Hepcidin: Maintaining Iron Balance in Your BodyKaplan says iron balance in the human body is regulated by hepcidin, which is a peptide hormone secreted to help metabolize iron that we eat. Hepcidin attaches or "binds" to a substance named ferroportin, which exports iron from cells into the blood."High levels of hepcidin in the blood results in the loss of ferroportin from cells, leading to decreased export of iron from cells to blood," Kaplan says.If too little iron in the blood persists, a person has anemia."Usually when you take an iron pill or you get a bacterial infection that is self-limiting, you'll get an increase in hepcidin, which in time will decrease," says Kaplan. "As hepcidin binds to ferroportin, it removes ferroportin from the blood and also removes hepcidin from the blood. Both are degraded in the cells."The opposite of anemia is iron overload, and "most diseases of iron overload result from not enough hepcidin to remove ferroportin from cells," he adds. Ferroportin brings iron from our diet into the blood, so without enough hepcidin, too much iron accumulates in the blood."Hepcidin monitors your body's iron status," Kaplan says. "When you have too much iron, hepcidin increases to help prevent more iron from coming in. When you need more iron, hepcidin levels decrease, permitting more iron to come into the body from your diet and from iron stored in your cells, particularly your spleen."In a series of previous studies, Kaplan and colleagues worked out how hepcidin causes ferroportin to be carried into cells and degraded.They discovered an enzyme named Jak2 changes or "phosphorylates" ferroportin so it can be carried into cells to be degraded.In the new study, they showed the same Jak2 enzyme also phosphorylates or adds a phosphate molecule to Stat3, which is a protein that turns various genes on or off. In other words, Jak2 makes it possible for Stat3 to turn genes on or off.The new study shows that "among the genes that are turned on are genes that reduce inflammation," Kaplan says.Yet only a couple of the genes activated by Stat3 involve inflammation. What the rest of them do isn't known. So it's possible the iron metabolism process involving hepcidin, ferroportin, Jak2 and Stat3 may be involved in other processes in the body.

A Mystery of EvolutionWhy would a hormone that regulates iron balance also combat inflammation?"Our view is that this is a feedback system, so anytime in your body when you turn on a gene, there's always a mechanism by which you can turn it off or limit it," Kaplan says. "So here's a case where bacteria come in, turn on inflammation, and this hepcidin pathway we discovered is a way of limiting that. Inflammation is good, but too much inflammation is bad. So here is a way of regulating inflammation."But, he adds, "How an antibacterial agent got to regulate iron and then got to reduce inflammation is one of the mysteries of evolution."SOURCE University of Utah