Is the iron regulatory hormone hepcidin a risk factor for alcoholic liver disease?
Open accessAbstract
Despite heavy consumption over a long period of time, only a small number of alcoholics develop alcoholic liver disease. This alludes to the possibility that other factors, besides alcohol, may be involved in the progression of the disease. Over the years, many such factors have indeed been identified, including iron. Despite being crucial for various important biological processes, iron can also be harmful due to its ability to catalyze Fenton chemistry. Alcohol and iron have been shown to interact synergistically to cause liver injury. Iron-mediated cell signaling has been reported to be involved in the pathogenesis of experimental alcoholic liver disease. Hepcidin is an iron-regulatory hormone synthesized by the liver, which plays a pivotal role in iron homeostasis. Both acute and chronic alcohol exposure suppress hepcidin expression in the liver. The sera of patients with alcoholic liver disease, particularly those exhibiting higher serum iron indices, have also been reported to display reduced prohepcidin levels. Alcohol-mediated oxidative stress is involved in the inhibition of hepcidin promoter activity and transcription in the liver. This in turn leads to an increase in intestinal iron transport and liver iron storage. Hepcidin is expressed primarily in hepatocytes. It is noteworthy that both hepatocytes and Kupffer cells are involved in the progression of alcoholic liver disease. However, the activation of Kupffer cells and TNF-alpha signaling has been reported not to be involved in the down-regulation of hepcidin expression by alcohol in the liver. Alcohol acts within the parenchymal cells of the liver to suppress the synthesis of hepcidin. Due to its crucial role in the regulation of body iron stores, hepcidin may act as a secondary risk factor in the progression of alcoholic liver disease. The clarification of the mechanisms by which alcohol disrupts iron homeostasis will allow for further understanding of the pathogenesis of alcoholic liver disease.
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Alcohol-induced oxidative stress in hepatocytes downregulates hepcidin expression in liver, by altering transcription factor C/EBP activity, thus dysregulating iron homeostasis.
“Although the mechanisms underlying iron accumulation are not well understood, it has been reported that alcohol-induced oxidative stress in hepatocytes downregulates hepcidin expression in liver, by altering transcription factor C/EBP activity, thus dysregulating iron homeostasis (Hou et al., 2009;Harrison-Findik, 2009).”
From Iron, Oxidative Stress and Health (2012) · cites this paper as Harrison-Findik, 2009
Mitochondrial DNA damage and ribosomal defects may inhibit mitochondrial protein synthesis and compromise oxidative phosphorylation in chronic alcohol consumption.
“Harrison-Findik(2009) suggested that mitochondrial DNA damage and ribosomal defects may inhibit mitochondrial protein synthesis and compromise oxidative phosphorylation in chronic alcohol consumption.”
From Iron, Oxidative Stress and Health (2012) · cites this paper as Harrison-Findik(2009)
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Iron, Oxidative Stress and Health
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- Authors
- Harrison-Findik, D.-D.
- Affiliations
- University of Nebraska Medical Center (US)
- Corresponding author
- Harrison-Findik, Duygu-Dee
- Venue
- World Journal of Gastroenterology
- Publisher
- Baishideng Publishing Group Inc.
- Published
- 2009
- Volume
- 15
- Issue
- 10
- Pages
- 1186
- ISSN
- 1007-9327 (ISSN-L)
- PMC
- PMC2658862
- OpenAlex
- W2099217986
- Cited by
- 56
- References
- 20
- Citations by year
- 2026: 4 · 2025: 1 · 2024: 2 · 2023: 5 · 2022: 3 · 2021: 2 · 2020: 1 · 2019: 1 · 2018: 5 · 2017: 3 · 2016: 2 · 2015: 1 · 2014: 3 · 2013: 2 · 2012: 8
- FWCI
- 1.02
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- World Journal of Gastroenterology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of Nebraska-Lincoln
- National Institutes of Health
- National Institute on Alcohol Abuse and Alcoholism (R01AA017738)
- National Center for Research Resources (P20RR017675)
- 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
- hepcidin, alcoholic liver disease, iron homeostasis, oxidative stress, Fenton reaction, hepatocytes, Kupffer cells, TNF signaling, serum iron, liver iron storage, intestinal iron absorption, disease progression
- MeSH terms
- Ethanol, Homeostasis, Iron, Kupffer Cells, Liver Diseases, Alcoholic, Promoter Regions, Genetic, Risk Factors, Transcription, Genetic, Down-Regulation, Antimicrobial Cationic Peptides, Hepcidins
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