Non-alcoholic fatty liver disease Stratification by Liver Lipidomics


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.


DOI: 10.1016/j.jlr.2021.100104

Projects: LiSyM Pillar I: Early Metabolic Injury (LiSyM-EMI)

Publication type: Journal

Journal: Journal of Lipid Research

Citation: Journal of Lipid Research:100104

Date Published: 1st Aug 2021

Registered Mode: by DOI

Authors: Olga Vvedenskaya, Tim Daniel Rose, Oskar Knittelfelder, Alessandra Palladini, Judith Andrea Heidrun Wodke, Kai Schumann, Jacobo Miranda Ackerman, Yuting Wang, Canan Has, Mario Brosch, Veera Raghavan Thangapandi, Stephan Buch, Thomas Züllig, Jürgen Hartler, Harald C. Köfeler, Christoph Röcken, Ünal Coskun, Edda Klipp, Witigo von Schoenfels, Justus Gross, Clemens Schafmayer, Jochen Hampe, Josch Konstantin Pauling, Andrej Shevchenko

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Vvedenskaya, O., Rose, T. D., Knittelfelder, O., Palladini, A., Wodke, J. A. H., Schuhmann, 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., … Shevchenko, A. (2021). Nonalcoholic fatty liver disease stratification by liver lipidomics. In Journal of Lipid Research (Vol. 62, p. 100104). Elsevier BV.

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Created: 14th Aug 2021 at 18:44

Last updated: 8th Mar 2024 at 07:44

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