Copper supplementation reverses dietary iron overload-induced pathologies in mice

Tao Wang, Ping Xiang, Jung Heun Ha, Xiaoyu Wang, Caglar Doguer, Shireen R.L. Flores, Yujian Kang, James F. Collins

Research output: Contribution to journalArticle

Abstract

Dietary iron overload in rodents impairs growth and causes cardiac hypertrophy, serum and tissue copper depletion, depression of serum ceruloplasmin (Cp) activity and anemia. Notably, increasing dietary copper content to ~25-fold above requirements prevents the development of these physiological perturbations. Whether copper supplementation can reverse these high-iron-related abnormalities has, however, not been established. The current investigation was thus undertaken to test the hypothesis that supplemental copper will mitigate negative outcomes associated with dietary iron loading. Weanling mice were thus fed AIN-93G-based diets with high (>100-fold in excess) or adequate (~80 ppm) iron content. To establish the optimal experimental conditions, we first defined the time course of iron loading, and assessed the impact of supplemental copper (provided in drinking water) on the development of high-iron-related pathologies. Copper supplementation (20 mg/L) for the last 3 weeks of a 7-week high-iron feeding period reversed the anemia, normalized serum copper levels and Cp activity, and restored tissue copper concentrations. Growth rates, cardiac copper concentrations and heart size, however, were only partially normalized by copper supplementation. Furthermore, high dietary iron intake reduced intestinal 64 Cu absorption (~60%) from a transport solution provided to mice by oral, intragastric gavage. Copper supplementation of iron-loaded mice enhanced intestinal 64 Cu transport, thus allowing sufficient assimilation of dietary copper to correct many of the noted high-iron-related physiological perturbations. We therefore conclude that high- iron intake increases the requirement for dietary copper (to overcome the inhibition of intestinal copper absorption).

Original languageEnglish (US)
Pages (from-to)56-63
Number of pages8
JournalJournal of Nutritional Biochemistry
Volume59
DOIs
StatePublished - Sep 1 2018

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Dietary Iron
Iron Overload
Pathology
Copper
Iron
Ceruloplasmin
Anemia
Serum
Tissue
Nutritional Requirements
Intestinal Absorption
Cardiomegaly
Nutrition
Growth

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Biology
  • Nutrition and Dietetics
  • Clinical Biochemistry

Cite this

Wang, T., Xiang, P., Ha, J. H., Wang, X., Doguer, C., Flores, S. R. L., ... Collins, J. F. (2018). Copper supplementation reverses dietary iron overload-induced pathologies in mice. Journal of Nutritional Biochemistry, 59, 56-63. https://doi.org/10.1016/j.jnutbio.2018.05.006

Copper supplementation reverses dietary iron overload-induced pathologies in mice. / Wang, Tao; Xiang, Ping; Ha, Jung Heun; Wang, Xiaoyu; Doguer, Caglar; Flores, Shireen R.L.; Kang, Yujian; Collins, James F.

In: Journal of Nutritional Biochemistry, Vol. 59, 01.09.2018, p. 56-63.

Research output: Contribution to journalArticle

Wang, Tao ; Xiang, Ping ; Ha, Jung Heun ; Wang, Xiaoyu ; Doguer, Caglar ; Flores, Shireen R.L. ; Kang, Yujian ; Collins, James F. / Copper supplementation reverses dietary iron overload-induced pathologies in mice. In: Journal of Nutritional Biochemistry. 2018 ; Vol. 59. pp. 56-63.
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