scholarly journals Serum prohepcidin concentration: no association with iron absorption in healthy men; and no relationship with iron status in men carrying HFE mutations, hereditary haemochromatosis patients undergoing phlebotomy treatment, or pregnant women

2007 ◽  
Vol 97 (3) ◽  
pp. 544-549 ◽  
Author(s):  
Mark A. Roe ◽  
Caroline Spinks ◽  
Anne-Louise M. Heath ◽  
Linda J. Harvey ◽  
Rob Foxall ◽  
...  
Keyword(s):  
Pregnant Women ◽  
Iron Homeostasis ◽  
Iron Absorption ◽  
Iron Status ◽  
Red Cell ◽  
Wild Type ◽  
Hereditary Haemochromatosis ◽  
Healthy Men ◽  
Hfe Mutations ◽  
Potential Use

Hepcidin plays a major role in iron homeostasis, but understanding its role has been hampered by the absence of analytical methods for quantification in blood. A commercial ELISA has been developed for serum prohepcidin, a hepcidin precursor, and there is interest in its potential use in the clinical and research arena. We investigated the association between serum prohepcidin concentration and iron absorption in healthy men, and its relationship with iron status in men carrying HFE mutations, hereditary haemochromatosis patients, and pregnant women. Iron absorption was determined in thirty healthy men (fifteen wild-type, fifteen C282Y heterozygote) using the stable isotope red cell incorporation technique. Iron status was measured in 138 healthy men (ninety-one wild-type, forty-seven C282Y heterozygote), six hereditary haemochromatosis patients, and thirteen pregnant women. Mean serum prohepcidin concentrations were 214 (sd 118) ng/ml [208 (sd 122) ng/ml in wild-type and 225 (sd 109) ng/ml in C282Y heterozygotes] in healthy men, 177 (sd 36) ng/ml in haemochromatosis patients, and 159 (sd 59) ng/ml in pregnant women. There was no relationship between serum prohepcidin concentration and serum ferritin in any subject groups, nor was it associated with efficiency of iron absorption. Serum prohepcidin is not a useful biomarker for clinical or research purposes.

scholarly journals Interrelationships between circulating gastrin and iron status in mice and humans

2008 ◽  
Vol 295 (4) ◽  
pp. G855-G861 ◽  
Author(s):  
Suzana Kovac ◽  
Kelly Smith ◽  
Gregory J. Anderson ◽  
John R. Burgess ◽  
Arthur Shulkes ◽  
...  
Keyword(s):  
Iron Homeostasis ◽  
Iron Absorption ◽  
Iron Status ◽  
Transferrin Saturation ◽  
Wild Type ◽  
Liver Iron ◽  
Divalent Metal Transporter 1 ◽  
Divalent Metal Transporter ◽  
Mrna Concentration

The observations that the peptide hormone gastrin interacts with transferrin in vitro and that circulating gastrin concentrations are increased in the iron-loading disorder hemochromatosis suggest a possible link between gastrin and iron homeostasis. This study tested the hypothesis that gastrin and iron status are interrelated by measurement of iron homeostasis in mice and humans with abnormal circulating gastrin concentrations. Intestinal iron absorption was determined by59Fe uptake following oral gavage, and concentrations of duodenal divalent metal transporter-1 (DMT-1) and hepatic hepcidin mRNAs were determined by quantitative real-time PCR in agastrinemic (GasKO), hypergastrinemic cholecystokinin 2 receptor-deficient (CCK2RKO), or wild-type mice. Iron status was measured by standard methods in the same mice and in hypergastrinemic humans with multiple endocrine neoplasia type 1 (MEN-1). Iron absorption was increased sixfold and DMT-1 mRNA concentration fourfold, and transferrin saturation was reduced 0.8-fold and hepcidin mRNA expression 0.5-fold in juvenile GasKO mice compared with age-matched wild-type mice. In mature mice, few differences were observed between the strains. Juvenile CCK2RKO mice were hypergastrinemic and had a 5.4-fold higher DMT-1 mRNA concentration than wild-type mice without any increase in iron absorption. In contrast to juvenile GasKO mice, juvenile CCK2RKO mice had a 1.5-fold greater transferrin saturation, which was reflected in a twofold increase in liver iron deposition at maturity compared with wild-type mice. The correlation between transferrin saturation and circulating gastrin concentration observed in mutant mice was also observed in human patients with MEN, in whom hypergastrinemia correlated positively ( P = 0.004) with an increased transferrin saturation. Our data indicate that, in juvenile animals when iron demand is high, circulating gastrin concentrations may alter iron status by a CCK2R-independent mechanism.

scholarly journals Hepcidin: A Critical Regulator of Iron Metabolism during Hypoxia

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Korry J. Hintze ◽  
James P. McClung
Keyword(s):  
Iron Metabolism ◽  
Iron Homeostasis ◽  
Molecular Mechanisms ◽  
Iron Absorption ◽  
Iron Acquisition ◽  
Iron Status ◽  
Hypoxia Inducible Factor ◽  
Hypoxia Response Element ◽  
Hypoxia Response ◽  
Hepcidin Expression

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. 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. This paper will focus on the molecular mechanisms by which hypoxia affects hepcidin expression, to include a review of the hypoxia inducible factor (HIF)/hypoxia response element (HRE) system, as well as recent evidence indicating that localized adipose hypoxia due to obesity may affect hepcidin signaling and organismal iron metabolism.

scholarly journals Role of Dietary Flavonoids in Iron Homeostasis

2019 ◽  
Vol 12 (3) ◽  
pp. 119 ◽  
Author(s):  
Marija Lesjak ◽  
Surjit K. S. Srai
Keyword(s):  
Iron Metabolism ◽  
Iron Homeostasis ◽  
Iron Absorption ◽  
Therapeutic Potential ◽  
State Of The Art ◽  
Iron Status ◽  
Dietary Factors ◽  
The Body ◽  
Dietary Flavonoids

Balancing systemic iron levels within narrow limits is critical for human health, as both iron deficiency and overload lead to serious disorders. There are no known physiologically controlled pathways to eliminate iron from the body and therefore iron homeostasis is maintained by modifying dietary iron absorption. Several dietary factors, such as flavonoids, are known to greatly affect iron absorption. Recent evidence suggests that flavonoids can affect iron status by regulating expression and activity of proteins involved the systemic regulation of iron metabolism and iron absorption. We provide an overview of the links between different dietary flavonoids and iron homeostasis together with the mechanism of flavonoids effect on iron metabolism. In addition, we also discuss the clinical relevance of state-of-the-art knowledge regarding therapeutic potential that flavonoids may have for conditions that are low in iron such as anaemia or iron overload diseases.

Intestinal Iron Absorption: Regulation by Dietary & Systemic Factors

2010 ◽  
Vol 80 (45) ◽  
pp. 231-242 ◽  
Author(s):  
Paul A. Sharp
Keyword(s):  
Iron Homeostasis ◽  
Iron Absorption ◽  
Iron Status ◽  
Heme Iron ◽  
Dietary Factors ◽  
The Body ◽  
Excess Iron ◽  
Non Heme Iron ◽  
Systemic Factors ◽  
And Function

Iron is an essential trace metal in human metabolism. However, imbalances in iron homeostasis are prevalent worldwide and have detrimental effects on human health. Humans do not have the ability to remove excess iron and therefore iron homeostasis is maintained by regulating the amount of iron entering the body from the diet. Iron is present in the human diet in number of different forms, including heme (from meat) and a variety of non-heme iron compounds. While heme is absorbed intact, the bioavailability of non-heme iron varies greatly depending on dietary composition. A number of dietary components are capable of interacting with iron to regulate its solubility and oxidation state. Interestingly, there is an emerging body of evidence suggesting that some nutrients also have direct effects on the expression and function of enterocyte iron transporters. In addition to dietary factors, body iron status is a major determinant of iron absorption. The roles of these important dietary and systemic factors in regulating iron absorption will be discussed in this review.

Erythroid Growth Differentiation Factor 15 and Ferroportin Expression During Gestational Iron Deficiency Anemia

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 5286-5286
Author(s):  
Rekha Athiyarath ◽  
Kalaiselvi Sakthivel ◽  
Vinod J Abraham ◽  
Daisy Singh ◽  
Alok Srivastava ◽  
...  
Keyword(s):  
Gene Expression ◽  
Iron Deficiency ◽  
Pregnant Women ◽  
Iron Deficiency Anemia ◽  
Iron Homeostasis ◽  
Iron Absorption ◽  
Deficiency Anemia ◽  
Protein Levels ◽  
In Pregnancy

Abstract Abstract 5286 Iron homeostasis during pregnancy is modulated to meet the increased iron needs but how this is achieved is not very clear. Growth Differentiation Factor (GDF15) produced by the expanded erythroid compartment in β thalassemia has been shown to increase iron absorption by suppressing hepcidin. GDF15 is also highly expressed in the placenta and increasing levels of GDF15 are seen with advancing gestational age of pregnancy. But the role of GDF15 in iron homeostasis in pregnancy has not been elucidated till date. Ferroportin (FPN) is the only known protein involved in iron export and it is the target of hepcidin, the central regulator of iron homeostasis. In this study we analyzed the expression of GDF15 and FPN in pregnant women with iron deficiency anemia. Fourteen pregnant women with proven iron deficiency anemia (IDAP) [Hb<11g/dL and Ferritin <12ng/ul] and thirteen healthy subjects as controls (NC) were enrolled as part of an ongoing study. Serum GDF15 and hepcidin levels were measured by ELISA kits from R&D systems and Bachem, UK respectively. Reticulocytes were isolated and total RNA was purified using Trizol. GDF15 and FPN transcripts were quantified using Taqman Gene expression assays using GAPDH as an internal control. Gene expression values were calculated on the basis of the 2-ΔΔCt method. The mean age of the pregnant women was 22.5±2.5 years. The median ferritin in IDAP was 1.4 and ranged from 0.2 to 8.3 ng/ml. The hepcidin levels were very low [<2ng/ml] in IDAP. Serum GDF15 levels in IDAP was significantly higher as compared to controls [IDAP-3333.71±409 pg/ml vs. NC-309.7±127.0 pg/ml; p=0.000]. Reticulocyte GDF15 mRNA expression was significantly lower [IDAP-25.09 (1.28–239.8) vs. NC-910.4 (0.28–1962); p=0.004] and FPN expression was significantly higher in pregnancy [IDAP-209.8 (48.33–1201) vs. NC-77.96(17.21–281.3); p=0.001] than in the controls. GDF15 mRNA as well as serum GDF15 levels significantly correlated with FPN expression in IDAP [RNA r=0.895; p=0.000; Protein r=0.555, p=0.049] Eight patients were followed up after 8 weeks of supplementation and there was no significant change in the serum GDF15 concentration (3235±468.26pg/ml; p=1.000). However their serum ferritin and hepcidin levels were significantly higher [Ferritin-11.60 (9.80–21.30), p=0.0021; Hepcidin-17.86(0.29–38.50), p=0.015]. There was no significant correlation between GDF15 protein levels and hepcidin (r=0.429, p=0.354). Molecular mechanisms of iron homeostasis in pregnancy are poorly understood. IDAP had very low hepcidin levels which normalized after iron stores were replenished. Elevated GDF15 protein levels in IDAP inspite of low reticulocyte expression indicate that erythroid contribution is minimal and placenta is the main source of GDF15. The significant correlation between GDF15 (mRNA and protein) with FPN expression and absence of correlation with hepcidin levels indicate a possible role for GDF15 in iron homeostasis in pregnancy. These findings has to be validated and the role of GDF15 in modulating FPN and there by iron absorption has to be further elucidated. Disclosures: No relevant conflicts of interest to declare.

Iron Imports. VI. HFE and regulation of intestinal iron absorption

2006 ◽  
Vol 290 (4) ◽  
pp. G590-G594 ◽  
Author(s):  
Robert E. Fleming ◽  
Robert S. Britton
Keyword(s):  
Iron Homeostasis ◽  
Iron Absorption ◽  
Iron Status ◽  
Hfe Gene ◽  
Primary Role ◽  
Intestinal Iron Absorption ◽  
Downstream Effects ◽  
Cell Type Specific ◽  
Intestinal Enterocytes

The majority of clinical cases of iron overload is caused by mutations in the HFE gene. However, the role that HFE plays in the physiology of intestinal iron absorption remains enigmatic. Two major models have been proposed: 1) HFE exerts its effects on iron homeostasis indirectly, by modulating the expression of hepcidin; and 2) HFE exerts its effects directly, by changing the iron status (and therefore the iron absorptive activity) of intestinal enterocytes. The first model places the primary role of HFE in the liver (hepatocytes and/or Kupffer cells). The second model places the primary role in the duodenum (crypt cells or villus enterocytes). These models are not mutually exclusive, and it is possible that HFE influences the iron status in each of these cell populations, leading to cell type-specific downstream effects on intestinal iron absorption and body iron distribution.

scholarly journals Relationship between gene expression of duodenal iron transporters and iron stores in hemochromatosis subjects

2010 ◽  
Vol 298 (1) ◽  
pp. G57-G62 ◽  
Author(s):  
James E. Nelson ◽  
Virginia R. Mugford ◽  
Ellen Kilcourse ◽  
Richard S. Wang ◽  
Kris V. Kowdley
Keyword(s):  
Gene Expression ◽  
Iron Overload ◽  
Iron Transport ◽  
Iron Absorption ◽  
Hereditary Hemochromatosis ◽  
Phenotypic Expression ◽  
Wild Type ◽  
Significant Difference ◽  
Hfe Mutations ◽  
Relative Gene

To test the hypothesis that differences in duodenal iron absorption may explain the variable phenotypic expression among HFE C282Y homozygotes, we have compared relative gene expression of duodenal iron transporters among C282Y homozygotes [hereditary hemochromatosis (HH)] with and without iron overload. Duodenal biopsy samples were analyzed using real-time PCR for expression of DMT1, FPN1, DCYTB, and HEPH relative to GAPDH from 23 C282Y homozygotes, including 5 “nonexpressors” (serum ferritin < upper limit of normal and absence of phenotypic features of hemochromatosis) and 18 “expressors.” Four subjects of wild type for HFE mutations without iron overload or liver disease served as controls. There was a significant difference in expression of DMT1 ( P = 0.03) and DMT1(IRE) ( P = 0.0013) but not FPN1, DCYTB, or HEPH between groups. Expression of DMT1(IRE) was increased among HH subjects after phlebotomy compared with untreated ( P = 0.006) and nonexpressor groups ( P = 0.026). A positive relationship was observed among all HH subjects regardless of phenotype or treatment status between relative expression of FPN1 and DMT1 ( r = 0.5854, P = 0.0021), FPN1, and DCYTB ( r = 0.5554, P = 0.0040), FPN1 and HEPH ( r = 0.5100, P = 0.0092), and DCYTB and HEPH ( r = 0.5400, P = 0.0053). In summary, phlebotomy is associated with upregulation of DMT1(IRE) expression in HH subjects. HFE C282Y homozygotes without phenotypic expression do not have significantly decreased duodenal gene expression of iron transport genes compared with HH subjects with iron overload. There is coordinated regulation between duodenal expression of FPN1 and DMT1, FPN1 and DCYTB, and FPN1 and HEPH and also DCYTB and HEPH in HH subjects regardless of phenotype.

Compared to Normal-Weight Pregnant Women, Overweight Pregnant Women Fail to Upregulate Iron Absorption in the Third Trimester Despite Iron Deficiency and Their Infants Are Born with Lower Body Iron Stores

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 51-52
Author(s):  
Nicole Ursula Stoffel ◽  
Michael Bruce Zimmermann ◽  
Ana Carla Cepeda Lopez ◽  
Karla I Cervantes Gracia ◽  
Elida E Lee Bazaldua ◽  
...  
Keyword(s):  
Pregnant Women ◽  
Iron Supplementation ◽  
Iron Absorption ◽  
Iron Status ◽  
Normal Weight ◽  
Lower Body ◽  
Iron Transfer ◽  
Significant Group ◽  
Iron Stores ◽  
The Impact

Introduction: Overweight/obesity (OWOB) causes low-grade systemic inflammation which induces hepcidin and a reduces fractional iron absorption (FIA) even when iron stores are low. Pregnancy increases iron needs because of the expansion of maternal blood volume and fetal needs. It is unclear whether and/or to what extent OWOB during pregnancy influences FIA, iron supply of the fetus and risk of iron deficiency in mother and newborn. In this study, we (1) determined the impact of maternal OWOB on FIA in pregnancy and on the transfer of iron to the fetus and newborn iron status; (2) confirmed the relationship between BMI, hepcidin, serum ferritin (SF) and inflammatory markers. Methods: In this prospective experimental multi-center case-control study (normal-weight (NW) n=40; OWOB n=37) we administered labeled [57Fe]- or [58Fe]-FeSO4 to women during the 2nd and 3rd trimester of pregnancy. We measured FIA by determining erythrocyte incorporation of iron stable isotopes 14 days after administration. From pregnancy week (PW) 12 until PW 36, iron-, inflammation and hepcidin were monitored. Iron transfer to the fetus was determined isotopically as the concentration of circulating iron in the infant aged three days. We assessed iron status in infants born to NW (n=29) and OWOB (n=31) at age three days, three months and six months. Results: Subject characteristics in PW 12 for the NW/OWOB were: mean (±SD) age: 29±6/ 30±6 years, median (IQR) pre-pregnancy BMI: 21.6 (20.3-23.7)/ 31.6 (28.4-35.9) kg/m2 (p&lt;0.001), mean (±SD) hemoglobin: 12.3±1.1/ 12.4±0.9 g/dL, median (IQR) SF: 27.7 (17.3-48.2)/ 30.6 (16.6-64.4) µg/L and median (IQR) interleukin-6: 1.41 (1.03-1.95)/ 2.37 (1.91-3.85) pg/ml (p&lt;0.001). Independent sample t-test showed no difference in FIA between NW and OWOB in the 2nd trimester with median FIA (IQR) 12.3 (7.2-20.6) and 10.1 (6.9-17.2) % (p=0.788). Despite the OWOB had ≈30% lower body iron stores (BIS) and comparable hepcidin concentrations to the NW in the 3rd trimester, FIA was significantly higher in the NW compared to the OWOB with median FIA (IQR) 22.3 (10.6-33.8) and 12.7 (10.4-18.1) % (p=0.042). In the NW, FIA was upregulated by 80% in the 3rd trimester compared to the 2nd trimester, whereas in the OWOB FIA, it was only upregulated by 25%. Linear mixed effect model analysis (LMM) showed a significant group-effects on weight, IL-6 and CRP throughout pregnancy (all p&lt;0.05), but surprisingly no group-effect on hepcidin. In multiple regression analysis, the main predictor of hepcidin throughout pregnancy was BIS, not inflammation. Iron transfer to the newborn was non-significantly higher in the NW compared to the OWOB with mean (±SD) circulating iron in the newborn at age three days 136.6 ± 42.7 and 126.3 ± 32.4 mg. LMM on infant BIS and on infant serum transferrin receptor (sTfR) over the first six months showed significant group (p=0.024, p=0.046) and time-effects (both p&lt;0.001) with lower BIS and higher sTfR in infants born to OWOB. Median (IQR) BIS at age six months were 7.7 (6.3-8.8) and 6.6 (4.6-9.2) mg/kg bodyweight in infants born to NW and OWOB. Conclusion: In normal pregnancy, FIA increases over time to support increased iron needs of mother and fetus. Our data show a dramatically reduced increase in FIA in OWOB pregnant women in the 3rd trimester, despite low BIS and low hepcidin, and this results in less iron transfer to the fetus. Future molecular studies are needed to clarify the mechanism of reduced FIA and fetal iron transfer in OWOB. To our knowledge, this is the first study assessing the impact of maternal OWOB on infant iron status at multiple time points over the first six months. Our findings strongly argue for careful monitoring of iron status in OWOB pregnancy and for defining a more effective iron supplementation regimen for this population group. Prevalence of anemia in pregnancy and infancy is high, especially in low and middle income countries and is often associated with severe health consequences. If iron status of OWOB pregnant women and their infants could be improved by optimizing iron supplementation guidelines for OWOB, this could have major benefits. Disclosures No relevant conflicts of interest to declare.

scholarly journals Hepcidin and Iron Deficiency in Women One Year after Sleeve Gastrectomy: A Prospective Cohort Study

Nutrients ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 2516
Author(s):  
Thibaud Lefebvre ◽  
Muriel Coupaye ◽  
Marina Esposito-Farèse ◽  
Nathalie Gault ◽  
Neila Talbi ◽  
...  
Keyword(s):  
Sleeve Gastrectomy ◽  
Iron Deficiency ◽  
Iron Supplementation ◽  
Iron Homeostasis ◽  
Iron Absorption ◽  
Iron Status ◽  
Obese Women ◽  
Serum Hepcidin ◽  
One Year ◽  
The Impact

Iron deficiency with or without anemia, needing continuous iron supplementation, is very common in obese patients, particularly those requiring bariatric surgery. The aim of this study was to address the impact of weight loss on the rescue of iron balance in patients who underwent sleeve gastrectomy (SG), a procedure that preserves the duodenum, the main site of iron absorption. The cohort included 88 obese women; sampling of blood and duodenal biopsies of 35 patients were performed before and one year after SG. An analysis of the 35 patients consisted in evaluating iron homeostasis including hepcidin, markers of erythroid iron deficiency (soluble transferrin receptor (sTfR) and erythrocyte protoporphyrin (PPIX)), expression of duodenal iron transporters (DMT1 and ferroportin) and inflammatory markers. After surgery, sTfR and PPIX were decreased. Serum hepcidin levels were increased despite the significant reduction in inflammation. DMT1 abundance was negatively correlated with higher level of serum hepcidin. Ferroportin abundance was not modified. This study shed a new light in effective iron recovery pathways after SG involving suppression of inflammation, improvement of iron absorption, iron supply and efficiency of erythropoiesis, and finally beneficial control of iron homeostasis by hepcidin. Thus, recommendations for iron supplementation of patients after SG should take into account these new parameters of iron status assessment.

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