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J Proteomics. 2016 Feb 5;133:66-75. doi: 10.1016/j.jprot.2015.12.009. Epub 2015 Dec 9.

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

Author information

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.

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

PMID:
26691839
DOI:
10.1016/j.jprot.2015.12.009
[Indexed for MEDLINE]

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