Iron Status in Mice Carrying a Targeted Disruption of Lactoferrin

ABSTRACT Lactoferrin is a member of the transferrin family of iron-binding glycoproteins present in milk, mucosal secretions, and the secondary granules of neutrophils. While several physiological functions have been proposed for lactoferrin, including the regulation of intestinal iron uptake, the exact function of this protein in vivo remains to be established. To directly assess the physiological functions of lactoferrin, we have generated lactoferrin knockout (LFKO−/−) mice by homologous gene targeting. LFKO−/− mice are viable and fertile, develop normally, and display no overt abnormalities. A comparison of the iron status of suckling offspring from LFKO−/− intercrosses and from wild-type (WT) intercrosses showed that lactoferrin is not essential for iron delivery during the postnatal period. Further, analysis of adult mice on a basal or a high-iron diet revealed no differences in transferrin saturation or tissue iron stores between WT and LFKO−/− mice on either diet, although the serum iron levels were slightly elevated in LFKO-/- mice on the basal diet. Consistent with the relatively normal iron status, in situ hybridization analysis demonstrated that lactoferrin is not expressed in the postnatal or adult intestine. Collectively, these results support the conclusion that lactoferrin does not play a major role in the regulation of iron homeostasis.

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CBIO-10. REDUCED IRON EXPORT FUNCTIONS IN A CELL INTRINSIC MANNER TO DRIVE GLIOBLASTOMA GROWTH

Neuro-Oncology ◽

10.1093/neuonc/noaa215.070 ◽

2020 ◽

Vol 22 (Supplement_2) ◽

pp. ii17-ii17

Author(s):

Katie Troike ◽

Erin Mulkearns-Hubert ◽

Daniel Silver ◽

James Connor ◽

Justin Lathia

Keyword(s):

Tumor Cells ◽

Iron Uptake ◽

Iron Homeostasis ◽

Iron Status ◽

Tumor Grade ◽

Hfe Gene ◽

Iron Release ◽

Female Patients ◽

Cellular Iron

Abstract Glioblastoma (GBM), the most common primary malignant brain tumor in adults, is characterized by invasive growth and poor prognosis. Iron is a critical regulator of many cellular processes, and GBM tumor cells have been shown to modulate expression of iron-associated proteins to enhance iron uptake from the surrounding microenvironment, driving tumor initiation and growth. While iron uptake has been the central focus of previous investigations, additional mechanisms of iron regulation, such as compensatory iron efflux, have not been explored in the context of GBM. The hemochromatosis (HFE) gene encodes a transmembrane glycoprotein that aids in iron homeostasis by limiting cellular iron release, resulting in a sequestration phenotype. We find that HFE is upregulated in GBM tumors compared to non-tumor brain and that expression of HFE increases with tumor grade. Furthermore, HFE mRNA expression is associated with significantly reduced survival specifically in female patients with GBM. Based on these findings, we hypothesize that GBM tumor cells upregulate HFE expression to augment cellular iron loading and drive proliferation, ultimately leading to reduced survival of female patients. To test this hypothesis, we generated Hfe knockdown and overexpressing mouse glioma cell lines. We observed significant alterations in the expression of several iron handling genes with Hfe knockdown or overexpression, suggesting global disruption of iron homeostasis. Additionally, we show that knockdown of Hfe in these cells increases apoptosis and leads to a significant impairment of tumor growth in vivo. These findings support the hypothesis that Hfe is a critical regulator of cellular iron status and contributes to tumor aggression. Future work will include further exploration of the mechanisms that contribute to these phenotypes as well as interactions with the tumor microenvironment. Elucidating the mechanisms by which iron effulx contributes to GBM may inform the development of next-generation targeted therapies.

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Insights into Regulation and Function of the Major Stress-Induced hsp70 Molecular Chaperone In Vivo: Analysis of Mice with Targeted Gene Disruption of the hsp70.1 orhsp70.3 Gene

Molecular and Cellular Biology ◽

10.1128/mcb.21.24.8575-8591.2001 ◽

2001 ◽

Vol 21 (24) ◽

pp. 8575-8591 ◽

Cited By ~ 99

Author(s):

Lei Huang ◽

Nahid F. Mivechi ◽

Demetrius Moskophidis

Keyword(s):

Heat Stress ◽

Gene Family ◽

Synergistic Effects ◽

Single Gene ◽

Physiological Role ◽

Evolutionary Significance ◽

Homologous Gene ◽

Transcriptional Level ◽

Adult Mice

ABSTRACT The murine hsp70 gene family includes the evolutionarily conserved hsp70.1 andhsp70.3 genes, which are the major proteins induced by heat and other stress stimuli.hsp70.1 andhsp70.3 encode identical proteins which protect cells and facilitate their recovery from stress-induced damage. While the hsp70 gene family has been widely studied and the roles of the proteins it encodes as molecular chaperones in a range of human pathologies are appreciated, little is known about the developmental regulation of hsp70.1 andhsp70.3 expression and the in vivo biological function of their products. To directly study the physiological role of these proteins in vivo, we have generated mice deficient in heat shock protein 70 (hsp70) by replacing thehsp70.1 orhsp70.3 gene with an in-frame β-galactosidase sequence. We report here that the expression ofhsp70.1 andhsp70.3 is developmentally regulated at the transcriptional level, and an overlapping expression pattern for both genes is observed during embryo development and in the tissues of adult mice. hsp70.1 −/− orhsp70.3 −/− mice are viable and fertile, with no obvious morphological abnormalities. In late embryonic stage and adult mice, both genes are expressed constitutively in tissues exposed directly to the environment (the epidermis and cornea) and in certain internal organs (the epithelium of the tongue, esophagus, and forestomach, and the kidney, bladder, and hippocampus). Exposure of mice to thermal stress results in the rapid induction and expression of hsp70, especially in organs not constitutively expressing hsp70 (the liver, pancreas, heart, lung, adrenal cortex, and intestine). Despite functional compensation in the single-gene-deficient mice by the intact homologous gene (i.e.,hsp70.3 inhsp70.1 −/− mice and vice versa), a marked reduction in hsp70 protein expression was observed in tissues under both normal and heat stress conditions. At the cellular level, inactivation of hsp70.1 orhsp70.3 resulted in deficient maintenance of acquired thermotolerance and increased sensitivity to heat stress-induced apoptosis. The additive or synergistic effects exhibited by coexpression of both hsp70 genes, and the evolutionary significance of the presence of both hsp70genes, is hence underlined.

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Serum Prohepcidin and Iron Homeostasis in Patients with Breast Cancer

Blood ◽

10.1182/blood.v118.21.5291.5291 ◽

2011 ◽

Vol 118 (21) ◽

pp. 5291-5291

Author(s):

Janet G. Grudeva ◽

Ivanka Slavejnova Nenova ◽

Dora Dimitrova Terzieva ◽

Maria Ivanova Spasova ◽

Nikolay Petrov Boyadjiev

Keyword(s):

Breast Cancer ◽

Iron Homeostasis ◽

Conflicts Of Interest ◽

Iron Status ◽

Transferrin Saturation ◽

University Hospital ◽

Direct Result ◽

Full Blood Count ◽

Normocytic Anemia ◽

Cytotoxic Treatment

Abstract Abstract 5291 Introduction: Cancer-related anemia (CRA) has multifactorial etiology and complex pathogenesis. It is defined as normochromic, normocytic anemia with reticulocyto-penia and hypoferremia. Hepcidin is recognized as the central factor in causing CRA. Objective: To investigate the changes in the serum levels of prohepcidin (pHp) and markers of iron homeostasis for gathering more data on the pathogenesis of CRA. Patients and Methods: The authors analyzed prospectively 46 newly diagnosed women with breast cancer, aged 29–72 years (average 47.5±9.0 SD), who had the same clinical stage, histology and hormonal status. They were diagnosed and treated in the Clinic of Oncology and Hematology - University Hospital for a 2-year period (2009–2010). Serum pHp levels and common markers of iron status including serum iron (sFe), transferrin saturation, soluble tranferrin receptor (sTfR), Zn-protoporphyrin (ZPP), ferritin as well as vitamin B12 and folate were measured before treatment initiation and two months afterwards. Serum pHp was determined by a competitive immunotest. All statistical data was computed by the methods of variational and correlation analyses. Results and Discussion: For the two-month follow up interval parameters of full blood count remained without statistically significant deviation. Although the analyzed parameters in the first and second blood samples remained within the reference intervals, the decrease of pHp and the changes of iron-containing substances and ZPP in red blood cells cannot be neglected. However the correlation coefficient (R) between decreased pHp, increased sFe (R=0.314), sTfR (R=0.258), ZPP (R=0.118) and decreased ferritin (R=0.099), were low instead of the expected higher relationship. The obtained results do not support the idea that iron increase and other changes of iron homeostasis in these patients is a direct result of regulatory decrease of pHp. The two-month interval is likely short enough to rule out a potential direct suppressive effect of the specific cytotoxic treatment, and therefore we do not discuss such potential influence on iron homeostasis. Conclusion: Iron homeostasis dysregulation is one of CRA components. In its complex pathogenesis several other factors interfere e.g. such related to the disease; therapy related factors; altered erythropoietin production; activation of cytokines (IL-6 is the major promoter of hepcidin production). Disclosures: No relevant conflicts of interest to declare.

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Ndfip1-deficient mice have impaired DMT1 regulation and iron homeostasis

Blood ◽

10.1182/blood-2010-07-295287 ◽

2011 ◽

Vol 117 (2) ◽

pp. 638-646 ◽

Cited By ~ 35

Author(s):

Natalie J. Foot ◽

Yew Ann Leong ◽

Loretta E. Dorstyn ◽

Hazel E. Dalton ◽

Kristen Ho ◽

...

Keyword(s):

Metal Ion ◽

Iron Homeostasis ◽

Transferrin Saturation ◽

Hypochromic Anemia ◽

Adaptor Proteins ◽

Normal Diet ◽

Immunodeficient Mice ◽

In The Wild

Abstract The divalent metal ion transporter DMT1 is critical for nonheme iron import. We have previously shown that DMT1 is regulated in vitro by ubiquitination that is facilitated by the adaptor proteins Ndfip1 and Ndfip2. Here we report that in Ndfip1−/− mice fed a low- iron diet, DMT1 expression and activity in duodenal enterocytes are significant higher than in the wild-type animals. This correlates with an increase in serum iron levels and transferrin saturation. Liver and spleen iron stores were also increased in Ndfip1−/− mice fed a normal diet. Counterintuitive to the increase in iron uptake, Ndfip1−/− mice fed a low iron diet develop severe microcytic, hypochromic anemia. We demonstrate that this is due to a combination of iron deficiency and inflammatory disease in Ndfip1−/− mice, because Ndfip1−/−/Rag1−/− immunodeficient mice fed a low iron diet did not develop anemia and showed an iron overload phenotype. These data demonstrate that Ndfip1 is a critical mediator of DMT1 regulation in vivo, particularly under iron restricted conditions.

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Regulatory Mechanisms for Iron Homeostasis Are Present in Small Preterm Newborns

Blood ◽

10.1182/blood.v128.22.2460.2460 ◽

2016 ◽

Vol 128 (22) ◽

pp. 2460-2460

Author(s):

Carina Levin ◽

Marina Marina Peniakov ◽

Dan Reich ◽

Scott Weiner ◽

Jamal Hasnein ◽

...

Keyword(s):

Birth Weight ◽

Blood Transfusion ◽

Preterm Infants ◽

Iron Supplementation ◽

Iron Homeostasis ◽

Reticulocyte Count ◽

Iron Status ◽

Transferrin Saturation ◽

Regulatory Mechanisms ◽

Vlbw Infants

Abstract Iron, an essential micronutrient, plays an important role in cellular functions. To prevent deficiency, iron supplementation is universally recommended for preterm infants; nevertheless, assessment of newborn iron stores is not currently recommended. Both iron deficiency and iron excess early in life can have adverse effects on neurodevelopment and outcomes, and therefore sensitive and specific methods for evaluating iron status and determining optimal iron supplementation are essential. The current study aimed to evaluate iron status and iron-supplementation efficacy/toxicity in preterm infants using new laboratory methods, and to correlate iron status with clinical, nutritional, laboratory and therapeutic factors, and the amount of blood extracted and transfused. We evaluated 50 very low birth weight (VLBW) preterm infants treated under standard protocols at the Emek Medical Center NICU, 26 (54%) male. Iron supplementation was administered enterally from 4 wk of age (4 mg elemental iron/kg body weight daily). Laboratory studies included CBC, reticulocyte count, reticulocyte hemoglobin (Hb) content, iron, transferrin, transferrin saturation, ferritin, erythropoietin, hepcidin, CRP and non-transferrin-bound iron (NTBI) (Aferrix, Israel). Samples were obtained at 3 different times during hospitalization: (-0) before starting oral iron supplementation, (-1) on d 4-7 of supplementation, and (-2) after at least 2 wk of supplementation. To better understand iron metabolism, the analyzed preterm population was divided into subgroups for comparison: infants who did not require blood transfusion (No-BT) vs. those who received one or more transfusions (BT); infants who did not show abnormal NTBI levels (≤0.19 μmol/L; No-NTBI) vs. those with abnormal NTBI levels (≥ 0.2 μmol/L in one or more samples; NTBI). Mean birth weight of the studied infants was 1264.5 ± 342 g, gestational age 29.1 ± 2.5 wk, age at hospital discharge 57.6 ± 20 d and weight at discharge, 2412 ± 421 g. The BT group included 35 (70%) infants. The mean birth weight was lower in the BT vs. No-BT group (1199 ± 351 g vs. 1416±273 g, P = 0.04). Mean red blood cell, Hb, and hematocrit were higher in the BT vs. No-BT group. Conversely, mean platelet count, reticulocyte count, and erythropoietin were higher in the No-BT vs. BT group, suggesting an erythropoietic response to lower Hb levels and utilization of iron through effective erythropoiesis. In the BT group, mean serum iron, ferritin, transferrin saturation and hepcidin were higher, whereas transferrin was lower than in the No-BT group. This reflects increased iron burden induced by the transfusions, making NTBI more likely to develop with potential toxicity. Regarding NTBI, 34 (68%) of the infants were in the No-NTBI group, and 16 (32%) showed increased NTBI levels. The Δiron (sum of iron from diet, supplementation and transfusion minus iron output via blood extractions) before starting supplementation was significantly higher in the NTBI vs. No-NTBI group. Mean transferrin saturation at -0 was higher, whereas transferrin at -2 was lower in the NTBI vs. No-NTBI group, demonstrating a higher iron burden in NTBI infants. The odds of developing NTBI rose 7.2% for each percent increment in transferrin saturation at -0 (O.R. 1.072, 95% CI, 1.005-1.143, P = 0.036), and a cutoff of 26% at -0 gave 80% sensitivity and 41% specificity for the presence of NTBI (AUC 0.68). Thus VLBW infants show evidence of regulatory mechanisms for iron homeostasis and iron utilization for erythropoiesis; however, the protective responses are not developed enough to limit the appearance of circulating free iron with potential toxic effects. Neither adverse effects nor presence of NTBI were associated with enteral iron supplementation. Premature infants who received blood transfusions had a positive iron balance, higher Hb and ferritin levels, and reduced erythropoiesis. Consequently, these babies are more likely to develop free iron. Conventional biomarkers are effective for evaluating iron status in VLBW infants. Transferrin saturation seems to be the most reliable and "physiological" biomarker, and a potential predictor of abnormal NTBI levels. These findings support an individualized approach to iron supplementation based on the characteristics of the specific preterm infant while taking into consideration past need for blood transfusion and the infant's iron status. Disclosures No relevant conflicts of interest to declare.

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Expression of hepcidin in hereditary hemochromatosis: evidence for a regulation in response to the serum transferrin saturation and to non-transferrin-bound iron

Blood ◽

10.1182/blood-2002-11-3610 ◽

2003 ◽

Vol 102 (1) ◽

pp. 371-376 ◽

Cited By ~ 167

Author(s):

Sven G. Gehrke ◽

Hasan Kulaksiz ◽

Thomas Herrmann ◽

Hans-Dieter Riedel ◽

Karin Bents ◽

...

Keyword(s):

Iron Overload ◽

Serum Ferritin ◽

Iron Homeostasis ◽

Iron Status ◽

Hereditary Hemochromatosis ◽

Transferrin Saturation ◽

Serum Transferrin ◽

Transcript Levels ◽

Hepcidin Expression

Abstract Experimental data suggest the antimicrobial peptide hepcidin as a central regulator in iron homeostasis. In this study, we characterized the expression of human hepcidin in experimental and clinical iron overload conditions, including hereditary hemochromatosis. Using quantitative reverse transcriptase-polymerase chain reaction (RT-PCR), we determined expression of hepcidin and the most relevant iron-related genes in liver biopsies from patients with hemochromatosis and iron-stain-negative control subjects. Regulation of hepcidin mRNA expression in response to transferrin-bound iron, non-transferrin-bound iron, and deferoxamine was analyzed in HepG2 cells. Hepcidin expression correlated significantly with serum ferritin levels in controls, whereas no significant up-regulation was observed in patients with hemochromatosis despite iron-overload conditions and high serum ferritin levels. However, patients with hemochromatosis showed an inverse correlation between hepcidin transcript levels and the serum transferrin saturation. Moreover, we found a significant correlation between hepatic transcript levels of hepcidin and transferrin receptor-2 irrespective of the iron status. In vitro data indicated that hepcidin expression is down-regulated in response to non-transferrin-bound iron. In conclusion, the presented data suggest a close relationship between the transferrin saturation and hepatic hepcidin expression in hereditary hemochromatosis. Although the causality is not yet clear, this interaction might result from a down-regulation of hepcidin expression in response to significant levels of non-transferrin-bound iron. (Blood. 2003;102:371-376)

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Interrelationships between circulating gastrin and iron status in mice and humans

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.90359.2008 ◽

2008 ◽

Vol 295 (4) ◽

pp. G855-G861 ◽

Cited By ~ 9

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.

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Deferoxamine inhibition of malaria is independent of host iron status.

Journal of Experimental Medicine ◽

10.1084/jem.168.1.375 ◽

1988 ◽

Vol 168 (1) ◽

pp. 375-387 ◽

Cited By ~ 81

Author(s):

C Hershko ◽

T E Peto

Keyword(s):

Iron Status ◽

Transferrin Saturation ◽

Direct Interaction ◽

Intracellular Iron ◽

Intact Cells ◽

Labile Iron Pool ◽

Peak Parasitemia ◽

Labile Iron ◽

Iron Pool

The mechanism whereby deferoxamine (DF) inhibits the growth of malaria parasites was studied in rats infected with Plasmodium berghei. Peak parasitemia was 32.6% (day 14) in untreated controls and 0.15% (day 7) in rats receiving 0.33 mg/g in 8 hourly DF injections, subcutaneously. DF inhibition of parasite growth was achieved without any reduction in transferrin saturation or hemoglobin synthesis and with only a partial (56%) depletion of hepatic iron stores. Dietary iron depletion resulted in anemia (hematocrit 25 vs. 46%), microcytosis (MCV 54 vs. 60 fl), and reduced transferrin saturation (17 vs. 96%) without any effect on infection (peak parasitemia 30 vs. 36%). Similarly, parenteral iron loading with ferric citrate over 10 d (75 mg iron/kg) failed to aggravate infection. In a search for evidence of direct interaction between DF and parasitized erythrocytes, gel filtration and ultrafiltration was performed on hemolysates obtained from in vivo 59Fe-labeled parasitized erythrocytes. This showed that 1.1-1.9% of the intracellular radioiron was located in a chelatable, labile iron pool. Incubation of intact cells with 0-500 microM DF resulted in a proportional increase in intracellular iron chelation, and the chelation of all available labile intracellular iron was completed within 6 h. These observations indicate that the severity of P. berghei infection in rats and its in vivo suppression by DF are independent of host iron status and suggest that DF inhibition of malaria involves intracellular chelation of a labile iron pool in parasitized erythrocytes.

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ANALYSIS OF RET-HE IN CHRONIC KIDNEY DISEASE PATIENTS AT DR.WAHIDIN SUDIROHUSODO HOSPITAL, MAKASSAR

INDONESIAN JOURNAL OF CLINICAL PATHOLOGY AND MEDICAL LABORATORY ◽

10.24293/ijcpml.v25i1.1481 ◽

2019 ◽

Vol 25 (1) ◽

pp. 7

Author(s):

Febrina Rovani ◽

Asvin Nurulita ◽

Mansyur Arif

Keyword(s):

Chronic Kidney Disease ◽

Kidney Disease ◽

Iron Homeostasis ◽

Complete Blood Count ◽

Binding Capacity ◽

Iron Status ◽

Transferrin Saturation ◽

Test Method ◽

Pathology Laboratory ◽

Significant Difference

Anemia, the common feature of Chronic Kidney Disease (CKD), is a multifactorial process due to disordered erythropoiesis and iron homeostasis. Determining the cause of anemia is important for adequate management. A bone marrow biopsy using Prussian Blue as the gold standard for diagnosis is invasive and more complicated to perform. Reticulocytes-Hemoglobin (Ret-He) a new parameter that indicates the hemoglobin content in reticulocytes is faster, easier, and less expensive. This study aimed to analyze the Ret-He in determining the iron status in patients with CKD. A cross-sectional study was held in the Clinical Pathology Laboratory of Dr. Wahidin Sudirohusodo Hospital Makassar during April-August 2016. Forty-five (45) samples were tested for iron serum (Fe), Total Iron Binding Capacity (TIBC), and Complete Blood Count (CBC) ordered by the physician. Reticulocytes-Hemoglobin was tested using the whole blood. Subjects were around the age of 19-71 years, no significant difference was found between numbers of males and females (46.6% and 53.3%). Hemoglobin median was 8 (5.0-15) g/dL, Fe 50 (6-177) U/mL, TIBC 183 (73-379), Transferrin Saturation (Tsat) 25 (5-95)%. Spearman correlation test method showed significant correlations between Ret-He and iron serum r=0.533, p <0.001, Ret-He and TIBC r=0.321 p=0.031 Ret-He and transferrin saturation r=0.416 p=0.019. The Mann-Whitney method showed no significant difference of Ret-He in both groups (Tsat <20% and >20%). There were significant correlations between Ret-He and iron, Ret-He and TIBC, Ret-He and transferrin saturation. A further study using larger samples is suggested to consider factors affecting the result of Ret-He.

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The Association between Hepcidin and Iron Status in Children and Adolescents with Obesity

Journal of Nutrition and Metabolism ◽

10.1155/2021/9944035 ◽

2021 ◽

Vol 2021 ◽

pp. 1-7

Author(s):

Ekkarit Panichsillaphakit ◽

Orapa Suteerojntrakool ◽

Chitsanu Pancharoen ◽

Issarang Nuchprayoon ◽

Sirinuch Chomtho

Keyword(s):

Iron Deficiency ◽

Iron Homeostasis ◽

Complete Blood Count ◽

Iron Status ◽

Standard Deviation Score ◽

Transferrin Saturation ◽

Obese Group ◽

Control Group ◽

Low Grade ◽

Serum Hepcidin

Introduction. Iron deficiency (ID) is the most common nutritional deficiency found in pediatric practice. A higher prevalence of ID may be found in children with obesity. Obesity is a chronic low-grade inflammatory condition. It is postulated that inflammation increases hepcidin, a regulator of iron homeostasis. The aim of this study was to investigate the associations between iron status, hepcidin, and BMI-standard deviation score (BMI-SDS) in children with and without obesity. Methods. A cross-sectional study of Thai children with obesity (5 to 15 years old) versus age- and sex-matched, nonobese controls was conducted. A total of 63 children with obesity and 27 controls were enrolled. Complete blood count, serum iron, ferritin, transferrin saturation, and total iron binding capacity were analyzed. Serum hepcidin-25 was assayed using a hepcidin ELISA Kit (Human Hepc25). Results. There were 63 children with obesity, the median age (IQR) being 10 (9–13) years, and 27 controls. The median (IQR) BMI-SDS of the obese group was 2.3 (2.0–2.6) vs. −0.5 ((−1.3)−0.4) of the control group. ID was diagnosed in 27 children in the obese group (42.9%); 4 of the children with obesity and ID had anemia. Serum hepcidin-25 levels of the children with ID vs. without ID in the obese group were not significantly different (median (IQR) 25 (12.9–49.2) and 26.4 (12.6–43.6), respectively) but both of them were significantly higher than controls (19.7 (8.3–25.5) ng/ml, p = 0.04). BMI-SDS was positively correlated with hepcidin-25 (r = 0.28, p = 0.001). Conclusion. Prevalence of iron deficiency in Thai children with obesity and serum hepcidin-25 was higher than controls. Further study in a larger population, preferably with interventions such as weight loss program, is warranted to clarify this association.

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