Journal of Lipid Research (Jan 2021)
Nonalcoholic fatty liver disease stratification by liver lipidomics
- Olga Vvedenskaya,
- 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,
- 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
Affiliations
- Olga Vvedenskaya
- Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany
- Tim Daniel Rose
- LipiTUM, Chair of Experimental Bioinformatics, TUM School of Life Sciences, Technical University of Munich, Munich, Germany
- Oskar Knittelfelder
- Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany
- Alessandra Palladini
- Paul Langerhans Institute Dresden of the Helmholtz Zentrum Munich at the University Hospital Carl Gustav Carus, Technische Universität (TU) Dresden, Dresden, Germany; German Center for Diabetes Research (DZD e.V.), Neuherberg, Germany
- Judith Andrea Heidrun Wodke
- Theoretical Biophysics, Humboldt-Universität zu Berlin, Berlin, Germany
- Kai Schuhmann
- Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany
- Jacobo Miranda Ackerman
- Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany
- Yuting Wang
- Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany
- Canan Has
- Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany
- Mario Brosch
- Department of Medicine I, University Hospital Dresden, Technische Universität (TU) Dresden, Dresden, Germany; Center for Regenerative Therapies Dresden (CRTD), Technische Universität (TU) Dresden, Dresden, Germany
- Veera Raghavan Thangapandi
- Department of Medicine I, University Hospital Dresden, Technische Universität (TU) Dresden, Dresden, Germany; Center for Regenerative Therapies Dresden (CRTD), Technische Universität (TU) Dresden, Dresden, Germany
- Stephan Buch
- Department of Medicine I, University Hospital Dresden, Technische Universität (TU) Dresden, Dresden, Germany; Center for Regenerative Therapies Dresden (CRTD), Technische Universität (TU) Dresden, Dresden, Germany
- Thomas Züllig
- Core Facility Mass Spectrometry, Medical University of Graz, Graz, Austria
- Jürgen Hartler
- Institute of Pharmaceutical Sciences, University of Graz, Graz, Austria; Field of Excellence BioHealth, University of Graz, Graz, Austria
- Harald C. Köfeler
- Core Facility Mass Spectrometry, Medical University of Graz, Graz, Austria
- Christoph Röcken
- Department of Pathology, University Hospital Schleswig Holstein, Kiel, Schleswig-Holstein, Germany
- Ünal Coskun
- Paul Langerhans Institute Dresden of the Helmholtz Zentrum Munich at the University Hospital Carl Gustav Carus, Technische Universität (TU) Dresden, Dresden, Germany; German Center for Diabetes Research (DZD e.V.), Neuherberg, Germany; Department of Membrane Biochemistry and Lipid Research, University Hospital Carl Gustav Carus of Technische Universität Dresden, Dresden, Germany
- Edda Klipp
- Theoretical Biophysics, Humboldt-Universität zu Berlin, Berlin, Germany
- Witigo von Schoenfels
- Department of Visceral and Thoracic Surgery, University Hospital Schleswig-Holstein, Kiel Campus, Christian-Albrechts-University Kiel, Kiel, Germany; Christian Albrechts University in Kiel Center of Clinical Anatomy Kiel, Schleswig-Holstein, Germany
- Justus Gross
- Department of General, Visceral, Vascular and Transplant Surgery, Rostock University Medical Center, Rostock, Germany
- Clemens Schafmayer
- Department of General, Visceral, Vascular and Transplant Surgery, Rostock University Medical Center, Rostock, Germany
- Jochen Hampe
- Department of Medicine I, University Hospital Dresden, Technische Universität (TU) Dresden, Dresden, Germany
- Josch Konstantin Pauling
- LipiTUM, Chair of Experimental Bioinformatics, TUM School of Life Sciences, Technical University of Munich, Munich, Germany; For correspondence: Josch Konstantin Pauling; Andrej Shevchenko
- Andrej Shevchenko
- Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany; For correspondence: Josch Konstantin Pauling; Andrej Shevchenko
- Journal volume & issue
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Vol. 62
p. 100104
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.
