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

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


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Androgens / blood*
  • Androgens / genetics
  • Animals
  • Aromatase / genetics
  • Aromatase / metabolism*
  • Estrogens / blood*
  • Estrogens / genetics
  • Humans
  • Lipid Metabolism*
  • Liver / metabolism*
  • Male
  • Mice
  • Mice, Transgenic
  • Peroxisomes / genetics
  • Peroxisomes / metabolism*
  • Phosphatidylcholines / biosynthesis
  • Phosphatidylcholines / genetics


  • Androgens
  • Estrogens
  • Phosphatidylcholines
  • Aromatase