title: Lipidomic analysis of lipid droplets from murine hepatocytes reveals distinct signatures for nutritional stress.
abstract: Liver steatosis can be induced by fasting or high-fat diet. We investigated by lipidomic analysis whether such metabolic states are reflected in the lipidome of hepatocyte lipid droplets (LDs) from mice fed normal chow diet (FED), fasted (FAS), or fed a high-fat diet (HFD). LC-MS/MS at levels of lipid species profiles and of lipid molecular species uncovered a FAS phenotype of LD enriched in triacylglycerol (TG) molecular species with very long-chain (VLC)-PUFA residues and an HFD phenotype with less unsaturated TG species in addition to characteristic lipid marker species. Nutritional stress did not result in dramatic structural alterations in diacylglycerol (DG) and phospholipid (PL) classes. Moreover, molecular species of bulk TG and of DG indicated concomitant de novo TG synthesis and lipase-catalyzed degradation to be active in LDs. DG species with VLC-PUFA residues would be preferred precursors for phosphatidylcholine (PC) species, the others for TG molecular species. In addition, molecular species of PL classes fitted the hepatocyte Kennedy and phosphatidylethanolamine methyltransferase pathways. We demonstrate that lipidomic analysis of LDs enables phenotyping of nutritional stress. TG species are best suited for such phenotyping, whereas structural analysis of TG, DG, and PL molecular species provides metabolic insights.
authors.affiliation: Department of Molecular Biosciences, University of Graz, Lipidomics Research Center, 8010 Graz, Austria.
authors.forename: Chandramohan
authors.initials: C
authors.lastname: Chitraju
authors.affiliation: Core Facility for Mass Spectrometry, Center for Medical Research, Medical University of Graz, Lipidomics Research Center, 8010 Graz, Austria.
authors.forename: Martin
authors.initials: M
authors.lastname: Trötzmüller
authors.affiliation: Institute for Genomics and Bioinformatics, Graz University of Technology, and Core Facility Bioinformatics, Austrian Centre for Industrial Biotechnology, 8010 Graz, Austria.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Hartler
authors.affiliation: Department of Molecular Biosciences, University of Graz, Lipidomics Research Center, 8010 Graz, Austria.
authors.forename: Heimo
authors.initials: H
authors.lastname: Wolinski
authors.affiliation: Institute for Genomics and Bioinformatics, Graz University of Technology, and Core Facility Bioinformatics, Austrian Centre for Industrial Biotechnology, 8010 Graz, Austria.
authors.forename: Gerhard G
authors.initials: GG
authors.lastname: Thallinger
authors.affiliation: Department of Molecular Biosciences, University of Graz, Lipidomics Research Center, 8010 Graz, Austria.
authors.forename: Achim
authors.initials: A
authors.lastname: Lass
authors.affiliation: Department of Molecular Biosciences, University of Graz, Lipidomics Research Center, 8010 Graz, Austria.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Zechner
authors.affiliation: Department of Molecular Biosciences, University of Graz, Lipidomics Research Center, 8010 Graz, Austria.
authors.forename: Robert
authors.initials: R
authors.lastname: Zimmermann
authors.affiliation: Core Facility for Mass Spectrometry, Center for Medical Research, Medical University of Graz, Lipidomics Research Center, 8010 Graz, Austria.
authors.forename: Harald C
authors.initials: HC
authors.lastname: Köfeler
authors.affiliation: Department of Molecular Biosciences, University of Graz, Lipidomics Research Center, 8010 Graz, Austria. Electronic address: fritz.spener@uni-graz.at.
authors.forename: Friedrich
authors.initials: F
authors.lastname: Spener
mesh_terms: D000818:Animals; D059305:Diet, High-Fat; D004075:Diglycerides / Q000378:metabolism; D005215:Fasting; D022781:Hepatocytes / Q000737:chemistry / Q000378:metabolism*; D008049:Lipase / Q000378:metabolism; D008055:Lipids / Q000032:analysis*; D008099:Liver / Q000737:chemistry / Q000378:metabolism*; D051379:Mice; D010713:Phosphatidylcholines / Q000378:metabolism; D050918:Phosphatidylethanolamine N-Methyltransferase / Q000378:metabolism; D013312:Stress, Physiological; D014280:Triglycerides / Q000378:metabolism
chemical_list: C011439:1,2-diacylglycerol; D004075:Diglycerides; D008055:Lipids; D010713:Phosphatidylcholines; D014280:Triglycerides; D050918:Phosphatidylethanolamine N-Methyltransferase; D008049:Lipase