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Nonalcoholic fatty liver disease stratification by liver lipidomics.

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Vvedenskaya,  Olga
Max Planck Institute for Molecular Cell Biology and Genetics, Max Planck Society;

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Knittelfelder,  Oskar
Max Planck Institute for Molecular Cell Biology and Genetics, Max Planck Society;

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Schuhmann,  Kai
Max Planck Institute for Molecular Cell Biology and Genetics, Max Planck Society;

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Wang,  Yuting
Max Planck Institute for Molecular Cell Biology and Genetics, Max Planck Society;

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Has,  Canan
Max Planck Institute for Molecular Cell Biology and Genetics, Max Planck Society;

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Shevchenko,  Andrej
Max Planck Institute for Molecular Cell Biology and Genetics, Max Planck Society;

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Citation

Vvedenskaya, O., Rose, T. D., Knittelfelder, O., Palladini, A., Wodke, J. A., Schuhmann, K., et al. (2021). Nonalcoholic fatty liver disease stratification by liver lipidomics. Journal of lipid research, 62: 100104. doi:10.1016/j.jlr.2021.100104.


Cite as: https://hdl.handle.net/21.11116/0000-000A-0BA1-4
Abstract
Nonalcoholic 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 nonsteatotic patients with normal or excessive weight, patients diagnosed with NAFL (nonalcoholic fatty liver) or NASH (nonalcoholic steatohepatitis), and patients bearing common mutations of NAFLD-related protein factors. We confirmed the progressive accumulation of di- and triacylglycerols 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 nonsteatotic livers. Together with several glycerophospholipids containing a C22:6 fatty acid moiety, these lipids serve as markers of early and advanced stages of NAFL.