Poster Topical Area: Medical Nutrition
Location: Hall D
Poster Board Number: 654
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.
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.
Chengdu, Sichuan, China (People's Republic)