Food deprivation increases hepatic hepcidin expression and can overcome the effect of Hfe deletion in male mice

What is it about?

The maintenance of body iron levels is crucial for human health. If a person has either too little or too much iron, disease can result. Most iron deficiency is caused by insufficient iron in the diet, but most iron loading is caused by mutations in genes regulating dietary iron absorption, so that a person cannot effectively control how much iron they take in. These iron loading diseases are known as different forms of hemochromatosis, and they are characterized by reduced production of the hormone hepcidin. Hepcidin inhibits dietary iron absorption, so when its levels are low, absorption is increased. Mutations in the HFE gene lead to low hepcidin levels and, consequently, hemochromatosis. HFE-hemochromatosis is a common disease, affecting approximately 1 in 200 people of Caucasian descent, but there is currently no way to increase hepcidin levels in these patients. However, recent studies have suggested that food deprivation can increase hepcidin production both in humans and in mice. To examine whether this effect might be harnessed to treat iron loading disorders, we examined the effects of food deprivation in a mouse model of HFE-hemochromatosis. We found that food deprivation could increase hepcidin in these animals despite the Hfe gene being non-functional. These results imply that the induction of hepcidin by food deprivation occurs via a pathway that is independent of HFE, and suggest that targeting this pathway using drugs could be prove an effective treatment for iron-loading conditions such as hemochromatosis.

Featured Image