Metallomic profiling of mouse tissues under differential dietary zinc intake

Zinc is an essential trace element, yet how graded dietary zinc intake reshapes tissue-specific distributions of zinc and other essential metals remains incompletely understood. This study investigated the impact of dietary zinc ranging from deficiency to high supplementation on the metallomic profile of C57BL/6 J mice. Mice were fed one of five zinc diets for 3 or 6 weeks, after which zinc status and related elements (copper, iron, manganese, calcium, and magnesium) were quantified in serum and multiple tissues by inductively coupled plasma-optical emission spectrometry, alongside expression of zinc transporter and metal-related genes in intestinal segments. Tissue zinc responses differed strongly across organs. Serum zinc increased only after prolonged supplementation, the colon and small intestine showed rapid and pronounced shifts with both deficiency and excess, brain and skeletal muscle regions displayed selective sensitivity, and liver and kidney zinc remained comparatively stable, consistent with strong homeostatic control. Dietary zinc did not deplete tissue copper but instead showed positive associations between zinc and copper in several tissues. We also observed co-ordinated and tissue-dependent relationships between zinc and iron, manganese, calcium, and magnesium, which challenges the traditional view that mineral interactions are uniformly antagonistic. When we integrated elemental and gene expression data and explicitly linked metal responses to measured tissue zinc levels, we identified segment-specific and transporter-specific adaptations that support a model in which dietary zinc reorganizes local and systemic mineral balance. This reorganization reflects both changes in tissue zinc levels and additional regulatory mechanisms in metal transport and storage that are not apparent from whole-tissue zinc measurements alone.