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Alteration in iron efflux affects male sex hormone testosterone biosynthesis in a diet-induced obese rat model

Author:
KurniawanThese authors contributed equally to this work., Adi Lukas, Lee, Yu-Chieh, Shih, Chun-Kuang, Hsieh, Rong-Hong, Chen, Seu-Hwa, Chang, Jung-Su
Source:
Food & function 2019 v.10 no.7 pp. 4113-4123
ISSN:
2042-650X
Subject:
Western blotting, adults, animal disease models, apoptosis, biogenesis, biosynthesis, diet, germ cells, hepcidin, iron, iron overload, laboratory animals, lipid content, males, men, mitochondria, obesity, proteins, rats, staining, testes, testosterone, therapeutics
Abstract:
This study was motivated by clinical observations that dysmetabolic iron overload syndrome (DIOS) and an androgen deficiency are common features observed in obese adult men; however, the molecular mechanism underlying the effects of DIOS on androgen deficiency remains to be elucidated. We established a DIOS animal model by feeding Sprague-Dawley rats an iron/fat-enriched diet (50% fat plus 0.25, 1, or 2 g ferric iron per kg diet) for 12 weeks to induce iron dysfunction (indicated by decreased tissue iron efflux) in obese rats. Obese rats fed an iron/fat-enriched diet showed decreased levels of testicular total Testosterone (T) and iron exporter ferroportin but increased levels of testicular iron and hepcidin, and these effects were more evident with a >1 g ferric iron per kg diet. A western blot analysis showed that an iron/fat-enriched diet triggered testicular endoplasmic reticular (ER) stress but decreased mitochondrion biogenesis proteins (PGC1α and TFAM) and T-converting proteins (StAR, CYP11A, and 17β-HSD). TUNEL staining showed that >1 g ferric iron induced apoptosis mainly in germ cells and Leydig's cells. Uncontrolled testicular iron efflux may cause mitochondrial-ER dysfunction and affect T biosynthesis. Future study targeting the testicular hepcidin–ferroportin axis may offer a therapeutic tool to alleviate testicular iron retention and mitochondrial-ER stress in Leydig's cells.
Agid:
6539499