Hepcidin and Iron relationship

Hepcidin is getting attention as a new important factor in iron homeostasis especially in the brain. it is a small peptide hormone with antimicrobial properties and iron regulatory responsibility.
iron balance is strictly regulated through a series of cellular transport proteins that are sensitive to hepcidin.

hepcidin is a 25-amino-acid peptide and is the principal regulator of iron absorption and its distribution to tissues. Hepcidin is synthesized predominantly in hepatocytes, but its low levels of expression in other cells and tissues, including macrophages, adipocytes and brain, may also be important for the autocrine and paracrine control of iron fluxes at the local level.

roles for hepcidin in both the acquisition of iron from the gastrointestinal tract and the efflux of iron from macrophages have been characterized.

Iron functions biochemically through incorporation into a series of proteins and enzymes. Many of these proteins and enzymes, including myoglobin, cytochrome c and hemoglobin, are required for optimal cognitive and physical performance in humans
studies have demonstrated a link between obesity and poor iron status. they showed this association in children, adult men and women and even postmenopausal women. Obesity has been suggested as an independent factor contributing to iron deficiency, and studies have correlated obesity, BMI, and increased hepcidin in premenopausal women and children. Chronic inflammation is associated with central obesity and has been implicated in many obesity-related problems such as insulin resistance.
Although the contribution of dietary sources to iron balance should not be ignored, hepcidin has been described as the “central regulator of iron homoeostasis” and affects both iron absorption through the duodenal enterocyte and iron export from the macrophage and other iron exporting cells. Further, a series of factors, some of which are not directly associated with dietary iron intake, affect hepcidin levels, such as inflammation, erythropoiesis, and hypoxia.

The term hypoxia is a condition where the tissues are not oxygenated adequately, usually due to an insufficient concentration of oxygen in the blood.

Hypoxia has profound effects on iron absorption and results in increased iron acquisition and erythropoiesis when humans move from sea level to altitude. The effects of hypoxia on iron balance have been attributed to hepcidin, a central regulator of iron homeostasis.
Research in the area of hypoxia and iron metabolism continues to provide good evidence of the molecular regulation of hepcidin and its effects on iron status.
Iron status affects cognitive and physical performance in humans. Recent evidence indicates that iron balance is a tightly regulated process affected by a series of factors other than diet, to include hypoxia.
Iron balance has been historically defined as the net difference between the amount of iron that is absorbed from the diet and the amount of iron that is excreted. As such, countless investigations have focused on dietary factors affecting iron balance, such as the quantity of iron found in particular food sources and factors that may promote or inhibit iron absorption. Although iron consumption through the diet is clearly a major determinant of iron status, it has become increasingly apparent that many factors affect iron balance.
Although the prevalence of iron deficiency and iron deficiency anemia is greatest in the developing world, poor iron status also affects a significant portion of the population in developed nations. For example, iron deficiency and iron deficiency anemia affect up to 12 and 4% of premenopausal women in the United States, respectively.
Although diminished work capacity due to reduced hemoglobin levels is the best described functional consequence of poor iron status, other outcomes include diminished intellectual performance, altered body temperature regulation, reduced immunity and resistance to infections.
Studies suggest that there are two sources of hepcidin in the brain: one is local and the other comes from the circulation. Little is known about the molecular mediators of local hepcidin expression, but inflammation and iron-load have been shown to induce hepcidin expression in the brain. The most important source of hepcidin in the brain are glial cells. Role of hepcidin in brain functions has been observed during neuronal iron-load and brain hemorrhage, where secretion of abundant hepcidin is related with the severity of brain damage. This damage can be reversed by blocking systemic and local hepcidin secretion. Studies have yet to unveil its role in other brain conditions, but the rationale exists, since these conditions are characterized by overexpression of the factors that stimulate brain hepcidin expression, such as inflammation, hypoxia and iron-overload.
When kidney function is normal, urinary hepcidin concentrations correlate well with circulating hepcidin levels, with no apparent regulation of the excretion process. However, based on the comparison between serum and urinary concentrations, it appears that only 5% of hepcidin from plasma filtered in the kidneys ends up intact in the urine.