Poster Topical Area: Medical Nutrition

Location: Hall D

Poster Board Number: 654

P14-030 - Copper supplementation in drinking water reverses dietary iron overload-induced anemia and cardiac hypertrophy in mice

Monday, Jun 11
8:00 AM – 3:00 PM

Objectives: Our previous studies showed that high-iron (0.88% carbonyl iron) diet feeding of mice and rats lead to impaired growth, severe anemia, tissue copper depletion and cardiac hypertrophy.1,2 Interestingly, these physiological perturbations were prevented by adding extra copper to the high Fe diet, proving that they were the consequence of severe copper deficiency. Whether these pathophysiological changes could be reversed by copper treatment, however, is unknown. The current study was thus undertaken to test the hypothesis that Cu supplementation of dietary Fe overload mice could restore systemic copper status, and reverse the anemia and cardiac hypertrophy.
Methods and
Results:
Weanling, male C57BL/6 mice were fed AIN-93G-based diets containing adequate (~8 ppm) Cu in combination with adequate (~80 ppm) or high (~8000 ppm) Fe for 4 weeks. Then, the mice were given 20 mg/L Cu (as Cu sulfate) in drinking water for another 3 weeks. Subsequently, the iron and copper-related phenotype of the mice was assessed. High-Fe diet fed mice showed a significant growth impairment and systemic Cu deficiency, accompanied by severe anemia, decreased serum ceruloplamine (Cp) activity and cardiac hypertrophy. Cu replenishment via drinking water corrected the deficits in hemoglobin (Hb), hematocrit (HCT) and serum Cp levels, restored tissue Cu status, and reversed cardiac hypertrophy. It was further found that high-Fe feeding significantly impaired intestinal Cu absorption, and disturbed Cu tissue distribution.

Conclusion:
This study demonstrates that high Fe consumption blocks intestinal Cu absorption, leading to a systemic Cu deficiency which resulted in a severe anemia and cardiac hypertrophy in mice. Cu supplementation corrects these physiologic perturbations associated with high Fe consumption. These observations have important implications for investigators that utilize the dietary iron overload model in that high-iron feeding should likely be accompanied by copper supplementation to prevent these noted physiologic perturbations that are not directly related to tissue iron accumulation. Moreover, this study has provided further evidence of physiologically-relevant iron-copper interactions in mammals.



Funding Source: Supported byNIH grant 1R01 DK074867 (to J.F.C.).
Figure 1. Consumption of a HFe diet by weanling, male mice causes notable pathological outcomes in only 2 weeks.

Figure 2. High-iron diet feeding induces severe systemic copper deficiency, decreases serum Cp activity, and eventually caused cardiac hypertrophy after 4 weeks.

Figure 3. Copper supplementation reverses the anemia associated with dietary iron loading in weanling, male mice.

Figure 4. Copper supplementation reestablished copper homeostasis in weanling, male mice with dietary iron overload.

Figure 5. Copper supplementation restores heart copper concentrations and reveres cardiac hypertrophy in dietary iron overload weanling, male mice.

CoAuthors: Ping Xiang – Nanjing University; Jung-Heun Ha – University of Florida; Caglar Doguer – University of Florida; Xiaoyu Wang – University of Florida; Shireen Flores – University of Florida; Y. James Kang – Sichuan University; James Collins – University of Florida

Tao Wang


Sichuan University
Chengdu, Sichuan, China (People's Republic)