Milk osteopontin mediates zinc uptake in intestinal cells in the presence of phytic acid

The bioavailability and the intestinal absorption of the essential mineral zinc are challenged by the food matrix and especially the content of zinc chelating antinutrients. Many milk proteins and peptides affect zinc bioavailability. Osteopontin (OPN) is an acidic and highly phosphorylated whey protein that has been shown to bind calcium, magnesium and iron. Here we report the zinc binding properties of OPN, and the effect of OPN-Zn complexes on zinc absorption in Caco-2 cells. By isothermal titration calorimetry milk OPN was shown to bind approximately 36 zinc ions (KD of ∼70 μM). The binding was mainly mediated by the phosphorylations in the protein. OPN retained zinc bound after in vitro simulated gastrointestinal transit. Interestingly the OPN-Zn complex enhanced zinc bioavailability in the presence of phytic acid, compared to inorganic zinc salts. Zinc uptake mediated by OPN significantly upregulated the gene expression of MT1G and ZnT1 which are crucial proteins involved in preserving enterocyte zinc homoeostasis. These results indicate that OPN could be incorporated into functional foods and infant formulas to increase zinc bioavailability and uptake.