Iron and advanced glycation end products: Emerging role of iron in androgen deficiency in obesity

Seu Hwa Chen, Kuo Ching Yuan, Yu Chieh Lee, Chun Kuang Shih, Sung Hui Tseng, Alexey A. Tinkov, Anatoly V. Skalny, Jung Su Chang

Research output: Contribution to journalArticle

Abstract

The literature suggests a bidirectional relationship between testosterone (T) and iron, but mechanisms underlying this relationship remain unclear. We investigated effects of iron on advanced glycation end products (AGEs) in obesity-related androgen deficiency. In total, 111 men were recruited, and iron biomarkers and N(E)-(carboxymethyl)lysine (CML) were measured. In an animal study, rats were fed a 50% high-fat diet (HFD) with (0.25, 1, and 2 g ferric iron/kg diet) or without ferric citrate for 12 weeks. Obese rats supplemented with >1 g iron/kg diet had decreased testicular total T compared to HFD alone. Immunohistochemical staining showed that >1 g of ferric iron increased iron and AGE retention in testicular interstitial tissues, which is associated with increased expression of the receptor for AGEs (RAGE), tumor necrosis factor-α, and nitric oxide. Compared with normal weight, overweight/obese men had lower T levels and higher rates of hypogonadism (19% vs. 11.3%) and iron overload (29.8% vs.15.9%). A correlation analysis showed serum total T was positively correlated with transferrin saturation (r = 0.242, p = 0.007) and cathepsin D (r = 0.330, p = 0.001), but negatively correlated with red blood cell aggregation (r = −0.419, p<0.0001) and CML (r = −0.209, p < 0.05). In conclusion, AGEs may partially explain the underlying relationship between dysregulated iron and T deficiency.

Original languageEnglish
Article number261
JournalAntioxidants
Volume9
Issue number3
DOIs
Publication statusPublished - Mar 2020

Keywords

  • Advanced glycation end products
  • Fat
  • Iron
  • Obesity
  • Testis
  • Testosterone

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

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