Iron absorption in dysmetabolic iron overload syndrome is decreased and correlates with increased plasma hepcidin
Abstract
Background/aims The dysmetabolic iron overload syndrome (DIOS) is a common disorder but its origin remains unclear.Methods A case-control study was conducted to compare intestinal absorption of iron in 16 men with DIOS (age 53 +/- 11 years, serum ferritin 750 +/- 372 microg/l, hepatic iron 78 +/- 25 micromol/g) and in 32 age-matched controls with normal body iron stores (16 overweight subjects and 16 lean subjects). Intestinal absorption was calculated as the area under the curve (AUC) of 58Fe administered orally and correlated with plasma hepcidin and with insulin resistance parameters including HOMA.Results Intestinal iron absorption was lower in DIOS (AUC = 22.4 +/- 15.9 microg/l/h) compared to both overweight controls (AUC = 40.5 +/- 29.4 microg/l/h, p=0.04) and to lean controls (AUC = 102.5 +/- 113.5 microg/l/h, p < 0.01). There was an inverse correlation between intestinal iron absorption and plasma hepcidin (r = -0.61, p < 0.001), HOMA (r = -0.35, p = 0.01) and C reactive protein (r = -0.52, p < 0.001).Conclusions In overweight subjects with normal iron stores, iron absorption is decreased through hepcidin upregulation. In patients with DIOS, this decrease is more pronounced due to an additional effect of iron excess on circulating hepcidin levels.
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Obesity-related iron deficiency and DIOS represent different manifestations of the same underlying pathophysiological process.
“As decreased enteral iron absorption and elevated hepcidin expression are found in both obesity-related iron deficiency and DIOS, we suggest that these conditions represent different manifestations of the same underlying pathophysiological process [67,73].”
From Obesity as an emerging risk factor for iron deficiency (2014) · cites this paper as [73]
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“Results from more recent studies demonstrated (Ruivard et al. 2009, Tsuchiya et al. 2010) have indicated that iron absorption was decreased in DIOS patients without altering the level of serum iron, indicating that the hepatic iron overload may be associated with cellular iron uptake, which is…”
ResultHepcidin and Its Role in Iron Homeostasis.
Kwapisz, J., Słomka, A., & Żekanowska, E. (2009) · PubMed Central · Cited by 19 · see citing works
ACQUIRED REFRACTORY IRON DEFICIENCY
Amicis, M. M. D., Rimondi, A., Elli, L., & Motta, I. (2021) · Mediterranean Journal of Hematology and Infectious Diseases · doi:10.4084/mjhid.2021.028 · Cited by 18 · see citing works
“levels and contribute to ID; the iron intake becomes inadequate to major requirement due to a higher blood volume.(41,42) Several studies proved a reduced iron intake after bariatric surgery, primarily due to increased satiety and”
BackgroundChang, T., Liu, K., Chang, C. S., Su, C., Chen, S., Lee, Y., & Chang, J. (2017) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.201700442 · Cited by 17 · see citing works
“Although obese people are at a high risk of iron deficiency [12], they are reported to exhibit iron accumulation in the liver [13, 14] or brain [15].”
BackgroundHepcidin and its potential clinical utility
Miseta, A., Nagy, J., Nagy, T., Poór, V. S., Fekete, Z., & Sipos, K. (2015) · Cell Biology International · doi:10.1002/cbin.10505 · Cited by 16 · see citing works
“Ruivard et al. (2009) showed that decreased iron absorption in overweight persons could be attributed to elevated hepcidin levels.”
BackgroundChanges in serum hepcidin levels in acute iron intoxication in a rat model
Ben–Assa, E., Youngster, I., Kozer, E., Abu‐Kishk, I., Bar-Haim, A., Bar‐Oz, B., & Berkovitch, M. (2009) · Toxicology Letters · doi:10.1016/j.toxlet.2009.06.848 · Cited by 15 · see citing works
Barbalho, S. M., Laurindo, L. F., Tofano, R. J., Flato, U. A. P., Mendes, C. G., Goulart, R. D. Á., Briguezi, A. M. G. M., & Bechara, M. D. (2023) · Endocrines · doi:10.3390/endocrines4010002 · Cited by 14 · see citing works
A novel mutation in the SLC40A1 gene associated with reduced iron export in vitro
Moreno‐Carralero, M., Muñoz‐Muñoz, J., Cuadrado‐Grande, N., López‐Rodríguez, R., Hernández‐Alfaro, M. J., del‐Castillo‐Rueda, A., de Salamanca, R. E., Méndez, M., & Morán‐Jiménez, M. (2014) · American Journal of Hematology · doi:10.1002/ajh.23714 · Cited by 14 · see citing works
Lobbes, H., Gladine, C., Mazur, A., Pereira, B., Dualé, C., Cardot, J., & Ruivard, M. (2019) · Clinical Nutrition · doi:10.1016/j.clnu.2019.02.012 · Cited by 14 · see citing works
“The pathophysiology 98 remains unclear: although the hepcidin level is consistent with iron storage leading to 99 decreased iron absorption (10), iron accumulation could occur during the phase of increased 100 iron availability at the onset of weight gain, as supported by animal experimentation (11).”
BackgroundResultSelf-citationFerritinophagy: A new idea for liver diseases regulated by ferroptosis
Qian, Z., Li, J., Xiong, W., & Mao, X. (2023) · Hepatobiliary & pancreatic diseases international · doi:10.1016/j.hbpd.2023.10.005 · Cited by 12 · see citing works
Mariani, R., Pelucchi, S., Arosio, C., Coletti, S., Pozzi, M., Paolini, V., Trombini, P., & Piperno, A. (2010) · Blood Cells Molecules and Diseases · doi:10.1016/j.bcmd.2010.01.002 · Cited by 12 · see citing works
Démarche diagnostique devant une hyperferritinémie
Lorcerie, B., Audia, S., Samson, M., Millière, A., Falvo, N., Seguin, V. L., Berthier, S., & Bonnotte, B. (2015) · La Revue de Médecine Interne · doi:10.1016/j.revmed.2014.12.007 · Cited by 12 · see citing works
Tallec-Estève, N. L., Rousseau, C., Desrues, B., Loréal, O., & Thibault, R. (2020) · Clinical Nutrition · doi:10.1016/j.clnu.2020.06.007 · Cited by 10 · see citing works
MRI quantification of splenic iron concentration in mouse
Hitti, E., Eliat, P., Abgueguen, E., Ropert, M., Leroyer, P., Brissot, P., Gandon, Y., Saint‐Jalmes, H., & Loréal, O. (2010) · Journal of Magnetic Resonance Imaging · doi:10.1002/jmri.22290 · Cited by 10 · see citing works
“clinical situations in which hepcidin levels are abnormal, including dysmetabolic hepatosiderosis (20), could benefit from their diagnosis and a follow-up of splenic iron concentration determination.”
BackgroundIron absorption in nonalcoholic steatohepatitis and dysmetabolic iron overload syndrome
Ruivard, M., Lainé, F., & Deugnier, Y. (2015) · Hepatology · doi:10.1002/hep.28296 · Cited by 10 · see citing works
Self-citationBloomer, S. A., Olivier, A. K., Bergmann, O. M., Mathahs, M. M., Broadhurst, K. A., Hicsasmaz, H., & Brown, K. E. (2016) · Cell Biochemistry and Function · doi:10.1002/cbf.3238 · Cited by 9 · see citing works
“One study of patients with dysmetabolic iron overload syndrome, many of whom have NASH, reported that urinary hepcidin levels correlated more closely with HICs than did hepatic hepcidin mRNA levels,(42) while another found that plasma hepcidin correlated most closely with iron absorption in this population.(8) Importa…”
BackgroundResultIron, the Essential Micronutrient: A Comprehensive Review of Regulatory Pathways of Iron Metabolism
Horváth, A., Tamási, K., Pap, R., Jánosa, G., & Pandur, E. (2025) · Nutrients · doi:10.3390/nu18010109 · Cited by 10 · see citing works
“Increased levels of TNF-α and IL-6 lead to a rise in HAMP expression and the secretion of hepcidin, which is followed by the reduced expression of FPN, leading to iron accumulation in the hepatocytes and macrophages [135,136].”
Hepcidin induction limits mobilisation of splenic iron in a mouse model of secondary iron overload
Camberlein, E., Abgueguen, E., Fatih, N., Canonne‐Hergaux, F., Leroyer, P., Turlin, B., Ropert, M., Brissot, P., & Loréal, O. (2010) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2009.12.007 · Cited by 8 · see citing works
“We then mobilised iron stores with mild phlebotomies that mimicked those performed in human patients, especially during dysmetabolic hepatosiderosis in which hepcidin expression is increased [34].”
BackgroundDoes iron overload in metabolic syndrome affect macrophage profile? A case control study
Lahaye, C., Gladine, C., Pereira, B., Berger, J., Chinetti, G., Lainé, F., Mazur, A., & Ruivard, M. (2021) · Journal of Trace Elements in Medicine and Biology · doi:10.1016/j.jtemb.2021.126786 · Cited by 7 · see citing works
Self-citationMartinelli, N., Traglia, M., Campostrini, N., Biino, G., Corbella, M., Sala, C. F., Busti, F., Masciullo, C., Manna, D., Previtali, S., et al. (2013) · PLoS ONE · doi:10.1371/annotation/233a5ac3-8118-4bdc-a139-950223506864 · Cited by 7 · see citing works
Association of Habitual Dietary Intake with Liver Iron—A Population-Based Imaging Study
Filler, J., von Krüchten, R., Wawro, N., Maier, L., Lorbeer, R., Nattenmüller, J., Thorand, B., Bamberg, F., Peters, A., Schlett, C. L., et al. (2021) · Nutrients · doi:10.3390/nu14010132 · Cited by 6 · see citing works
“Furthermore, duodenal iron uptake is reduced in DIOS, again suggesting a relationship with increased liver fat [53].”
BackgroundRueda, A. D. C., Moreno‐Carralero, M., Cuadrado‐Grande, N., Méndez, M., & Morán‐Jiménez, M. (2011) · Medicina Clínica · doi:10.1016/j.medcli.2011.02.023 · Cited by 5 · see citing works
Diagnostic et traitement d’une surcharge en fer
Ruivard, M., & Lobbes, H. (2023) · La Revue de Médecine Interne · doi:10.1016/j.revmed.2023.07.002 · Cited by 5 · see citing works
Self-citationHepcidin: An emerging hormone in iron homeostasis: A review
Karoriya, A. K., Jain, A., Kumar, R., & Shakkarpude, J. (2021) · International Journal of Chemical Studies · doi:10.22271/chemi.2021.v9.i1ai.11600 · Cited by 4 · see citing works
“The synthesis of hepcidin in hepatocytes can be regulated by iron overload, inflammatory signals, increased erythropoiesis, hypoxia and anemia (Ruivard et al., 2009) [22].”
BackgroundJeong, H., Lee, C., Han, S. Y., Ko, Y.-J., & Kim, K. J. (2023) · Korean Journal of Family Practice · doi:10.21215/kjfp.2023.13.1.15 · Cited by 4 · see citing works
Surcharges héréditaires en fer
Brissot, P., Bardou‐Jacquet, E., Latournerie, M., Ropert, M., Island, M., Loréal, O., & Jouanolle, A. (2009) · Pathologie Biologie · doi:10.1016/j.patbio.2009.10.011 · Cited by 4 · see citing works
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de Oliveira, P. M., Espósito, B. P., Carvente, C. T., da Silva, G. A., Dellavance, A., Baldo, D. C., & Ferraz, M. L. G. (2022) · European Journal of Gastroenterology & Hepatology · doi:10.1097/meg.0000000000002416 · Cited by 3 · see citing works
Hémochromatoses et autres surcharges hépatiques en fer
Deugnier, Y., Lainé, F., Lan, C. L., Bardou‐Jacquet, E., Jouanolle, A., & Brissot, P. (2011) · EMC - Hépatologie · doi:10.1016/s1155-1976(11)40364-8 · Cited by 3 · see citing works
Self-citationDiagnostic d’une surcharge hépatique en fer
Deugnier, Y., Bardou‐Jacquet, E., Lainé, F., Gandon, Y., & Jouanolle, A. (2012) · La Revue de Médecine Interne · doi:10.1016/j.revmed.2012.03.007 · Cited by 4 · see citing works
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Iron deficiency states in metabolically burdened women in the pregravid period
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Hierro y riesgo vascular residual dependiente del perfil lipídico: una relación olvidada
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Stéato-hépatite, surcharge en fer et insulinorésistance
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Gute Prognose bei Therapie der Hämochromatose im Frühstadium
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Miyanishi, K., Kobune, M., & Kato, J. (2015) · Hepatology · doi:10.1002/hep.28290
“The study reported by Ruivard et al.((1)) differed markedly from our own,((2)) the major difference being the study subjects.”
ResultInfluentialAssessment of plasma catecholamines in patients with dysmetabolic iron overload syndrome
Hanna, H. W. Z., Baz, H., Al‐Kzayer, L. F. Y., Haddad, H. E. E., & El‐Mougy, F. (2022) · Journal of Applied Biomedicine · doi:10.32725/jab.2022.016
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“It occurs due to chronic anemia, significant iron overload [2–6], folic acid deficiency, vitamin D deficiency, suboptimal chelation, endocrinopathies, e.g. hypothyroidism [7–11], associated chronic diseases (such as chronic liver and kidney diseases) and zinc deficiency [12].”
Spector, A. R. (2025) · Journal of Clinical Sleep Medicine · doi:10.5664/jcsm.11912
Fu, Y., Fang, J., Ge, Y., Zhang, S., Liu, Y., Zhou, G., Yuan, X., Jiao, N., Li, Y., & Yang, W. (2025) · Scientific Reports · doi:10.1038/s41598-025-22609-8
- Authors
- Ruivard, M., Lainé, F., Ganz, T., Olbina, G., Westerman, M., Nemeth, E., Rambeau, M., Mazur, A., Gerbaud, L., Tournilhac, V., Abergel, A., Philippe, P., Deugnier, Y., & Coudray, C.
- Affiliations
- Centre Hospitalier Universitaire de Clermont-Ferrand (FR)
- Inserm (FR)
- University of California, Los Angeles (US)
- Intrinsic LifeSciences (United States) (US)
- Centre de Recherche en Nutrition Humaine d'Auvergne (FR)
- Corresponding author
- Ruivard, Marc
- ORCID
- Venue
- Journal of Hepatology
- Publisher
- Elsevier BV
- Published
- 2009-06
- Volume
- 50
- Issue
- 6
- Pages
- 1219-1225
- ISSN
- 0168-8278 (ISSN-L)
- OpenAlex
- W1966217648
- Cited by
- 89
- References
- 32
- Citations by year
- 2025: 6 · 2024: 1 · 2023: 5 · 2022: 2 · 2021: 5 · 2020: 2 · 2019: 2 · 2018: 4 · 2017: 4 · 2016: 4 · 2015: 9 · 2014: 6 · 2013: 5 · 2012: 11
- FWCI
- 7.55
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Hepatology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Life Sciences › Neuroscience › Neurology › Neurological diseases and metabolism
- Health Sciences › Nursing › Nutrition and Dietetics › Trace Elements in Health
- Keywords
- intestinal iron absorption, hepcidin, iron overload, insulin resistance, HOMA, C-reactive protein, overweight
- MeSH terms
- Adult, Aged, Humans, Insulin Resistance, Intestinal Absorption, Iron Isotopes, Male, Middle Aged, Syndrome, Case-Control Studies, Iron Overload, Iron, Dietary, Antimicrobial Cationic Peptides, Overweight, Hepcidins
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