title: Liver lipid metabolism is altered by increased circulating estrogen to androgen ratio in male mouse.
abstract: Estrogens are suggested to lower the risk of developing metabolic syndrome in both sexes. In this study, we investigated how the increased circulating estrogen-to-androgen ratio (E/A) alters liver lipid metabolism in males. The cytochrome P450 aromatase (P450arom) is an enzyme converting androgens to estrogens. Male mice overexpressing human aromatase enzyme (AROM+ mice), and thus have high circulating E/A, were used as a model in this study. Proteomics and gene expression analyses indicated an increase in the peroxisomal β-oxidation in the liver of AROM+ mice as compared with their wild type littermates. Correspondingly, metabolomic analysis revealed a decrease in the amount of phosphatidylcholines with long-chain fatty acids in the plasma. With interest we noted that the expression of Cyp4a12a enzyme, which specifically metabolizes arachidonic acid (AA) to 20-hydroxy AA, was dramatically decreased in the AROM+ liver. As a consequence, increased amounts of phospholipids having AA as a fatty acid tail were detected in the plasma of the AROM+ mice. Overall, these observations demonstrate that high circulating E/A in males is linked to indicators of higher peroxisomal β-oxidation and lower AA metabolism in the liver. Furthermore, the plasma phospholipid profile reflects the changes in the liver lipid metabolism.
authors.affiliation: Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, Turku, Finland; Department of Physiology, Institute of Biomedicine, University of Turku, Turku, Finland.
authors.forename: Anni P
authors.initials: AP
authors.lastname: Vehmas
authors.affiliation: Department of Physiology, Institute of Biomedicine, University of Turku, Turku, Finland; Turku Center for Disease Modeling, University of Turku, Turku, Finland.
authors.forename: Marion
authors.initials: M
authors.lastname: Adam
authors.affiliation: Turku Center for Disease Modeling, University of Turku, Turku, Finland; Department of Mathematics and Statistics, University of Turku, Turku, Finland; Drug Research Doctoral Programme, University of Turku, Finland; Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Finland.
authors.forename: Teemu D
authors.initials: TD
authors.lastname: Laajala
authors.affiliation: Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, Neuherberg, Germany.
authors.forename: Gabi
authors.initials: G
authors.lastname: Kastenmüller
authors.affiliation: Genome Analysis Center, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Prehn
authors.affiliation: German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany; German Center for Diabetes Research (DZD), Neuherberg, Germany; Molecular Nutritional Medicine, Else Kröner-Fresenius Center, Technische Universität München, Freising-Weihenstephan, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Rozman
authors.affiliation: Centre for Bone and Arthritis Research, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Claes
authors.initials: C
authors.lastname: Ohlsson
authors.affiliation: German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
authors.forename: Helmut
authors.initials: H
authors.lastname: Fuchs
authors.affiliation: German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany; German Center for Diabetes Research (DZD), Neuherberg, Germany; Experimental Genetics, Center of Life and Food Sciences Weihenstephan, Technische Universität München, Neuherberg, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Hrabě de Angelis
authors.affiliation: German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
authors.forename: Valérie
authors.initials: V
authors.lastname: Gailus-Durner
authors.affiliation: Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, Turku, Finland; Department of Mathematics and Statistics, University of Turku, Turku, Finland.
authors.forename: Laura L
authors.initials: LL
authors.lastname: Elo
authors.affiliation: Department of Mathematics and Statistics, University of Turku, Turku, Finland; Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Finland.
authors.forename: Tero
authors.initials: T
authors.lastname: Aittokallio
authors.affiliation: Genome Analysis Center, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany; German Center for Diabetes Research (DZD), Neuherberg, Germany; Experimental Genetics, Center of Life and Food Sciences Weihenstephan, Technische Universität München, Neuherberg, Germany.
authors.forename: Jerzy
authors.initials: J
authors.lastname: Adamski
authors.affiliation: Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, Turku, Finland; Van 't Hoff Institute for Molecular Sciences, University of Amsterdam, The Netherlands.
authors.forename: Garry
authors.initials: G
authors.lastname: Corthals
authors.affiliation: Department of Physiology, Institute of Biomedicine, University of Turku, Turku, Finland; Turku Center for Disease Modeling, University of Turku, Turku, Finland; Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Sweden.
authors.forename: Matti
authors.initials: M
authors.lastname: Poutanen
authors.affiliation: Department of Physiology, Institute of Biomedicine, University of Turku, Turku, Finland; Turku Center for Disease Modeling, University of Turku, Turku, Finland. Electronic address: leesal@utu.fi.
authors.forename: Leena
authors.initials: L
authors.lastname: Strauss
mesh_terms: D000728:Androgens / Q000097:blood* / Q000235:genetics; D000818:Animals; D001141:Aromatase / Q000235:genetics / Q000378:metabolism*; D004967:Estrogens / Q000097:blood* / Q000235:genetics; D006801:Humans; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D020675:Peroxisomes / Q000235:genetics / Q000378:metabolism*; D010713:Phosphatidylcholines / Q000096:biosynthesis / Q000235:genetics
chemical_list: D000728:Androgens; D004967:Estrogens; D010713:Phosphatidylcholines; D001141:Aromatase
keywords: Aromatase; Label free quantitative proteomics; Liver; Male mouse; Metabolomics; Phospholipid