Zinc Supplementation Lowers Hepcidin Levels in the Interleukin-6 Stimulated Caco-2/HepG2 Cell Model

Other conference contribution, 2025

Hepcidin, a key regulator of iron homeostasis, controls iron absorption by promoting the degradation of ferroportin, thereby trapping iron within enterocytes and reducing its transfer into the bloodstream. This process subsequently decreases the activity of both the iron importer divalent metal transporter 1 (DMT1) and the ferric reductase duodenal cytochrome B (Dcytb). In addition to its role in iron regulation, hepcidin also serves as an acute-phase inflammatory mediator. Zinc has been shown to influence hepcidin expression, with zinc deficiency potentially leading to elevated hepcidin levels and exacerbating iron deficiency. This concurrent deficiency of zinc and iron impairs the body's ability to combat infections and inflammation. During inflammation, the circulating cytokine interleukin-6 (IL-6) increases the expression of the zinc importer ZRT/IRT-like protein 14 (ZIP14) in liver cells, inducing hypozincemia, and at the same time raising hepcidin levels, inducing hypoferremia.

This study aimed to investigate the interaction between zinc and iron homeostasis, specifically focusing on zinc supplementation on the regulation of zinc transporters, hepcidin, and ferroportin expression in an intestinal and hepatic co-culture model, particularly under inflammatory conditions induced by IL-6. This could provide mechanistic insights into the therapeutic potential of zinc supplementation in managing iron deficiency during inflammation.