NAFLD Stratification by Liver Lipidomics

Abstract:

Non-alcoholic fatty liver disease (NAFLD) is a common metabolic dysfunction leading to hepatic steatosis, however its 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 or NASH and patients bearing common mutations of NAFLD-related protein factors. We confirmed the progressive accumulation of di- and tri- acylglycerols and cholesterol esters in the liver of NAFL and NASH patients, while the bulk composition of membrane lipid classes remained unchanged. Further stratification by biclustering analysis identified sphingomyelin species comprising n24:2 fatty acid moiety as membrane lipid markers of NAFLD. Normalized relative abundances of SM 43:3;2 and SM 43:1;2 showed opposite trends during NAFLD progression and distinguished NAFL and NASH lipidomes from the lipidome of non-steatoic liver. Together with several glycerophospholipids containing C22:6 fatty acid moiety they also classified early and advanced stages of NAFL.

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Authors: Tim Daniel Rose, Oskar Knittelfelder, Alessandra Palladini, Judith Andrea Heidrun Wodke, Kai Schuhmann, Jacobo Miranda Ackerman, Yuting Wang, Canan Has, Mario Brosch, Veera Raghavan Thangapandi, Stephan Buch, Christoph Roecken, Uenal Coscun, Edda Klipp, Witigo von Schönfels, Justus Gross, Clemens Schafmayer, Jochen Hampe, Olga Vvedenskaya, Josch Pauling, Andrej Schevchenko

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Created: 30th Jun 2021 at 16:12

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