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.
Antioxidants (Basel, Switzerland). 2020 Mar 22*** epublish ***
Seu-Hwa Chen, Kuo-Ching Yuan, Yu-Chieh Lee, Chun-Kuang Shih, Sung-Hui Tseng, Alexey A Tinkov, Anatoly V Skalny, Jung-Su Chang
Department of Anatomy and Cell Biology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan., Department of Emergency and Critical Care Medicine, Taipei Medical University Hospital, Taipei 110, Taiwan., Department of Obstetrics and Gynecology, Taipei Medical University Hospital, Taipei 110, Taiwan., School of Nutrition and Health Sciences, College of Nutrition, Taipei Medical University, Taipei 110, Taiwan., Department of Physical Medicine and Rehabilitation, Taipei Medical University Hospital, Taipei 110, Taiwan., Department of Medical Elementology, Peoples' Friendship University of Russia (RUDN University), Moscow 117198, Russia.