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Query: UMLS:C0240066 (iron deficiency)
 7,156 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hepcidin, the body's main regulator of systemic iron homeostasis, is upregulated in response to inflammation and is thought to play a role in the manifestation of iron deficiency (ID) observed in obese populations. We determined systemic hepcidin levels and its association with body mass, inflammation, erythropoiesis, and iron status in premenopausal obese and nonobese women (n = 20/group) matched for hemoglobin (Hb). The obese participants also had liver and abdominal visceral and subcutaneous adipose tissue assessed for tissue iron accumulation and hepcidin mRNA expression. Despite similar Hb levels, the obese women had significantly higher serum hepcidin (88.02 vs. 9.70 ng/ml; P < 0.0001) and serum transferrin receptor (sTfR) (P = 0.001) compared to nonobese. In the obese women hepcidin was not correlated with serum iron (r = -0.02), transferrin saturation (Tsat) (r = 0.17) or sTfR (r = -0.12); in the nonobese it was significantly positively correlated with Tsat (r = 0.70) and serum iron (r = 0.58), and inversely with sTfR (r = -0.63). Detectable iron accumulation in the liver and abdominal adipose tissue of the obese women was minimal. Liver hepcidin mRNA expression was ~700 times greater than adipose tissue production and highly correlated with circulating hepcidin levels (r = 0.61). Serum hepcidin is elevated in obese women despite iron depletion, suggesting that it is responding to inflammation rather than iron status. The source of excess hepcidin appears to be the liver and not adipose tissue. The ID of obesity is predominantly a condition of a true body iron deficit rather than maldistribution of iron due to inflammation. However, these findings suggest inflammation may perpetuate this condition by hepcidin-mediated inhibition of dietary iron absorption.
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PMID:Elevated systemic hepcidin and iron depletion in obese premenopausal females. 1981 11

Mild-to-moderate anemia often develops in the setting of acute or chronic immune activation and is termed anemia of chronic disease (ACD) or anemia of inflammation. Anemia of chronic disease is the second most common type of anemia (after anemia of iron deficiency) and results in increased morbidity and mortality of the underlying disease. Anemia of chronic disease is mediated by inflammatory cytokines and is characterized by low serum iron (hypoferremia) and often increased reticuloendothelial stores of iron. Hepcidin is the master regulator of iron homeostasis and its synthesis is inhibited by iron deficiency and stimulated by inflammation. The serum hepcidin level is useful in identifying iron deficiency in patients with ACD. Successful treatment of the underlying disease improves ACD. If that is not possible and if anemia is symptomatic, treatment with erythropoietic agents, supplemented with iron if necessary, is helpful in many cases.
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PMID:Anemia of chronic disease (anemia of inflammation). 1990 47

Hepcidin is the master regulatory hormone of systemic iron metabolism. Hepcidin deficiency causes common iron overload syndromes whereas its overexpression is responsible for microcytic anemias. Hepcidin transcription is activated by the bone morphogenetic protein (BMP) and the inflammatory JAK-STAT pathways, whereas comparatively little is known about how hepcidin expression is inhibited. By using high-throughput siRNA screening we identified SMAD7 as a potent hepcidin suppressor. SMAD7 is an inhibitory SMAD protein that mediates a negative feedback loop to both transforming growth factor-beta and BMP signaling and that recently was shown to be coregulated with hepcidin via SMAD4 in response to altered iron availability in vivo. We show that SMAD7 is coregulated with hepcidin by BMPs in primary murine hepatocytes and that SMAD7 overexpression completely abolishes hepcidin activation by BMPs and transforming growth factor-beta. We identify a distinct SMAD regulatory motif (GTCAAGAC) within the hepcidin promoter involved in SMAD7-dependent hepcidin suppression, demonstrating that SMAD7 does not simply antagonize the previously reported hemojuvelin/BMP-responsive elements. This work identifies a potent inhibitory factor for hepcidin expression and uncovers a negative feedback pathway for hepcidin regulation, providing insight into a mechanism how hepcidin expression may be limited to avoid iron deficiency.
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PMID:SMAD7 controls iron metabolism as a potent inhibitor of hepcidin expression. 2004 Jul 61

Iron deficiency (ID) and iron deficiency anemia (IDA) are the most common iron disorders throughout the world. ID and IDA, particularly caused by increased iron requirements during pregnancy, represent a high risk for preterm delivery, fetal growth retardation, low birth weight, and inferior neonatal health. Oral administration of ferrous sulfate to cure ID and IDA in pregnancy often fails to increase hematological parameters, causes adverse effects and increases inflammation. Recently, we have demonstrated safety and efficacy of oral administration of 30% iron saturated bovine lactoferrin (bLf) in pregnant women suffering from ID and IDA. Oral administration of bLf significantly increases the number of red blood cells, hemoglobin, total serum iron and serum ferritin already after 30 days of the treatment. The increasing of hematological values by bLf is related to the decrease of serum IL-6 and the increase of serum hepcidin, detected as prohepcidin, whereas ferrous sulfate increases IL-6 and fails to increase hematological parameters and prohepcidin. bLf is a more effective and safer alternative than ferrous sulfate for treating ID and IDA in pregnant women.
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PMID:Lactoferrin efficacy versus ferrous sulfate in curing iron deficiency and iron deficiency anemia in pregnant women. 2040 5

The human body cannot actively excrete excess iron. As a consequence, iron absorption must be strictly regulated to ensure adequate iron uptake and prevent toxic iron accumulation. Iron absorption is controlled chiefly by hepcidin, the iron-regulatory hormone. Produced by the liver and secreted into the circulation, hepcidin regulates iron metabolism by inhibiting iron release from cells, including duodenal enterocytes, which mediate the absorption of dietary iron. Hepcidin production increases in response to iron loading and decreases in iron deficiency. Such regulation of hepcidin expression serves to modulate iron absorption to meet body iron demand. This review discusses the proteins that orchestrate hepatic hepcidin production and iron absorption by the intestine. Emphasis is placed on the proteins that directly sense iron and how they coordinate and fine-tune the molecular, cellular, and physiologic responses to iron deficiency and overload.
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PMID:Iron-sensing proteins that regulate hepcidin and enteric iron absorption. 2041 83

Hepcidin is a key hormone governing mammalian iron homeostasis and may be directly or indirectly involved in the development of most iron deficiency/overload and inflammation-induced anemia. The objective of this study was to investigate the expression of hepcidin in anemia of chronic disease. To characterize serum hepcidin, iron and inflammatory indicators associated with anemia of chronic disease (ACD), we studied ACD, ACD concomitant iron-deficiency anemia (ACD/IDA), pure IDA and acute inflammation (AcI) patients and analyzed the associations between hepcidin levels and inflammation parameters in various types of anemia. Serum hepcidin levels in patient groups were statistically different, from high to low: ACD, AcI > ACD/IDA > the control > IDA. Serum ferritin levels were significantly increased in ACD and AcI patients but were decreased significantly in ACD/IDA and IDA. Elevated serum EPO concentrations were found in ACD, ACD/IDA and IDA patients but not in AcI patients and the controls. A positive correlation between hepcidin and IL-6 levels only existed in ACD/IDA, AcI and the control groups. A positive correlation between hepcidin and ferritin was marked in the control group, while a negative correlation between hepcidin and ferritin was noted in IDA. The significant negative correlation between hepcidin expression and reticulocyte count was marked in both ACD/IDA and IDA groups. All of these data demonstrated that hepcidin might play role in pathogenesis of ACD, ACD/IDA and IDA, and it could be a potential marker for detection and differentiation of these anemias.
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PMID:Hepcidin expression in anemia of chronic disease and concomitant iron-deficiency anemia. 2049 29

Iron is an essential trace element in mammalian metabolism. Body iron stores require a tight regulation to avoid detrimental effects due to iron excess or to iron deficiency. Iron losses being not adaptable, iron balance is controlled only through intestinal iron absorption which is regulated by the hepatic peptide hepcidin. Hepcidin synthesis is controlled by several genes including the HFE, hemojuvelin and transferrin receptor 2 genes. Mutations in these genes lead to a phenotype of hemochromatosis. Recently, the bone morphogenetic protein 6 was shown to be the key endogenous ligand involved in the cascade regulating hepcidin synthesis.
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PMID:The iron driven pathway of hepcidin synthesis. 2053 80

Hepcidin expression in vivo is regulated in proportion to iron status (i.e., increased by iron loading and decreased in iron deficiency). However, in vitro studies with hepatoma cell lines often show an inverse relationship between iron status and hepcidin expression. Here, we investigated possible molecular mechanisms responsible for the differences in iron sensing between hepatoma cell lines and human primary hepatocytes. RNA was collected from primary human hepatocytes, and HepG2 and HuH7 hepatoma cells were treated with either transferrin-bound and non-transferrin-bound iron. Expression of hepcidin, transferrin receptor 2, HFE, and hemojuvelin were quantified by real-time PCR. Hepcidin expression was increased in primary human hepatocytes following 24-h exposure to holoferric transferrin. In contrast, hepcidin mRNA levels in hepatoma cells were decreased by transferrin. Hepcidin expression was positively correlated with transferrin receptor 2 mRNA levels in primary human hepatocytes. Compared with primary hepatocytes, transferrin receptor 2 expression was significantly lower in hepatoma cell lines; furthermore, there was no correlation between transferrin receptor 2 and hepcidin mRNA levels in either HepG2 or HuH7 cells. Taken together our data suggest that transferrin receptor 2 is a likely candidate to explain the differences in iron sensing between hepatoma cell lines and primary human hepatocytes.
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PMID:Transferrin receptor 2 is crucial for iron sensing in human hepatocytes. 2057 15

Anemia is a common clinical problem in end-stage renal disease (ESRD). Despite adequate erythropoiesis-stimulating agent (ESA) supplementation, some ESRD patients still have suboptimal hemoglobin levels, and iron deficiency and inflammation are recognized as the two most common causes. Hepcidin, a newly discovered key regulator of iron homeostasis, is found to be accumulated in ESRD. As it controls iron uptake and release, better reflecting real-time iron demand and availability, hepcidin might become a target in the management of iron deficiency and ESA resistance in dialysis patients. For their pleiotropic functions apart from lipid-modulation, statins are also used as anti-inflammatory or immune-modulating agents. In this study, we applied simvastatin for the purpose of influencing serum prohepcidin level in a group of maintenance hemodialysis patients. Thirty-three ESRD patients undergoing hemodialysis were enrolled and assigned to experimental and hemodialysis control groups according to their lipid profile. Nineteen healthy adults were chosen as a normal control group. The subjects in the experimental group took 20 mg simvastatin orally per night for eight weeks, and those in the hemodialysis control group took no statins or any other lipid-modulating drugs. Before and after the experiment, the serum prohepcidin concentrations, plasma IL-6, and serum C-reactive protein (CRP), ferritin, hemoglobin, albumin, total cholesterol, glycerinate, and LDL and HDL cholesterol levels were determined. Of the 33 hemodialysis patients, the serum prohepcidin concentration was (175.8 +/- 52.9) ng/mL, significantly higher than that in the normal control group (149.5 +/- 24.2) ng/mL (P = 0.048). In the experimental group, the serum prohepcidin level was (156.7 +/- 51.9) ng/mL before treatment, and (190.6 +/- 49.6) ng/mL after eight weeks (P = 0.127). In the hemodialysis control group, the serum prohepcidin level was (190.6 +/- 49.6) ng/mL at the beginning, and (193.5 +/- 36.0) ng/mL after eight weeks (P = 0.728). In the experimental group, after taking simvastatin for eight weeks the serum total cholesterol and triglyceride levels had lowered by 18.6% (P = 0.004) and 55.1% (P = 0.007), respectively. The plasma IL-6, serum CRP, ferritin, hemoglobin, albumin, and LDL and HDL cholesterol levels in both the hemodialysis group remained unchanged. According to our preliminary study, eight weeks of 20 mg simvastatin did not significantly change the serum prohepcidin, high-sensitive CRP, or IL-6 concentrations in the group of maintenance hemodialysis patients.
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PMID:How does short-term low-dose simvastatin influence serum prohepcidin levels in patients with end-stage renal disease? A pilot study. 2060 84

Iron metabolism and erythropoiesis are inextricably linked. The majority of iron extracted from circulation daily is used for hemoglobin synthesis. In the last 15 years, major advances have been made in understanding the pathways regulating iron metabolism. Hepcidin is a key regulator of iron absorption and recycling and is itself regulated by erythropoiesis. While several viable candidates have been proposed, elucidating the "erythroid regulator" of hepcidin continues to generate significant experimental activity in the field. Although the mechanism responsible for sensing iron demand for erythropoiesis is still incompletely understood, evaluating diseases in which disordered erythropoiesis and/or iron metabolism are showcased has resulted in a more robust appreciation of potential candidates coordinated erythroid iron demand with regulators of iron supply. We present data drawn from four different conditions-iron deficiency, congenital hypotransferrinemia, beta-thalassemia, and hereditary hemochromatosis-both in human and non-human models of disease, together suggesting that erythroid iron demand exerts a stronger influence on circulating iron supply than systemic iron stores. Greater understanding of the interplay between the key factors involved in the regulation of iron metabolism and erythropoiesis will help develop more effective therapies for disorders of iron overload, iron deficiency, and hemoglobin synthesis.
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PMID:Crosstalk between Iron Metabolism and Erythropoiesis. 2063 98


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