Strategies for Inducing and Validating Zinc Deficiency and Zinc Repletion

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Background: According to the World Health Organization, zinc deficiency is a growing global health problem, impacting 31% of the world’s population. Zinc deficiency is a common comorbidity with many chronic diseases, from skin to kidney diseases. Given the increasing interest in zinc’s role in disease onset and progression, there is a dire need for reproducible approaches to manipulate zinc homeostasis. Here, we provide proven strategies for inducing and validating zinc deficiency and zinc repletion in a mouse model. Experimental Design: After acclimating to a ZnA (zinc adequate) diet, mice are randomly assigned to either a ZnA or ZnD (zinc deficient) diet. To replete zinc levels (ZnR), a subset of ZnD mice is returned to the ZnA diet. Animal growth rates and plasma zinc levels are assessed to validate zinc status. Results: Mice placed on the ZnD-diet have reduced body weights (26.48g ± 0.78) compared to mice maintained on the ZnA-diet (28.12g ± 0.13). However, zinc repletion promotes weight gain (27.87g ± 1.01) resulting in body weights comparable to mice maintained on the ZnA-diet. Furthermore, mice maintained on the ZnA-diet have plasma zinc levels of 3.19 μM/g Body Weight. While plasma zinc levels are 40% lower in mice place on the ZnD-diet (1.29 μM/g Body Weight). In contrast, plasma zinc levels (2.44 μM/g Body Weight) are increased in ZnR mice. Conclusion: These findings validate that the described dietary approach is an effective strategy for inducing zinc deficiency and zinc repletion. Significance: This cost-effcient approach will enhance the scientific rigor and reproducibility of studies examining the impact of zinc deficiency, and repletion on disease onset and progression. Funding Source: R21 DK119879, R01 DK-133698. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.