Dietary metal chelator, phytochelatin 2, increases selenium and alters metal homeostasis and associated lipid metabolism in the liver

Biological systems have evolved highly regulated systems to ensure homeostatic levels of trace minerals, such as selenium (Se), which are important to metabolic function and signaling. Much of the understanding of these systems is limited to endogenous proteins and small molecules used for trafficking of minerals. Phytochelatins, a class of plant-derived metal chelating peptides with the general structure, (γ-Glu-Cys)_n-Gly, are ubiquitous in the diet and were recently found associated with Se and other metals in human urine. These findings suggest that diet-derived phytochelatins could influence metal homeostasis alongside known endogenous metal-binding compounds. In the present study, we investigated the impact of long-term, oral phytochelatin supplementation on metal homeostasis in a murine model. Phytochelatin supplementation increased Se, zinc and cobalt in the liver and increased urinary Se. Integrative analysis of liver metal profiles with untargeted, high-resolution liver metabolomics revealed dynamic metallome interaction with lipid and carbohydrate metabolism. These results highlight an active role of dietary phytochelatins in modulating mammalian metal homeostasis and associated metabolism. Such dietary components could play a pivotal role in regulating trace metal homeostasis and metal-driven pathophysiology.