Figure 3.

Hypothetical model for direct and indirect effects of zinc on intestinal iron absorption and iron homeostasis: During adequate zinc status and dietary intakes, the biliary-pancreatic zinc secreted into the intestinal lumen stimulates the intestinal iron transport via PI3K-IRP2-DMT1 and FPN1. During inadequate zinc intake, reduced pancreatic zinc levels reduces intestinal iron transporter DMT1 and FPN1 expression, leading to increased retention and inhibition of absorption. Similarly, excretion of zinc from tissues such as liver and bone marrow results in declined tissue zinc, and as a consequence reduced FPN1 expression, leading to reduced secretion for erythropoietic needs. Alternately, zinc might prevent inflammation and thus negate its inhibitory effect on iron absorption. During zinc sufficiency, growth signaling mediated by mTORC1 pathway might increase the iron requirements and thus improve iron absorption.