Weight gain and inflammation regulate aromatase expression in male adipose tissue, as evidenced by reporter gene activity

L Polari, E Yatkin, Gabriela Martinez Chacon, M Ahotupa, A Smeds, L Strauss, F Zhang, M Poutanen, N Saarinen, S I Mäkelä

Research output: Contribution to journalArticleScientificpeer-review

Abstract

Obesity and white adipose tissue (WAT) inflammation are associated with enhanced aromatization in women, but little is known about the regulation of aromatase (CYP19A1) gene expression in male WAT. We investigated the impact of weight gain and WAT inflammation on the regulation of CYP19A1 in males, by utilizing the hARO-Luc aromatase reporter mouse model containing a >100-kb 5'-region of the human CYP19A1 gene. We show that hARO-Luc reporter activity is enhanced in WAT of mice with increased adiposity and inflammation. Dexamethasone and TNFα, as well as forskolin and phorbol 12-myristate 13-acetate, upregulate hARO-Luc activity, suggesting the involvement of promoters I.4 and I.3/II. Furthermore, we show that diet enriched with antioxidative plant polyphenols attenuates WAT inflammation and hARO-Luc activity in obese males. In conclusion, our data suggest that obesity-associated WAT inflammation leads to increased peripheral CYP19A1 expression in males, and that polyphenol-enriched diet may have the potential to attenuate excessive aromatization in WAT of obese men.

Original languageEnglish
Pages (from-to)123-30
Number of pages8
JournalMolecular and Cellular Endocrinology
Volume412
DOIs
Publication statusPublished - 5 Sep 2015
MoE publication typeA1 Journal article-refereed

Keywords

  • Adipose Tissue, White/enzymology
  • Animals
  • Antioxidants/administration & dosage
  • Aromatase/genetics
  • Cells, Cultured
  • Cytokines/blood
  • Diet, High-Fat/adverse effects
  • Enzyme Induction
  • Gene Expression
  • Genes, Reporter
  • Luciferases/biosynthesis
  • Male
  • Mice
  • Obesity/etiology
  • Plant Extracts/administration & dosage
  • Polyphenols/administration & dosage
  • Transcriptional Activation
  • Weight Gain

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