Systemic iron homeostasis in female athletes: hepcidin, exercise and sex influence

Iron is necessary for adequate deliver oxygen to the tissues since it is an essential component of the haemoglobin. However, iron deficiency remains a common problem among athletes, particularly for women experiencing the menstrual bleeding every month. The iron losses through menstrual blood loss during the early follicular phase (or menses) and an inadequate dietary intake of iron are two important factors contributing to this disease. Furthermore, the large hormonal changes that women experience along the menstrual cycle, especially in oestrogen and progesterone may influence on the optimization of iron absorption. Iron absorption is mainly mediated by hepcidin hormone, which seems to be affected by several stimulus and factors such as oestrogen and progesterone concentrations. Moreover, the regular practice of exercise is another important modulator of this hormone. Therefore, premenopausal active females are the most susceptible population to develop an iron deficiency or iron deficiency anemia, affecting their health and performance due to the less iron availability within the body and consequently a reduction of haemoglobin which compromise the oxygen transport. To date, most studies have not explored the acute post-exercise hepcidin response taking endogenous and exogenous sexual hormones influence into account. This narrative review will focus on how iron homeostasis is modulated by different factors mainly influenced by exercise and female sexual hormones.

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Iron Homeostasis and Disorders in Dogs and Cats: A Review

Journal of the American Animal Hospital Association ◽

10.5326/jaaha-ms-5553 ◽

2011 ◽

Vol 47 (3) ◽

pp. 151-160 ◽

Cited By ~ 27

Author(s):

Jennifer L. McCown ◽

Andrew J. Specht

Keyword(s):

Iron Deficiency ◽

Iron Overload ◽

Iron Homeostasis ◽

Diagnostic Testing ◽

Clinical Manifestations ◽

Essential Element ◽

The Body ◽

Deficiency Anemia ◽

Enzyme Systems ◽

Living Organisms

Iron is an essential element for nearly all living organisms and disruption of iron homeostasis can lead to a number of clinical manifestations. Iron is used in the formation of both hemoglobin and myoglobin, as well as numerous enzyme systems of the body. Disorders of iron in the body include iron deficiency anemia, anemia of inflammatory disease, and iron overload. This article reviews normal iron metabolism, disease syndromes of iron imbalance, diagnostic testing, and treatment of either iron deficiency or excess. Recent advances in diagnosing iron deficiency using reticulocyte indices are reviewed.

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Modulation of the HIF2-NCOA4 axis in enterocytes attenuates iron loading in a mouse model of hemochromatosis

Blood ◽

10.1182/blood.2021013452 ◽

2022 ◽

Author(s):

Nupur K Das ◽

Chesta Jain ◽

Amanda D. Sankar ◽

Andrew J Schwartz ◽

Naiara Santana-Codina ◽

...

Keyword(s):

Iron Deficiency ◽

Mouse Model ◽

Iron Overload ◽

Iron Homeostasis ◽

Iron Absorption ◽

Hypoxia Inducible Factor ◽

Whole Body ◽

Deficiency Anemia ◽

Null Mouse ◽

Intestinal Iron Absorption

Intestinal iron absorption is activated during increased systemic iron demand. The best-studied example is iron-deficiency anemia, which increases intestinal iron absorption. Interestingly, the intestinal response to anemia is very similar to that of iron overload disorders, as both the conditions activate a transcriptional program that leads to a hyperabsorption of iron via the transcription factor hypoxia-inducible factor (HIF)2a. However, pathways to selectively target intestinal-mediated iron overload remain unknown. Nuclear receptor co-activator 4 (NCOA4) is a critical cargo receptor for autophagic breakdown of ferritin (FTN) and subsequent release of iron, in a process termed ferritinophagy. Our work demonstrates that NCOA4-mediated intestinal ferritinophagy is integrated to systemic iron demand via HIF2a. To demonstrate the importance of intestinal HIF2a/ferritinophagy axis in systemic iron homeostasis, whole body and intestine-specific NCOA4-null mouse lines were generated and assessed. These analyses revealed that the intestinal and systemic response to iron deficiency was not altered following disruption of intestinal NCOA4. However, in a mouse model of hemochromatosis, ablation of intestinal NCOA4 was protective against iron overload. Therefore, NCOA4 can be selectively targeted for the management of iron overload disorders without disrupting the physiological processes involved in the response to systemic iron deficiency.

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Molecular Mechanisms Regulating Hepcidin Revealed by Hepcidin Disorders

The Scientific World JOURNAL ◽

10.1100/tsw.2011.130 ◽

2011 ◽

Vol 11 ◽

pp. 1357-1366 ◽

Cited By ~ 17

Author(s):

Clara Camaschella ◽

Laura Silvestri

Keyword(s):

Iron Deficiency ◽

Iron Overload ◽

Transcriptional Control ◽

Iron Homeostasis ◽

Molecular Mechanisms ◽

Human Life ◽

Genetic Diseases ◽

The Body ◽

Deficiency Anemia ◽

Iron Regulatory Proteins

Iron is essential for human life, but toxic if present in excess. To avoid iron overload and maintain iron homeostasis, all cells are able to regulate their iron content through the post-transcriptional control of iron genes operated by the cytosolic iron regulatory proteins that interact with iron responsive elements on iron gene mRNA. At the systemic level, iron homeostasis is regulated by the liver peptide hepcidin. Disruption of these regulatory loops leads to genetic diseases characterized by iron deficiency (iron-refractory iron-deficiency anemia) or iron overload (hemochromatosis). Alterations of the same systems are also found in acquired disorders, such as iron-loading anemias characterized by ineffective erythropoiesis and anemia of chronic diseases (ACD) associated with common inflammatory conditions. In ACD, iron is present in the body, but maldistributed, being deficient for erythropoiesis, but sequestered in macrophages. Studies of the hepcidin regulation by iron and inflammatory cytokines are revealing new pathways that might become targets of new therapeutic intervention in iron disorders.

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DEVELOPMENT OF A SPECIALIZED FOOD PRODUCT FOR THE PREVENTION OF IRON DEFICIENCY ANEMIA IN JUNIOR ATHLETES

10.47501/978-5-6044060-1-4.34 ◽

2021 ◽

Author(s):

Irina Vitalievna Kobelkova ◽

◽

Margarita Mikhailovna Korosteleva ◽

Dmitry Borisovich Nikityuk ◽

Ksenia Valerievna Vibornaya ◽

...

Keyword(s):

Iron Deficiency ◽

Iron Metabolism ◽

Female Athletes ◽

Transferrin Saturation ◽

Daily Intake ◽

Food Product ◽

The Body ◽

Deficiency Anemia ◽

Ferritin Concentration ◽

Junior Athletes

The prevalence of iron deficiency in female athletes varies significantly, with 31% having a ferritin concentration below 12 ng/ml or a transferrin saturation of less than 16 ng/ml. The medical and biological substantiation of the composition was carried out and a specialized food product was developed for nutrition of female athletes of children and adolescents (12-17 years), that provides the intake an easily digestible of hem form’s iron and vitamins involved in iron metabolism in the body for at least 15 % and no more than 50% of the recommended daily intake.

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

Blood ◽

10.1182/blood.v118.21.5286.5286 ◽

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.

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ГЕПСИДИН, ТРАНСФЕРИН, ФЕРИТИН: ФІЗІОЛОГІЧНА РОЛЬ ЯК ЦЕНТРАЛЬНИХ РЕГУЛЯТОРІВ ОБМІНУ ЗАЛІЗА В ОРГАНІЗМІ

Science Review ◽

10.31435/rsglobal_sr/30122019/6862 ◽

2019 ◽

pp. 8-16

Author(s):

Станіслав Видиборець ◽

Дмитро Борисенко

Keyword(s):

Iron Deficiency ◽

Iron Metabolism ◽

Iron Homeostasis ◽

Physiological Role ◽

Clinical Importance ◽

Dynamic Parameter ◽

The Body ◽

Deficiency Anemia ◽

Laboratory Diagnostics ◽

The Given

The knowledge about mammalian iron metabolism has advanced dramatically over the past decades. Studies of genetics, biochemistry and molecular biology allowed us the identification and characterization of many of the molecules involved in regulation of iron homeostasis. Important progresses were made after the discovery in 2000 of a small peptide – hepsidin – that has been proved to play a central role in orchestration on iron metabolism also providing a link between iron metabolism and inflammation and innate immunity. Hepsidin directly interacts with ferroportin, the only known mammalian iron exporter, which is expressed by enterocytes, macrophages and hepatocytes. The direct hepsidin- ferroportin interaction allows an adaptative response from the body in situations that alter normal iron homeostasis (hypoxia, anemia, iron deficiency, iron overload, and inflammation). In clause the items of information on transport protein of iron - transferrin are stated. Its physiological role and clinical importance is shown. Dynamics of the contents of the hepsidin, transferrin, ferritin in persons with latent deficiency of iron. The conclusion about importance of the given parameter for laboratory diagnostics of iron deficiency condition is made. In the article the items of information about the ferritin - protein - depot of iron in body are given. Its physiological role and clinical importance is displayed. Dynamics of changes of the contents ferritin during treatment of the patients with iron deficiency anemia and persons with latent deficiency of iron is shown. The conclusion about the level of the ferritin in serum of blood is the important dynamic parameter for laboratory diagnostics iron deficiency of condition is made.

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Professional Female Athletes Are at a Heightened Risk of Iron-Deficient Erythropoiesis Compared With Nonathletes

International Journal of Sport Nutrition and Exercise Metabolism ◽

10.1123/ijsnem.2019-0193 ◽

2020 ◽

Vol 30 (1) ◽

pp. 48-53

Author(s):

Nenad Ponorac ◽

Mira Popović ◽

Dea Karaba-Jakovljević ◽

Zorislava Bajić ◽

Aaron Scanlan ◽

...

Keyword(s):

Iron Deficiency ◽

Female Athletes ◽

Iron Status ◽

Deficiency Anemia ◽

Training Volume ◽

Ferritin Concentration ◽

Weekly Training ◽

Iron Deficient ◽

Judo Athletes ◽

And Performance

This study primarily aimed to quantify and compare iron status in professional female athletes and nonathletes. Furthermore, this study also aimed to identify differences in iron status according to sporting discipline and explore the relationship between ferritin concentration and weekly training volume in professional athletes. A total of 152 participants were included in this study, including 85 athletes who were members of senior teams (handball, n = 24; volleyball, n = 36; soccer, n = 19; and judo, n = 6) involved at the highest level of competition and 67 nonathletes. A significantly greater proportion (p = .05) of athletes (27%) demonstrated iron-deficient erythropoiesis (IDE) compared with nonathletes (13%). There were nonsignificant differences (p > .05) in the prevalence of iron deficiency (ID; 49% vs. 46%) and iron deficiency anemia (IDA; 2% vs. 4%) between athletes and nonathletes. Similarly, the prevalence of ID, IDE, and IDA was not significantly different between sports (p > .05). Furthermore, training volume was negatively correlated with ferritin concentration in athletes (r: −.464, moderate, p < .001). Professional female athletes are at a heightened risk of IDE compared with nonathletes; therefore, they should be periodically screened for ID to reduce the deleterious effects on training and performance. The similar prevalence of ID, IDE, and IDA found across athletes competing in different sports suggests that overlaps exist between handball, volleyball, soccer, and judo athletes regarding risk of disturbance in iron metabolism.

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New findings on iron absorption conditioning factors

Revista Brasileira de Saúde Materno Infantil ◽

10.1590/s1519-38292004000300003 ◽

2004 ◽

Vol 4 (3) ◽

pp. 241-248 ◽

Cited By ~ 5

Author(s):

Rute Cândida Pereira ◽

Alcides da Silva Diniz ◽

Luiz Oscar Cardoso Ferreira

Keyword(s):

Iron Absorption ◽

The Body ◽

Vulnerable Groups ◽

Deficiency Anemia ◽

Public Health Issue ◽

Conditioning Factors ◽

Risk Increase ◽

New Findings ◽

Intake Regulation ◽

The Impact

The authors focus iron intake regulation in the body and the probable mechanisms related to iron absorption. They analyze the impact of iron absorption deficiency resulting in iron deficiency anemia, a public health issue of great impact in the world influencing child and maternal health risk increase. This paper aims at highlighting the problems affecting the uptake or inhibiting processes of iron absorption in an attempt to correlate information on conditioning factors and current findings. This study is a document based descriptive study comprising literature review. In food, iron has different forms, such as the heme and non-heme forms following different absorption pathways with different efficiency rates, depending on conditioning factors, such as diet profile, physiological aspects, iron chemical state, absorption regulation, transportation, storing, excretion and the presence of disease, They also discuss the current difficulties in dealing with iron nutritional deficiency in vulnerable groups, children and pregnant women, and focus data on iron consumption, adhesion to breast feeding and the frequency of prenatal care visits.

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Maturation, iron deficiency, and ligands in enteric radioiron transport in vitro

American Journal of Physiology-Legacy Content ◽

10.1152/ajplegacy.1963.204.1.171 ◽

1963 ◽

Vol 204 (1) ◽

pp. 171-175 ◽

Cited By ~ 14

Author(s):

W. S. Ruliffson ◽

J. M. Hopping

Keyword(s):

Ascorbic Acid ◽

Iron Deficiency ◽

Iron Absorption ◽

Deficiency Anemia ◽

Anaerobic Incubation ◽

Reverse Effect ◽

Factors Affecting ◽

Everted Gut Sac

The effects in rats, of age, iron-deficiency anemia, and ascorbic acid, citrate, fluoride, and ethylenediaminetetraacetate (EDTA) on enteric radioiron transport were studied in vitro by an everted gut-sac technique. Sacs from young animals transported more than those from older ones. Proximal jejunal sacs from anemic animals transported more than similar sacs from nonanemic rats, but the reverse effect appeared in sacs formed from proximal duodenum. When added to media containing ascorbic acid or citrate, fluoride depressed transport as did anaerobic incubation in the presence of ascorbic acid. Anaerobic incubation in the presence of EDTA appeared to permit elevated transport. Ascorbic acid, citrate, and EDTA all enhanced the level of Fe59 appearing in serosal media. These results appear to agree with previously established in vivo phenomena and tend to validate the in vitro method as one of promise for further studies of factors affecting iron absorption and of the mechanism of iron absorption.

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