Forschungsfeld(er)
Helmholtz Diabetes Center
PSP-Element(e)
G-502600-002
Förderungen
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
Copyright
Erfassungsdatum
2021-10-06