Liver lipid metabolism is altered by increased circulating estrogen to androgen ratio in male mouse

Anni P Vehmas¹, Marion Adam², Teemu D Laajala³, Gabi Kastenmüller⁴, Cornelia Prehn⁵, Jan Rozman⁶, Claes Ohlsson⁷, Helmut Fuchs⁸, Martin Hrabě de Angelis⁹, Valérie Gailus-Durner⁸, Laura L Elo¹⁰, Tero Aittokallio¹¹, Jerzy Adamski¹², Garry Corthals¹³, Matti Poutanen¹⁴, Leena Strauss¹⁵

Affiliations

¹ Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, Turku, Finland; Department of Physiology, Institute of Biomedicine, University of Turku, Turku, Finland.
² Department of Physiology, Institute of Biomedicine, University of Turku, Turku, Finland; Turku Center for Disease Modeling, University of Turku, Turku, Finland.
³ 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.
⁴ Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, Neuherberg, Germany.
⁵ Genome Analysis Center, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
⁶ 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.
⁷ Centre for Bone and Arthritis Research, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.
⁸ German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
⁹ 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.
¹⁰ Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, Turku, Finland; Department of Mathematics and Statistics, University of Turku, Turku, Finland.
¹¹ Department of Mathematics and Statistics, University of Turku, Turku, Finland; Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Finland.
¹² 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.
¹³ 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.
¹⁴ 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.
¹⁵ 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.

PMID: 26691839
DOI: 10.1016/j.jprot.2015.12.009

Liver lipid metabolism is altered by increased circulating estrogen to androgen ratio in male mouse

Anni P Vehmas et al. J Proteomics. 2016.

. 2016 Feb 5:133:66-75.

doi: 10.1016/j.jprot.2015.12.009. Epub 2015 Dec 9.

Authors

Affiliations

¹ Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, Turku, Finland; Department of Physiology, Institute of Biomedicine, University of Turku, Turku, Finland.
² Department of Physiology, Institute of Biomedicine, University of Turku, Turku, Finland; Turku Center for Disease Modeling, University of Turku, Turku, Finland.
³ 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.
⁴ Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, Neuherberg, Germany.
⁵ Genome Analysis Center, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
⁶ 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.
⁷ Centre for Bone and Arthritis Research, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.
⁸ German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
⁹ 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.
¹⁰ Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, Turku, Finland; Department of Mathematics and Statistics, University of Turku, Turku, Finland.
¹¹ Department of Mathematics and Statistics, University of Turku, Turku, Finland; Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Finland.
¹² 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.
¹³ 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.
¹⁴ 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.
¹⁵ 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.

PMID: 26691839
DOI: 10.1016/j.jprot.2015.12.009

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.

Keywords: Aromatase; Label free quantitative proteomics; Liver; Male mouse; Metabolomics; Phospholipid.

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Liver lipid metabolism is altered by increased circulating estrogen to androgen ratio in male mouse

Affiliations

Liver lipid metabolism is altered by increased circulating estrogen to androgen ratio in male mouse

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Abstract

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