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
    
 
    
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        Sprache
        englisch
    
 
    
        Veröffentlichungsjahr
        2021
    
 
    
        Prepublished im Jahr 
        
    
 
    
        HGF-Berichtsjahr
        2021
    
 
    
    
        ISSN (print) / ISBN
        0022-2275
    
 
    
        e-ISSN
        1539-7262
    
 
    
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	    Band: 62,  
	    Heft: ,  
	    Seiten: ,  
	    Artikelnummer: 100104 
	    Supplement: ,  
	
    
 
  
        
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            Verlag
            American Society for Biochemistry and Molecular Biology
        
 
        
            Verlagsort
            Radarweg 29, 1043 Nx Amsterdam, Netherlands
        
 
	
        
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        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
    
 
    
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        Erfassungsdatum
        2021-10-06