title: Malondialdehyde epitopes are sterile mediators of hepatic inflammation in hypercholesterolemic mice.
abstract: Diet-related health issues such as nonalcoholic fatty liver disease and cardiovascular disorders are known to have a major inflammatory component. However, the exact pathways linking diet-induced changes (e.g., hyperlipidemia) and the ensuing inflammation have remained elusive so far. We identified biological processes related to innate immunity and oxidative stress as prime response pathways in livers of low-density lipoprotein receptor-deficient mice on a Western-type diet using RNA sequencing and in silico functional analyses of transcriptome data. The observed changes were independent of the presence of microbiota and thus indicative of a role for sterile triggers. We further show that malondialdehyde (MDA) epitopes, products of lipid peroxidation and markers for enhanced oxidative stress, are detectable in hepatic inflammation predominantly on dying cells and stimulate cytokine secretion as well as leukocyte recruitment in vitro and in vivo. MDA-induced cytokine secretion in vitro was dependent on the presence of the scavenger receptors CD36 and MSR1. Moreover, in vivo neutralization of endogenously generated MDA epitopes by intravenous injection of a specific MDA antibody results in decreased hepatic inflammation in low-density lipoprotein receptor-deficient mice on a Western-type diet.
  
  
  
  Accumulation of MDA epitopes plays a major role during diet-induced hepatic inflammation and can be ameliorated by administration of an anti-MDA antibody. (Hepatology 2017;65:1181-1195).
authors.affiliation: Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria.|CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.
authors.forename: Clara Jana-Lui
authors.initials: CJ
authors.lastname: Busch
authors.affiliation: Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria.|CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.|Department of Molecular Genetics, School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, The Netherlands.
authors.forename: Tim
authors.initials: T
authors.lastname: Hendrikx
authors.affiliation: Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria.|CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.
authors.forename: David
authors.initials: D
authors.lastname: Weismann
authors.affiliation: Center for Thrombosis and Haemostasis, University Medical Center Mainz, Mainz, Germany.|German Center for Cardiovascular Research, Partner Site Rhein/Main, Mainz, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Jäckel
authors.affiliation: Department of Molecular Genetics, School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, The Netherlands.
authors.forename: Sofie M A
authors.initials: SM
authors.lastname: Walenbergh
authors.affiliation: CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.
authors.forename: André F
authors.initials: AF
authors.lastname: Rendeiro
authors.affiliation: CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.
authors.forename: Juliane
authors.initials: J
authors.lastname: Weißer
authors.affiliation: Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria.|CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.
authors.forename: Florian
authors.initials: F
authors.lastname: Puhm
authors.affiliation: CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.|Laboratory of Infection Biology, Department of Medicine 1, Medical University of Vienna, Vienna, Austria.
authors.forename: Anastasiya
authors.initials: A
authors.lastname: Hladik
authors.affiliation: Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria.|CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.
authors.forename: Laura
authors.initials: L
authors.lastname: Göderle
authors.affiliation: Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria.|CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.
authors.forename: Nikolina
authors.initials: N
authors.lastname: Papac-Milicevic
authors.affiliation: Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria.|CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.
authors.forename: Gerald
authors.initials: G
authors.lastname: Haas
authors.affiliation: Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria.|CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.
authors.forename: Vincent
authors.initials: V
authors.lastname: Millischer
authors.affiliation: Center for Thrombosis and Haemostasis, University Medical Center Mainz, Mainz, Germany.
authors.forename: Saravanan
authors.initials: S
authors.lastname: Subramaniam
authors.affiliation: CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.|Laboratory of Infection Biology, Department of Medicine 1, Medical University of Vienna, Vienna, Austria.
authors.forename: Sylvia
authors.initials: S
authors.lastname: Knapp
authors.affiliation: CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.
authors.forename: Keiryn L
authors.initials: KL
authors.lastname: Bennett
authors.affiliation: Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria.|CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.|Max Planck Institute for Informatics, Saarbrücken, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Bock
authors.affiliation: Center for Thrombosis and Haemostasis, University Medical Center Mainz, Mainz, Germany.|German Center for Cardiovascular Research, Partner Site Rhein/Main, Mainz, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Reinhardt
authors.affiliation: Department of Molecular Genetics, School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, The Netherlands.
authors.forename: Ronit
authors.initials: R
authors.lastname: Shiri-Sverdlov
authors.affiliation: Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria.|CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.
authors.forename: Christoph J
authors.initials: CJ
authors.lastname: Binder
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001707:Biopsy, Needle; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D066273:Diet, Western; D004195:Disease Models, Animal; D000939:Epitopes / Q000276:immunology / Q000378:metabolism*; D005234:Fatty Liver / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D006937:Hypercholesterolemia / Q000473:pathology* / Q000503:physiopathology; D007113:Immunity, Innate; D007150:Immunohistochemistry; D018836:Inflammation Mediators / Q000378:metabolism; D015227:Lipid Peroxidation; D008315:Malondialdehyde / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D064307:Microbiota; D018384:Oxidative Stress; D011897:Random Allocation
chemical_list: D016207:Cytokines; D000939:Epitopes; D018836:Inflammation Mediators; D008315:Malondialdehyde