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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Cell Dev. Biol. | doi: 10.3389/fcell.2019.00248

Fatty liver due to increased de novo lipogenesis: alterations in the hepatic peroxisomal proteome

 Birgit Knebel1*, Pia Fahlbusch1, Matthias Dille1, Natalie Wahlers1, Sonja Hartwig1, Sylvia Jacob1, Ulrike Kettel1, Martina Schiller1, Diran Herebian2, Cornelia Koellmer1, Stefan Lehr3, Dirk Mülle-Wieland4 and joerg kotzka1
  • 1Institute for Clinical Biochemistry and Pathobiochemistry, German Diabetes Center, Heinrich Heine University of Dusseldorf, Germany
  • 2Department of General Pediatrics, Neonatology and Pediatric Cardiology, University Hospital of Düsseldorf, Germany
  • 3Institute for Clinical Diabetology, German Diabetes Center, Heinrich Heine University of Dusseldorf, Germany
  • 4Department of Cardiology, Pulmonology, Angiology and Intensive Care Medicine, University Hospital RWTH Aachen, Germany

In non-alcoholic fatty liver disease (NAFLD) caused by ectopic lipid accumulation, lipotoxicity is a crucial molecular risk factor. Mechanisms to eliminate lipid overflow can prevent the liver from functional complications. This may involve increased secretion of lipids or metabolic adaptation to ß-oxidation in lipid-degrading organelles such as mitochondria and peroxisomes. In addition to dietary factors, increased plasma fatty acid levels may be due to increased triglyceride synthesis, lipolysis, as well as de novo lipid synthesis (DNL) in the liver. In the present study, we investigated the impact of fatty liver caused by elevated de novo lipid synthesis, in a transgenic mouse model with liver-specific overexpression of human sterol regulatory element-binding protein-1c (alb-SREBP-1c), on hepatic gene expression, on plasma lipids and especially on the proteome of peroxisomes by omics analyses, and we interpreted the results with knowledge-based analyses. In summary, the increased hepatic DNL is accompanied by marginal gene expression changes but massive changes in peroxisomal proteome. Furthermore, plasma phosphatidylcholine (PC) as well as lysoPC species were altered. Based on these observations, it can be speculated that the plasticity of organelles and their functionality may be directly affected by lipid overflow.

Keywords: NAFLD, Fatty Liver, Peroxisomes, label-free proteomic profiling, Transcriptomics, lipidomics, SREBP-1c, DNL

Received: 12 Aug 2019; Accepted: 08 Oct 2019.

Copyright: © 2019 Knebel, Fahlbusch, Dille, Wahlers, Hartwig, Jacob, Kettel, Schiller, Herebian, Koellmer, Lehr, Mülle-Wieland and kotzka. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Birgit Knebel, Institute for Clinical Biochemistry and Pathobiochemistry, German Diabetes Center, Heinrich Heine University of Dusseldorf, Duesseldorf, Germany, birgit.knebel@ddz.de