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Nutrients 2017, 9(7), 690; doi:10.3390/nu9070690

High Consumption of Iron Exacerbates Hyperlipidemia, Atherosclerosis, and Female Sterility in Zebrafish via Acceleration of Glycation and Degradation of Serum Lipoproteins

1,2,3,†
,
1,2,3,†
,
1,2,3,†
,
4,* and 1,2,3,*
1
Department of Medical Biotechnology, Yeungnam University, Gyeongsan 712-749, Korea
2
Research Institute of Protein Sensor, Yeungnam University, Gyeongsan 712-749, Korea
3
BK21plus Program Serum Biomedical Research and Education Team, Yeungnam University, Gyeongsan 712-749, Korea
4
Department of Biochemistry and Molecular Biology, College of Medicine, Yeungnam University, Daegu 705-717, Korea
These authors contributed equally to this work.
*
Authors to whom correspondence should be addressed.
Received: 5 June 2017 / Revised: 23 June 2017 / Accepted: 29 June 2017 / Published: 2 July 2017
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Abstract

Elevated serum iron level is linked with an increased risk of diabetes and atherosclerosis. However, the pathological mechanism by which iron affects serum lipoprotein levels is unknown. To elucidate the mechanism, a high dose of ferrous ion was applied (final 60 µM, 120 µM) to human serum lipoproteins, macrophages, and human dermal fibroblast (HDF) cells. Iron-treated lipoproteins showed loss of antioxidant ability along with protein degradation and multimerization, especially co-treatment with fructose (final 10 mM). In the presence of fructose, HDF cells showed 3.5-fold more severe cellular senescence, as compared to the control, dependent on the dosage of fructose. In macrophages, phagocytosis of acetylated low-density lipoprotein (acLDL) was more accelerated by ferrous ion, occurring at a rate that was up to 1.8-fold higher, than acLDL alone. After 24 weeks supplementation with 0.05% and 0.1% ferrous ion in the diet (wt/wt), serum total cholesterol (TC) level was elevated 3.7- and 2.1-fold, respectively, under normal diet (ND). Serum triglyceride (TG) was elevated 1.4- and 1.7-fold, respectively, under ND upon 0.05% and 0.1% ferrous ion supplementation. Serum glucose level was elevated 2.4- and 1.2-fold under ND and high cholesterol diet (HCD), respectively. However, body weight was decreased by the Fe2+ consumption. Iron consumption caused severe reduction of embryo laying and reproduction ability, especially in female zebrafish via impairment of follicular development. In conclusion, ferrous ion treatment caused more pro-atherogenic, and pro-senescence processes in human macrophages and dermal cells. High consumption of iron exacerbated hyperlipidemia and hyperglycemia as well as induced fatty liver changes and sterility along with reduction of female fertility. View Full-Text
Keywords: iron; lipoprotein; hyperlipidemia; cellular senescence; macrophages; human dermal fibroblast cells iron; lipoprotein; hyperlipidemia; cellular senescence; macrophages; human dermal fibroblast cells
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Kim, S.-H.; Yadav, D.; Kim, S.-J.; Kim, J.-R.; Cho, K. High Consumption of Iron Exacerbates Hyperlipidemia, Atherosclerosis, and Female Sterility in Zebrafish via Acceleration of Glycation and Degradation of Serum Lipoproteins. Nutrients 2017, 9, 690.

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