Dysregulation of systemic iron metabolism in alcoholic liver diseases
Abstract
Alcoholic liver diseases (ALD) are frequently associated with iron overload. Until recently, the effects of ethanol in hepatic iron uptake and intestinal iron absorption have not been clarified in detail. Two possible mechanisms for iron overload are the uptake of iron into hepatocytes in a specific manner through the increased expression of transferrin receptor (TfR) 1; and increased intestinal iron absorption by the lowering of hepcidin. It is worthwhile to examine whether a similar mechanism is present in the development of steatosis and non‐alcoholic steatohepatitis (NASH). Hepatocytes have several iron uptake pathways. Ethanol increases transferrin (Tf)‐mediated uptake via a receptor‐dependent manner, but downregulates the non‐Tf‐bound iron uptake. According to immunohistochemical study, TfR1 was increased in hepatocytes in 80% of hepatic tissues of patients with ALD, but was not detected in normal hepatic tissues. In an experimental model, ethanol exposure to the primary cultured‐hepatocytes in the presence of iron increased TfR1 expression and 59 Fe‐labeled Tf uptake. In patients with ALD, intestinal iron absorption is increased by oral iron uptake assay. The regulatory hormone for iron homeostasis, hepcidin is downregulated in ethanol‐loaded mice liver. As well as ALD, a similar mechanism was present in the mouse model fed with a high‐fat diet, a model of the initial phenomenon of steatosis. The common mechanism for hepatic iron deposition and the triggering role of iron may be present in the development of ALD and non‐alcoholic fatty liver disease/NASH.
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In alcoholic liver disease, both iron and alcohol contribute to the production of hepatic fibrosis.
“Specifically, in alcoholic liver disease, both iron and alcohol contribute to the production of hepatic fibrosis [1352-1358].”
From Iron behaving badly: inappropriate iron chelation as a major contributor to the aetiology of vascular and other progressive inflammatory and degenerative diseases (2009) · cites this paper as [1358]
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- Authors
- Kohgo, Y., Ohtake, T., Ikuta, K., Suzuki, Y., Torimoto, Y., & Kato, J.
- Affiliations
- Asahikawa Medical University (JP)
- Sapporo Medical University (JP)
- Corresponding author
- Kohgo, Yutaka
- Venue
- Journal of Gastroenterology and Hepatology
- Publisher
- Wiley
- Published
- 2008-03
- Volume
- 23
- Issue
- s1
- Pages
- S78-81
- ISSN
- 0815-9319 (ISSN-L)
- 1440-1746
- OpenAlex
- W2069517565
- Cited by
- 66
- References
- 26
- Citations by year
- 2025: 3 · 2024: 2 · 2023: 1 · 2022: 4 · 2021: 2 · 2020: 1 · 2019: 2 · 2018: 4 · 2017: 4 · 2016: 3 · 2015: 2 · 2014: 6 · 2013: 7 · 2012: 5
- FWCI
- 4.31
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Gastroenterology and Hepatology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Japan Society for the Promotion of Science (20590754)
- Topics
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
- Health Sciences › Nursing › Nutrition and Dietetics › Trace Elements in Health
- Keywords
- alcoholic liver disease, iron overload, iron metabolism, transferrin receptor 1, hepcidin, ethanol, intestinal iron absorption, nonalcoholic steatohepatitis, hepatic steatosis, non-alcoholic fatty liver disease, iron homeostasis
- MeSH terms
- Animals, Liver Diseases, Alcoholic, Iron Metabolism Disorders, Mice
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