title: The impact of genetic stress by ATGL deficiency on the lipidome of lipid droplets from murine hepatocytes.
abstract: We showed earlier that nutritional stress like starvation or high-fat diet resulted in phenotypic changes in the lipidomes of hepatocyte lipid droplets (LDs), representative for the pathophysiological status of the mouse model. Here we extend our former study by adding genetic stress due to knockout (KO) of adipocyte triglyceride lipase (ATGL), the rate limiting enzyme in LD lipolysis. An intervention trial for 6 weeks with male wild-type (WT) and ATGL-KO mice was carried out; both genotypes were fed lab chow or were exposed to short-time starvation. Isolated LDs were analyzed by LC-MS/MS. Triacylglycerol, diacylglycerol, and phosphatidylcholine lipidomes, in that order, provided the best phenotypic signatures characteristic for respective stresses applied to the animals. This was evidenced at lipid species level by principal component analysis, calculation of average values for chain-lengths and numbers of double bonds, and by visualization in heat maps. Structural backgrounds for analyses and metabolic relationships were elaborated at lipid molecular species level. Relating our lipidomic data to nonalcoholic fatty liver diseases of nutritional and genetic etiologies with or without accompanying insulin resistance, phenotypic distinction in hepatocyte LDs dependent on insulin status emerged. Taken together, lipidomes of hepatocyte LDs are sensitive responders to nutritional and genetic stress.
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; and.
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: Guenter
authors.initials: G
authors.lastname: Haemmerle
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; and.
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; D004249:DNA Damage; D017353:Gene Deletion; D022781:Hepatocytes / Q000737:chemistry / Q000378:metabolism*; D008049:Lipase / Q000172:deficiency* / Q000235:genetics; D050356:Lipid Metabolism; D008055:Lipids; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010316:Particle Size; D000217:Acyltransferases
chemical_list: D008049:Lipase; D008055:Lipids; C494445:PNPLA2 protein, mouse; D000217:Acyltransferases
keywords: Lipid Data Analyzer; adipocyte triglyceride lipase; fasting; lipid species; mass spectrometry; nutritional stress; principal component analysis; steatosis; super stress