|Year : 2020 | Volume
| Issue : 1 | Page : 30-33
The significance of serum hepcidin on iron status in overweight and obese patients with iron-deficiency anemia
Abeer Anwer Ahmed
Department of Pathology, Faculty of Medicine, University of Mustansiriyah, Baghdad, Iraq
|Date of Submission||23-Nov-2019|
|Date of Acceptance||25-Dec-2019|
|Date of Web Publication||15-Apr-2020|
Dr. Abeer Anwer Ahmed
Department of Pathology, Faculty of Medicine, University of Mustansiriyah, Baghdad
Source of Support: None, Conflict of Interest: None
BACKGROUND: Deficiency of iron is one of the most prevalent nutritional disorders, and obesity is an increasing nutritional problem, but only a few studies mention a possible association between them in Iraq. Adipocytes secrete adipokines, some of them are related to the inflammatory response in addition to hepcidin, a hormone that mediates iron metabolism.
OBJECTIVES: This study aimed to assess the significance of serum hepcidin in obese patients with iron deficiency.
PATIENTS MATERIALS AND METHODS: Ninty patients were separated into Group 1 (normal weight), Group 2 (30 overweight), and the Group 3 (30 obese). All patients were investigated by complete blood count, serum hepcidin, iron, total iron-binding capacity, and ferritin using the standard laboratory techniques.
RESULTS: There were no significant differences among the groups regarding the severity of anemia, red cell indices, white blood cells, and platelets count. The obese group had significantly higher serum hepcidin and ferritin (P = 0.003, 0.040, respectively), while serum iron is lower. Serum hepcidin positively correlated with the serum ferritin but inversely correlated with serum iron. Increased hepcidin level in obesity could be related to inflammatory adipokines that effect on hepatic hepcidin transcription and hepcidin mRNA expression, in addition to the nonhepatic production of hepcidin in an autocrine manner; hepcidin, in turn, is responsible for low serum iron, but a high ferritin level in correlation to high hepcidin may explain by low-grade chronic inflammation associated with obesity.
CONCLUSIONS: The severity of iron-deficiency anemia is not affected by body weight; however, significantly higher serum hepcidin and ferritin in the obese patient with a lower serum iron should be considered during the assessment of iron status in those patients.
Keywords: Ferritin, hepcidin, iron deficiency, obese
|How to cite this article:|
Ahmed AA. The significance of serum hepcidin on iron status in overweight and obese patients with iron-deficiency anemia. Iraqi J Hematol 2020;9:30-3
|How to cite this URL:|
Ahmed AA. The significance of serum hepcidin on iron status in overweight and obese patients with iron-deficiency anemia. Iraqi J Hematol [serial online] 2020 [cited 2020 Jul 13];9:30-3. Available from: http://www.ijhonline.org/text.asp?2020/9/1/30/282519
| Introduction|| |
Globally, the most common disorder of nutrition is anemia due to the lack of iron, about 1.6–2 billion people are anemic and 30%–50% of them are iron-deficiency anemia (IDA)., On the other hand, about 13% of the world's adults are obese and 39% are overweight, and between 1980 and 2014, there was an increase in the prevalence of obesity more than twice. In spite of that, only a few studies mention a possible association between IDA and obesity.
Iron deficiency is the first cause of anemia worldwide, particularly in developing countries caused by inadequate iron intake and blood loss. The red cells in IDA are hypochromic microcytic with low mean corpuscular hemoglobin and mean corpuscular volume and low serum iron, serum ferritin, and serum hepcidin but high total iron-binding capacity (TIBC). Bone marrow iron stores and erythroblast iron are diminished.
Overweight and obesity
Overweight and obesity can be defined as increased fat accumulation which may cause health impairment. Body mass index (BMI) is a simple index which is used for the classification of obesity and overweight in adults by dividing weight in kilograms by the square of the height in meters (kg/m2). The WHO defines those whose BMI ≥25 as overweight, while obesity refers to persons who have BMI ≥30.
Recently, an association is thought to be present between obesity and chronic inflammation because adipocytes secrete about 50 proteins (adipokines), some of them are related to the inflammatory response, such as “tumor necrosis factor-α, adiponectin, interleukin-1 β, interleukin–10, interleukin-6, interleukin-8, haptoglobin, vascular endothelial growth factor, nerve growth factor, macrophage migration inhibitory factor, monocyte chemoattractant protein-1, and plasminogen activator inhibitor-1.”
Is a hormone synthesized principally by the cells of the liver and is secreted in the plasma then excreted in the urine, it is also synthesized by adipose tissue, with an increased expression of hepcidin messenger RNA in adipose tissue of the obese person.
Hepcidin regulates the absorption of iron and the release of iron from macrophages; it also mediates innate immunity and regarded as Type II acute-phase protein.
The production of hepcidin is regulated by many mechanisms which include an inflammation-related mechanism “via interleukin-6, interleukin-1, interferon-gamma, and tumor necrosis factor alpha” and by iron status and erythropoietic activity-related mechanism., Therefore, the study aimed to evaluate the serum hepcidin level in normal weight, overweight, and obese Patients with IDA and to find if there is a significant correlation with iron status (serum iron and serum ferritin).
| Patients and Methods|| |
This study was conducted on 90 patients selected according to the results of complete blood count (CBC), blood film, and iron profile study including serum iron, TIBC, and serum ferritin.
Patients with IDA were arranged into three groups: Group 1 included 30 normal weight patients, Group 2 included 30 overweight patients, and Group 3 included 30 obese patients.
The study included adult patients with newly diagnosed IDA of both the genders.
Pregnant women; individuals with recent blood transfusion or donation in the previous 3 months; individuals with iron supplement intake within the previous 3 months; and patients with malignant diseases, chronic inflammatory diseases, acute and chronic infections, and liver and renal diseases were excluded from this study, after good history taking, physical examination, and review of laboratory investigations including CBC, blood film, erythrocyte sedimentation rate (ESR), C-reactive protein, and liver and renal function test.
This study was approved by review ethical committee of Iraqi council for medical specializations. It was conducted on patients with IDA, in accordance with the ethical standards and after obtaining informed consent from the participants.
Eight milliliters (ml) of peripheral blood were withdrawn by aseptic technique, each sample was divided into two tubes, first 4 ml in K3 EDTA-coated tube for CBC, blood film, and ESR tests and the second 4 ml in gel and activator tubes to obtain sera.
The following laboratory investigations were applied to all patients:
- CBC using (Sysmex KX-21N, Japan) hematology autoanalyzer and blood film and ESR were done manually
- The direct colorimetric assay was used to measure serum iron and TIBC using a spectrophotometer (UK, Cecil CE1011) and using the commercial kit from Human Diagnostics worldwide,
- Serum ferritin was measured using automated immunoanalyzer (mini Vidas, France, bioMérieux) enzyme immunoassay and the commercial kit (France, bioMerieux, Ferritin, VIDAS, 30 411)
- Serum Hepcidin was estimated by enzyme-linked immunosorbent assay (ELISA) which use standard enzyme reader from Diagnostic Automation Inc., USA (ELISA Reader), using a commercial kit (Human Hepcidin kit ELISA, CUSABIO, CSB-E14239h, China).
Statistical Package for the social sciences, IBM SPSS Statistics 184.108.40.206 was applied for the data analysis. Using the test of one-way analysis of variance, the significant differences among studied groups were assessed. The correlation between the variables was considered statistically significant if P < 0.05.
| Results|| |
In normal weight group of patients, the mean age was 28 ± 8 years, while in overweight and obese groups, it was 22 ± 6 and 40 ± 8 years, respectively, with a significant difference among these groups (P = 0.041) indicating that obesity is more among older age patients. There was a slightly higher female-to-male ratio in all the three groups of patients, with no significant differences among them.
The differences were insignificant among the groups regarding the severity of anemia, red cell indices, white blood cells, and platelets count.
Serum hepcidin levels were significantly higher in the obese patients (Group 3), while serum ferritin was low in Group 1 and 2, whereas in Group 3, the value of serum ferritin varied between low and normal level and was significantly higher in the obese Group 3, while serum iron is lower, as seen in [Table 1].
|Table 1: Descriptive parameters in three groups of patients with iron-deficiency anemia|
Click here to view
The main cause of IDA was chronic blood loss in 65% of the patients, while other causes such as increased demands and poor iron intake or malabsorption form 35% of causes.
Serum hepcidin correlated positively with serum ferritin (r = 0.82, P < 0.003) but negatively correlated with serum iron (r = −0.37, P = 0.043) in Group 3 patients.
| Discussion|| |
Increased hepcidin level in obesity was mentioned in other studies conducted on children and women with obesity who had significantly higher serum hepcidin levels in comparison to persons whose weight was normal, and this may be a cause that inhibits absorption of dietary iron in patients with obesity.,,
The higher serum hepcidin level could be related to inflammatory adipokines (particularly interleukin-6 and adipokine leptin that have common biological features with interleukin-6) that affect on hepatic hepcidin transcription and hepcidin mRNA expression via the JAK-STAT three pathway, in addition to the inflammatory-induced nonhepatic production of hepcidin in an autocrine manner.,,,
Hepcidin, in turn, is responsible for low serum iron by decreasing the absorption of iron from the intestinal mucosa and by raising the rate of sequestration of iron in macrophages, but a high ferritin level in correlation to high hepcidin has not yet been explained; however, low-grade chronic inflammation associated with obesity could be responsible for higher serum ferritin; similarly, other studies mention high serum ferritin in those with severe adiposity and consider it an acute-phase reactant that is elevated even if true iron deficiency is present, and its production is induced by many inflammatory cytokines.,,
On the other hand, Fleming and Sly mention a similar elevation in hepcidin levels that correlate with serum ferritin and they thought that the increased ferritin levels cause increase in the secretion of hepcidin by mechanisms which are unknown, leading to lowering in the absorption of iron from the intestine, and propose that there may be an additional unknown factor which can affect both ferritin and hepcidin levels as a response to iron state and inflammatory process. Similar changes in serum iron markers that are typical of chronic inflammation but are not actually associated with “anemia of inflammation” are also mentioned by a population-based study by Ausk and Ioannou.
| Conclusions|| |
Significantly higher serum hepcidin and ferritin in overweight and obese patients with a lower serum iron should be considered while assessing the status of iron in those patients. Further studies are recommended to evaluate hepcidin and the inflammatory adipokines associated with obesity in anemia of chronic diseases and IDA.
The authors would like to the University of Mustansiriyah/Faculty of medicine, particularly the department of pathology and forensic medicine, and all the laboratory staff.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
McLean E, Cogswell M, Egli I, Wojdyla D, de Benoist B. Worldwide prevalence of anaemia, WHO Vitamin and Mineral Nutrition Information System, 1993-2005. Public Health Nutr 2009;12:444-54.
Stoltzfus RJ. Iron deficiency: Global prevalence and consequences. Food Nutr Bull 2003;24:S99-103.
Cepeda-Lopez AC, Allende-Labastida J, Melse-Boonstra A, Osendarp SJ, Herter-Aeberli I, Moretti D, et al
. The effects of fat loss after bariatric surgery on inflammation, serum hepcidin, and iron absorption: A prospective 6-mo iron stable isotope study. Am J Clin Nutr 2016;104:1030-8.
Datz C, Felder TK, Niederseer D, Aigner E. Iron homeostasis in the metabolic syndrome. Eur J Clin Invest 2013;43:215-24.
Aigner E, Feldman A, Datz C. Obesity as an emerging risk factor for iron deficiency. Nutrients 2014;6:3587-600.
Trayhurn P. Endocrine and signalling role of adipose tissue: New perspectives on fat. Acta Physiol Scand 2005;184:285-93.
Bekri S, Gual P, Anty R, Luciani N, Dahman M, Ramesh B, et al
. Increased adipose tissue expression of hepcidin in severe obesity is independent from diabetes and NASH. Gastroenterology 2006;131:788-96.
Weinstein DA, Roy CN, Fleming MD, Loda MF, Wolfsdorf JI, Andrews NC. Inappropriate expression of hepcidin is associated with iron refractory anemia: Implications for the anemia of chronic disease. Blood 2002;100:3776-81.
Babitt JL, Huang FW, Wrighting DM, Xia Y, Sidis Y, Samad TA, et al
. Bone morphogenetic protein signaling by hemojuvelin regulates hepcidin expression. Nat Genet 2006;38:531-9.
Weizer-Stern O, Adamsky K, Amariglio N, Levin C, Koren A, Breuer W, et al
. Downregulation of hepcidin and haemojuvelin expression in the hepatocyte cell-line HepG2 induced by thalassaemic sera. Br J Haematol 2006;135:129-38.
Aeberli I, Hurrell RF, Zimmermann MB. Overweight children have higher circulating hepcidin concentrations and lower iron status but have dietary iron intakes and bioavailability comparable with normal weight children. Int J Obes (Lond) 2009;33:1111-7.
del Giudice EM, Santoro N, Amato A, Brienza C, Calabrò P, Wiegerinck ET, et al
. Hepcidin in obese children as a potential mediator of the association between obesity and iron deficiency. J Clin Endocrinol Metab 2009;94:5102-7.
Tussing-Humphreys LM, Nemeth E, Fantuzzi G, Freels S, Guzman G, Holterman AX, et al
. Elevated systemic hepcidin and iron depletion in obese premenopausal females. Obesity (Silver Spring) 2010;18:1449-56.
Vuppalanchi R, Troutt JS, Konrad RJ, Ghabril M, Saxena R, Bell LN, et al
. Serum hepcidin levels are associated with obesity but not liver disease. Obesity (Silver Spring) 2014;22:836-41.
Chung B, Matak P, McKie AT, Sharp P. Leptin increases the expression of the iron regulatory hormone hepcidin in HuH7 human hepatoma cells. J Nutr 2007;137:2366-70.
Wang CY, Babitt JL. Hepcidin regulation in the anemia of inflammation. Curr Opin Hematol 2016;23:189-97.
Ganz T. Hepcidin, a key regulator of iron metabolism and mediator of anemia of inflammation. Blood 2003;102:783-8.
Fleming RE, Sly WS. Hepcidin: A putative iron-regulatory hormone relevant to hereditary hemochromatosis and the anemia of chronic disease. Proc Natl Acad Sci U S A 2001;98:8160-2.
Tijerina-Sáenz A, Martínez-Garza NE, Ramírez-López E, Solís-Pérez E, Martínez-Báez AZ. Iron status and dietary intakes of iron in normal-weight and obese young Mexican women. Nutr Hosp 2015;31:2412-8.
Greenberg AS, Obin MS. Obesity and the role of adipose tissue in inflammation and metabolism. Am J Clin Nutr 2006;83:461S-5S.
Fitzsimons EJ, Brock JH. The anaemia of chronic disease. BMJ 2001;322:811-2.
Ausk KJ, Ioannou GN. Is obesity associated with anemia of chronic disease? A population-based study. Obesity (Silver Spring) 2008;16:2356-61.