Modeling the dynamics of mouse iron body distribution: hepcidin is necessary but not sufficient
Open accessPublished version of a preprint
Abstract
BACKGROUND: Iron is an essential element of most living organisms but is a dangerous substance when poorly liganded in solution. The hormone hepcidin regulates the export of iron from tissues to the plasma contributing to iron homeostasis and also restricting its availability to infectious agents. Disruption of iron regulation in mammals leads to disorders such as anemia and hemochromatosis, and contributes to the etiology of several other diseases such as cancer and neurodegenerative diseases. Here we test the hypothesis that hepcidin alone is able to regulate iron distribution in different dietary regimes in the mouse using a computational model of iron distribution calibrated with radioiron tracer data. RESULTS: A model was developed and calibrated to the data from adequate iron diet, which was able to simulate the iron distribution under a low iron diet. However simulation of high iron diet shows considerable deviations from the experimental data. Namely the model predicts more iron in red blood cells and less iron in the liver than what was observed in experiments. CONCLUSIONS: These results suggest that hepcidin alone is not sufficient to regulate iron homeostasis in high iron conditions and that other factors are important. The model was able to simulate anemia when hepcidin was increased but was unable to simulate hemochromatosis when hepcidin was suppressed, suggesting that in high iron conditions additional regulatory interactions are important.
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Parameters can be used as a source of initial values when fitting a model to experimental data, as seen in BIOMD0000000734 (Parmar et al., 2017).
“In addition to the above example, parameters can be used as a source of initial values when fitting a model to the experimental data, as seen in BIOMD0000000734 (Parmar et al., 2017).”
From BioModels Parameters: a treasure trove of parameter values from published systems biology models (2020) · cites this paper as Parmar et al., 2017
The Methods (Modeling framework and computations; page unavailable) say the authors estimated model parameters to fit experimental data, and the Results (Parameter estimation for adequate iron diet; page unavailable) list the resulting parameter sets. Our copy does not say those parameters supplied initial values for fitting; it describes reusing initial species concentrations after a fit. It also identifies the deposited models as MODEL1605030002–MODEL1605030005, not BIOMD0000000734. (LLM, conf=0.84)
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“In addition to the above example, parameters can be used as a source of initial values when fitting a model to the experimental data, as seen in BIOMD0000000734 (Parmar et al., 2017).”
Method
- Authors
- Parmar, J. H., Davis, G., Shevchuk, H., & Mendes, P.
- Affiliations
- UConn Health (US)
- University of Manchester (GB)
- Corresponding author
- Mendes, Pedro
- Venue
- BMC Systems Biology
- Published
- 2017-05-18
- Volume
- 11
- Issue
- 1
- Pages
- 57-57
- ISSN
- 1752-0509 (ISSN-L)
- PMC
- PMC5437513
- OpenAlex
- W2951153302
- Cited by
- 12
- References
- 47
- Citations by year
- 2026: 1 · 2025: 2 · 2020: 4 · 2019: 3 · 2018: 2
- FWCI
- 1.87
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- BMC Systems Biology (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Research Explorer (The University of Manchester) (publishedVersion, other-oa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- Division of Mathematical Sciences (DMS-1460967)
- Topics
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Health Sciences › Nursing › Nutrition and Dietetics › Trace Elements in Health
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Ferroptosis and cancer prognosis
- Keywords
- hepcidin, iron homeostasis, iron distribution, mice, computational model, low-iron diet, high-iron diet, anemia, hemochromatosis, erythrocytes, liver iron, iron export
- MeSH terms
- Iron Deficiencies, Anemia, Animals, Chronic Disease, Diet, Hemochromatosis, Iron, Models, Biological, Phenotype, Mice, Hepcidins
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