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Iron and Advanced Glycation End Products: Emerging Role of Iron in Androgen Deficiency in Obesity

Authors
  • Chen, Seu-Hwa
  • Yuan, Kuo-Ching
  • Lee, Yu-Chieh
  • Shih, Chun-Kuang
  • Tseng, Sung-Hui1
  • Tinkov, Alexey A.2, 3, 4
  • Skalny, Anatoly V.2, 3, 4
  • Chang, Jung-Su5, 6, 7
  • 1 Department of Physical Medicine and Rehabilitation, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan
  • 2 (A.V.S.)
  • 3 Laboratory of Biotechnology and Applied Bioelementology, Yaroslavl State University, Yaroslavl 150003, Russia
  • 4 Laboratory of Molecular Dietology, IM Sechenov First Moscow State Medical University, Moscow 119146, Russia
  • 5 Graduate Institute of Metabolism and Obesity Sciences, College of Nutrition, Taipei Medical University, Taipei 110, Taiwan
  • 6 Nutrition Research Center, Taipei Medical University Hospital, Taipei 110, Taiwan
  • 7 Chinese Taipei Society for the Study of Obesity (CTSSO), Taipei 110, Taiwan
Type
Published Article
Journal
Antioxidants
Publisher
MDPI AG
Publication Date
Mar 22, 2020
Volume
9
Issue
3
Identifiers
DOI: 10.3390/antiox9030261
PMID: 32235809
PMCID: PMC7139764
Source
PubMed Central
Keywords
License
Green

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( ɛ )-(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.

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