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Mouse Iron Distribution - Rich and Deficient iron diets (tracer)

ABSTRACT: Mouse Iron Distribution Dynamics Dynamic model of iron distribution in mice. This model attempts to fit the radioiron tracer data from Lopes et al. 2010 for mice fed iron deficient and rich diets by adjusting the rate of iron intake (vDiet) and the hepcidin synthesis rate (vhepcidin) independently for each experiment. All other parameters are those that provide the best fit for the adequate diet. This model includes the radioiron tracer species. Differences in parameter values between deficient, rich, and adequate diets: Diet vDiet vhepcidin Adequate 0.00377422 1.7393e-08 Deficient 0 8.54927e-09 Rich 0.00415624 2.30942e-08

SUBMITTER: Krishna Kumar Tiwari

PROVIDER: BIOMD0000000734 | BioModels | 2024-09-02

REPOSITORIES: BioModels

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			Action	DRS
	BIOMD0000000734?filename=BIOMD0000000734.xml	Xml
	BIOMD0000000734?filename=Fig4_all.png	Other
	BIOMD0000000734?filename=Parmar2017_Deficient_Rich_tracer.cps	Other
	BIOMD0000000734?filename=Parmar2017_Deficient_Rich_tracer.sedml	Other

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Modeling the dynamics of mouse iron body distribution: hepcidin is necessary but not sufficient.

Parmar Jignesh H JH Davis Grey G Shevchuk Hope H Mendes Pedro P

BMC systems biology 20170518 1

<h4>Background</h4>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 dis ...[more]

PMID: 28521769

Publication: 1/2

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Project description:Iron is an essential nutritional element; its deficiency in the body causes nutritional problems and a decrease in iron storage that can lead to anemia. The liver not only stores iron but is an important metabolic target as well. Dietary iron deficiency is associated with changes in the metabolism of nutrients such as lipids. However, to the best of our knowledge, a global analysis detailing the consequences of iron deficiency in the body has not yet been reported. We performed a comprehensive transcriptome analysis using DNA microarray technology to reveal the effects of iron deficiency on hepatic gene expression. Four-week-old rats were fed an iron-deficient diet or a control diet for 16 days. On day 17, the rats were sacrificed under anesthesia, and their livers were dissected for DNA microarray analysis. We identified 600 up-regulated and 500 down-regulated probe sets to characterize the iron-deficient diet group. The up-regulated probe sets contained genes for enzymes that are involved in cholesterol, amino acid, and glucose metabolisms, as well as in apoptosis. The down-regulated probe sets included genes for enzymes associated with lipid metabolism. Additionally, the 16-day iron-deficient diet induced anemia. Our gene expression analysis revealed that, as a result, cholesterol biosynthesis, gluconeogenesis, and apoptosis due to endoplasmic reticulum stress were accelerated, while fatty acid biosynthesis was suppressed by dietary iron deficiency. Our analysis also showed that cholesterol metabolism, including bile acid biosynthesis, was accelerated in the initial stages of cholesterol accumulation. Experiment Overall Design: Male 3-week-old Sprague Dawley rats were purchased from Charles River Japan (Kanagawa, Japan) and housed in a room conditioned at 24 Â± 1Â°C and 40 Â± 5% humidity with a 12-h light-dark cycle (lights on at 08:00). The rats were given a control diet and water for 24 h ad libitum. Diets for rats were obtained from Research Diets, Inc. (New Brunswick, NJ, USA). The composition of the control diet was based on the AIN93G diet , except that cellulose was replaced by Avicel, since cellulose is an ingredient of variable iron content. The iron-deficient diet was prepared by removal of iron (ferric citrate) from the control diet. At day 8, rats were divided into two groups comprising animals of similar body weights. One group (n = 6) was fed the control diet and the other group (n = 7) was fed the iron-deficient diet (iron-deficient diet group). After iron-deficient diet feeding was started, blood hemoglobin levels were measured every two days. Blood samples for hemoglobin measurements were collected from the tail vein, and hemoglobin levels were measured by using the Wako Hemoglobin B test (Wako Pure Chemical Industries, Osaka, Japan). On day 12 of the iron-deficient diet treatment, diets were removed at 17:00, and feeding was conducted between 09:00 and 17:00 for another 4 days. This protocol was intended to synchronize the ratsâ feeding behavior. On day 17 of the iron-deficient diet treatment, rats were fed for 1.5 h prior to sacrifice under anesthesia. Livers were then excised and subsequently immersed in RNAlater (Applied Biosystems Japan, Tokyo, Japan). Blood hemoglobin level of rats fed an iron-deficient diet decreased significantly over the course of the feeding. On day 17, the hemoglobin level in the iron-deficient diet group was 42% of that of the control diet group (P < 0.01).

Project description:This a model from the article: Systems analysis of iron metabolism: the network of iron pools and fluxes Tiago JS Lopes, Tatyana Luganskaja, Maja Vujic-Spasic, Matthias W Hentze, Martina U Muckenthaler, K laus Schumann and Jens G Reich BMC Systems Biology2010, Aug 13;4(1):112. 20704761, Abstract: Background Every cell of the mammalian organism needs iron in numerous oxido-reductive processes as well as fo r transport and storage of oxygen. The versatility of ionic iron makes it a toxic entity which can catalyze the production of radicals that damage vital membranous and macromolecular assemblies in t he cell. The mammalian organism maintains therefore a complex regulatory network of iron uptake, ex cretion and intra-body distribution. Intracellular regulation in different cell types is intertwine d with a global hormonal signaling structure. Iron deficiency as well as excess of iron are frequen t and serious human disorders. They can affect every cell, but also the organism as a whole. Results Here, we present a kinematic model of the dynamic system of iron pools and fluxes. It is based on f errokinetic data and chemical measurements in C57BL6 wild-type mice maintained on iron-deficient, i ron-adequate, or iron-loaded diet. The tracer iron levels in major tissues and organs (16 compartme nt) were followed for 28 days. The evaluation resulted in a whole-body model of fractional clearanc e rates. The analysis permits calculation of absolute flux rates in the steady-state, of iron distr ibution into different organs, of tracer-accessible pool sizes and of residence times of iron in th e different compartments in response to three states of iron-repletion induced by the dietary regim e. Conclusions This mathematical model presents a comprehensive physiological picture of mice under three differen t diets with varying iron contents. The quantitative results reflect systemic properties of iron me tabolism: dynamic closedness, hierarchy of time scales, switch-over response and dynamics of iron s torage in parenchymal organs. Therefore, we could assess which parameters will change under dietary perturbations and study in quantitative terms when those changes take place. This model corresponds to the Iron Adequate condition - Mice This model originates from BioModels Database: A Database of Annotated Published Models. It is copyright (c) 2005-2010 The BioModels Team.For more information see the terms of use.To cite BioModels Database, please use Le Novère N., Bornstein B., Broicher A., Courtot M., Donizelli M., Dharuri H., Li L., Sauro H., Schilstra M., Shapiro B., Snoep J.L., Hucka M. (2006) BioModels Database: A Free, Centralized Database of Curated, Published, Quantitative Kinetic Models of Biochemical and Cellular Systems Nucleic Acids Res., 34: D689-D691.