Sex Differences in Iron Status and Hepcidin Expression in Rats

Studies have shown that men and women exhibit significant differences regarding iron status. However, the effects of sex on iron accumulation and distribution are not well established. In this study, female and male Sprague-Dawley rats were killed at 4 months of age. Blood samples were analyzed to determine the red blood cell (RBC) count, hemoglobin (Hb) concentration, hematocrit (Hct), and mean red blood cell volume (MCV). The serum samples were analyzed to determine the concentrations of serum iron (SI), transferrin saturation (TS), ferritin, soluble transferrin receptor (sTfR), and erythropoietin (EPO). The tissue nonheme iron concentrations were measured in the liver, spleen, bone marrow, kidney, heart, gastrocnemius, duodenal epithelium, lung, pallium, cerebellum, hippocampus, and striatum. Hepatic hepcidin expression was detected by real-time PCR analysis. The synthesis of ferroportin 1 (FPN1) in the liver, spleen, kidney, and bone marrow was determined by Western blot analysis. The synthesis of duodenal cytochrome B561 (DcytB), divalent metal transporter 1 (DMT1), FPN1, hephaestin (HP) in the duodenal epithelium was also measured by Western blot analysis. The results showed that the RBC, Hb, and Hct in male rats were higher than those in female rats. The SI and plasma TS levels were lower in male rats than in female rats. The levels of serum ferritin and sTfR were higher in male rats than in female rats. The EPO levels in male rats were lower than that in female rats. The nonheme iron contents in the liver, spleen, bone marrow, and kidney in male rats were also lower (56.7, 73.2, 60.6, and 61.4 % of female rats, respectively). Nonheme iron concentrations in the heart, gastrocnemius, duodenal epithelium, lung, and brain were similar in rats of both sexes. A moderate decrease in hepatic hepcidin mRNA content was also observed in male rats (to 56.0 % of female rats). The levels of FPN1 protein in the liver, spleen, and kidney were higher in male rats than in female rats. There was no significant change in FPN1 expression in bone marrow. Significant difference was also not found in DcytB, DMT1, FPN1, and HP protein levels in the duodenal epithelium between male and female rats. These data suggest that iron is distributed differently in male and female rats. This difference in iron distribution may be associated with the difference in the hepcidin level.     

Iron and cadmium uptake by duodenum of hypotransferrinaemic mice

Absorption from food is an important route for entry of the toxic metal, cadmium, into the body. Both cadmium and iron are believed to be taken up by duodenal enterocytes via the iron regulated, proton-coupled transporter, DMT1. This means that cadmium uptake could be enhanced in conditions where iron absorption is increased. We measured pH dependent uptake of ¹⁰⁹Cd and ⁵⁹Fe by duodenum from mice with an in vitro method. Mice with experimental (hypoxia, iron deficiency) or hereditary (hypotransferrinaemia) increased iron absorption were studied. All three groups of mice showed increased ⁵⁹Fe uptake (p<0.05) compared to their respective controls. Hypotransferrinaemic and iron deficient mice exhibited an increase in ¹⁰⁹Cd uptake (p<0.05). Cadmium uptake was not, however, increased by lowering the medium pH from 7.4 to 6. In contrast, ⁵⁹Fe uptake (from ⁵⁹FeNTA₂) and ferric reductase activity was increased by lowering medium pH in control and iron deficient mice (p<0.05). The data show that duodenal cadmium uptake can be increased by hereditary iron overload conditions. The uptake is not, however, altered by lowering medium pH suggesting that DMT1-independent uptake pathways may operate.     

Iron absorption and hepatic iron uptake are increased in a transferrin receptor 2 (Y245X) mutant mouse model of hemochromatosis type 3

Hereditary hemochromatosis type 3 is an iron (Fe)-overload disorder caused by mutations in transferrin receptor 2 (TfR2). TfR2 is expressed highly in the liver and regulates Fe metabolism. The aim of this study was to investigate duodenal Fe absorption and hepatic Fe uptake in a TfR2 (Y245X) mutant mouse model of hereditary hemochromatosis type 3. Duodenal Fe absorption and hepatic Fe uptake were measured in vivo by 59Fe-labeled ascorbate in TfR2 mutant mice, wild-type mice, and Fe-loaded wild-type mice (2% dietary carbonyl Fe). Gene expression was measured by real-time RT-PCR. Liver nonheme Fe concentration increased progressively with age in TfR2 mutant mice compared with wild-type mice. Fe absorption (both duodenal Fe uptake and transfer) was increased in TfR2 mutant mice compared with wild-type mice. Likewise, expression of genes participating in duodenal Fe uptake (Dcytb, DMT1) and transfer (ferroportin) were increased in TfR2 mutant mice. Nearly all of the absorbed Fe was taken up rapidly by the liver. Despite hepatic Fe loading, hepcidin expression was decreased in TfR2 mutant mice compared with wild-type mice. Even when compared with Fe-loaded wild-type mice, TfR2 mutant mice had increased Fe absorption, increased duodenal Fe transport gene expression, increased liver Fe uptake, and decreased liver hepcidin expression. In conclusion, despite systemic Fe loading, Fe absorption and liver Fe uptake were increased in TfR2 mutant mice in association with decreased expression of hepcidin. These findings support a model in which TfR2 is a sensor of Fe status and regulates duodenal Fe absorption and liver Fe uptake.     

Molecular analysis of increased iron status in moderately exercised rats

Although iron plays a critical role in exercise, the regulatory mechanism of iron metabolism remains poorly understood. The aims of the present study were to investigate the effects of different intensity exercise on body iron status and the regulatory mechanism of duodenal iron absorption. Thirty female Sprague-Dawley rats (90–100 g) were randomly divided into three groups: a control group (remained sedentary, CG), a moderately exercised group (swam 1.5 h/day, MG) and a strenuously exercised group (swam with different load, SG). Serum iron status, serum ferritin and Hct were examined after 10 weeks of swimming. Western blot was performed to detect the expression of iron transport proteins: divalent metal transporter1 (DMT1) and ferroportin 1 (FPN1) in duodenal epithelium. The expression of hepcidin mRNA in liver was examined by RT-PCR. The results showed: (1) the body iron status in MG was kept at a high level compared to that of CG and SG, (2) Western blot showed DMT1 with iron responsive element (IRE) and FPN1 in duodenal epithelium which were higher in MG than that of CG and (3) the expression of hepatic hepcidin mRNA was down regulated in MG (p < 0.05). The data suggested that moderate exercise improved iron status and that was likely regulated by increased DMT1 with IRE and FPN1 expression. Hepcidin signaling pathway may involve in the regulation of duodenal iron absorption proteins. Xiang Lin Duan and Yan Zhong Chang share Senior Authorship     

长期游泳运动对大鼠铁状态的影响

目的：观察不同的运动时间对铁状态的影响。方法：大鼠随机分为3、6、12个月的三个游泳运动组和相应安静组;运动期满后观察血液学铁状态指标和器官非血红素铁(NHI)含量和NHI总含量(TNHI)的变化。结果：与安静组相比,三种不同时间长度的运动均诱导一种具有血浆铁浓度降低、血浆转铁蛋白铁饱和度降低而血红蛋白浓度和红细胞比容得到雏持的血液学低铁状态;这种低铁状态伴有肝、脾、心、肾NHI浓度显著降低,但与运动时间无关;肝、脾和肾TNHI变化与其浓度变化方向一致,但心脏没有显著变化;上述器官TNHI随时间增加而增多。结论：尽管运动诱导的低铁状态类似于铁缺乏中期表现,但由于器官NHI重分布和铁贮存并没有进行性降低,因此,长期运动引起的低铁状态可能是机体内铁代谢对运动的适应,不存在所谓“运动性铁缺乏”现象。     

Lack of Plasma Protein Hemopexin Results in Increased Duodenal Iron Uptake

Purpose

The body concentration of iron is regulated by a fine equilibrium between absorption and losses of iron. Iron can be absorbed from diet as inorganic iron or as heme. Hemopexin is an acute phase protein that limits iron access to microorganisms. Moreover, it is the plasma protein with the highest binding affinity for heme and thus it mediates heme-iron recycling. Considering its involvement in iron homeostasis, it was postulated that hemopexin may play a role in the physiological absorption of inorganic iron.

Methods and Results

Hemopexin-null mice showed elevated iron deposits in enterocytes, associated with higher duodenal H-Ferritin levels and a significant increase in duodenal expression and activity of heme oxygenase. The expression of heme-iron and inorganic iron transporters was normal. The rate of iron absorption was assessed by measuring the amount of ⁵⁷Fe retained in tissues from hemopexin-null and wild-type animals after administration of an oral dose of ⁵⁷FeSO₄ or of ⁵⁷Fe-labelled heme. Higher iron retention in the duodenum of hemopexin-null mice was observed as compared with normal mice. Conversely, iron transfer from enterocytes to liver and bone marrow was unaffected in hemopexin-null mice.

Conclusions

The increased iron level in hemopexin-null duodenum can be accounted for by an increased iron uptake by enterocytes and storage in ferritins. These data indicate that the lack of hemopexin under physiological conditions leads to an enhanced duodenal iron uptake thus providing new insights to our understanding of body iron homeostasis.     

The effect of 1 alpha, 25-dihydroxycholecalciferol on iron metabolism

Chronic administration of hypercalcemic doses of 1 alpha, 25-dihydroxycholecalciferol to intact, vitamin-D repleted rats for 4 weeks, enhanced net intestinal absorption of iron and liver iron stores. Daily net iron and calcium absorptions were found to be significantly correlated in both control and treated rats. In duodenal loop experiments, pretreatment with 1 alpha, 25-dihydroxycholecalciferol reversed the adverse effect of high Ca/Fe ratio on iron absorption. The increased intestinal absorption of iron did not result in a change of serum iron levels nor of total iron binding capacity due to the enhanced incorporation of absorbed iron into liver ferritin. The curve of uptake of 59Fe into circulating red cells of treated rats suggested retarded release of the isotope from stores. The hypothesis is advanced that the systemic metabolic defect (tissue hypoxia, raised erythropoietin levels) produced by 1 alpha, 25-dihydroxycholecalciferol is responsible for the disruption of the physiological coordination between iron stores and intestinal absorption.     

Interactions between tissue uptake of lead and iron in normal and iron-deficient rats during development

Environmental lead intoxication, which frequently causes neurological disturbances, and iron deficiency are clinical problems commonly found in children. Also, iron deficiency has been shown to augment lead absorption from the intestine. Hence, there is evidence for an interaction between lead and iron metabolism which could produce changes in lead and iron uptake by the brain and other tissues. These possibilities were investigated using 15-, 21-, and 63-old rats with varying nutritional iron and lead status. Dams were fed diets containing 0 or 3% lead-acetate and 0.2% lead-acetate in the drinking water. After weaning, 0.2% lead-acetate in the drinking water became the sole source of dietary lead. Measurements were made of tissue lead and nonheme iron levels and the uptake of⁵⁹Fe after intravenous injection of transferrin-bound⁵⁹Fe. Iron deficiency was associated with increased intestinal absorption of lead as indicated by blood and kidney lead levels in rats exposed to dietary lead. However, iron deficiency did not increase lead deposition in the brain, and in all rats brain lead levels were relatively low (<0.1 μg/g). Lead concentrations in the liver were below 2 μg/g, whereas kidneys had almost 20 times this concentration. Animals with iron deficiency had lower liver iron levels and had increased brain⁵⁹Fe uptake in comparison to control rats. However, iron levels in brain and kidneys were unaffected by lead intoxication regardless of the animal's iron status.⁵⁹Fe uptake rates were also unaffected by lead, but increased rates of uptake were apparent in iron-deficient rats. Lead did increase liver iron levels in all iron-adequate rats, but iron deficiency had little effect. It is concluded that, compared with other tissues, the blood-brain barrier largely restricts lead uptake by the brain and that the uptake that does occur is unrelated to the iron status of the animal. Also, the level of lead intoxication produced in this investigation did not influence iron uptake by the brain and kidneys, but liver iron stores could be incresed if iron levels were already adequate.     

Iron metabolism and placental iron transfer in the guinea pig

The interrelationship between fetal iron uptake and maternal iron metabolism has been studied in the guinea pig in the course of pregnancy. The rapid increase of the maternal need for iron during the period of fast increasing rates of placental iron transfer is largely compensated for by increased intestinal absorption. No enhanced mobilisation of iron from the liver and spleen iron stores could be demonstrated. The plasma iron turnover, corrected for the transplacental iron transfer rate, remained constant during pregnancy. This means that not only the mobilisation of iron from the stores remains principally unchanged, but also the supply of iron to the maternal organs and tissues. The haemoglobin concentration decreased by about 15% during the period of rapid fetal growth and iron uptake. The maternal blood volume increased during this very period and explained most of the observed reduction. Intestinal iron absorption increases. At day 55 of pregnancy placental iron transfer is maximal. It could be shown that a day 55 the rate of intestinal iron uptake equals the rate of iron transfer across the placentas. It is evident that pregnancy effects a direct influence on intestinal iron absorption, independent of the magnitude of the maternal iron stores. How this influence is realized without changing the iron kinetics of the maternal stores, cannot be explained with the prevailing theory.     

Iron bioavailability of common beans (Phaseolus vulgaris L.) intrinsically labeled with 59Fe

A radiobioassay was performed in rats with or without iron depletion to evaluate the iron bioavailability of diets enriched with common beans and with “multimixture”, a nutritional supplement based on parts of foods that are not usually eaten. The full-body ⁵⁹Fe level was determined after 5 h, the absorbed ⁵⁹Fe level was determined after 48 h, and the amount of ⁵⁹Fe retained was determined after 7 days. Iron bioavailability was assessed by the full-body radioactivity of the animals, determined using a solid scintillation detector. The iron bioavailability of common beans was higher in the iron-depleted animals (55.7%) than in the non-depleted animals (25.12%) because of the higher absorption rate in the iron-depleted animals. The multimixture did not influence dietary iron bioavailability. In addition, the iron bioavailability of common beans was similar to that observed in the standard source of iron for Wistar rats. Hence, common beans may be considered an adequate dietary iron source because of its high bioavailability.     

Total Iron and Heme Iron Content and their Distribution in Beef Meat and Viscera

To determine the content of total iron (TFe) and heme iron (HeFe) in major cuts of meat and principal viscera of bovine origin. ⁵⁵Fe (30 mCi) was injected into two 4-month-old calves. Triplicate samples of the 12 basic American cuts of meat and major viscera were obtained from each specimen. Samples were acid digested and their iron content was read by atomic absorption spectrophotometry. Duplicate samples of the basic cuts of meat and major viscera were analyzed to determine the concentration of ⁵⁵Fe using a double isotopic technique. The mean and standard deviation of TFe for all cuts was 1.4?±?0.3 mg/100 g of meat. The mean TFe for organs was (per mg/100 g): 0.9?±?0.1 brain, 3.0?±?0.05 kidney, 3.2?±?0.04 heart, 5.7?±?0.2 lung, 6.0?±?0.1 liver, and 31.2?±?0.4 spleen. HeFe was 64% of TFe in meat and 72.8% in spleen, 53.8% in lung, 35.7% in brain, 35.0% in kidney, 27.3% in heart, and only 13.6% in liver. Blood contained 85.5% of the radioisotope and only 1.4% was found in muscle and 1.6% was found in viscera. Results suggest that bovine cuts of meat have a low variation in TFe and that HeFe comprises more than 60% of TFe.     

Transitory hematologic effects of moderate exercise are not influenced by iron supplementation

A young women's exercise/fitness class tested the idea that administration of supplemental iron would prevent "sports anemia" that may develop during exercise and training and improve iron status of exercising females of menstrual age. Fifteen women (aged 18-37) were selected for each of three treatment groups: (1) no supplemental iron; (2) 9 mg X d-1 of Fe; and (3) 18 mg X d-1 of Fe (1 US Recommended Daily Allowance). Women exercised at approximately 85% of maximal heartrate for progressively increasing lengths of time in a jogging program and worked up to 45 min of exercise 4 d X week-1 for 8 weeks. Hematologic analysis was performed in weeks 1, 5, and 8. A significant decline in hemoglobin (Hb) concentration and hematocrit (Hct) was observed at week 5 when all data were examined without regard for iron intake; these red cell indices returned to pre-exercise levels by week 8. Reduction of mean cell hemoglobin concentration (MCHC) indicated that the midpoint decline was not caused by simple hemodilution during exercise. Serum ferritin (SF) concentration changed in parallel with Hb and Hct. Although the midpoint decline in SF was not statistically significant, it ruled out the possibility that turnover of red cell iron was directed to storage. Lowered MCHC and SF suggested lower availability of iron during the synthesis of a new generation of red cells. Few iron treatment effects of magnitude were observed. Iron did not prevent the midpoint decline in Hb concentration. Iron intake did not affect SF, serum iron, transferrin saturation, or final Hb, and Hct.(ABSTRACT TRUNCATED AT 250 WORDS)     

Heme Iron Uptake by Caco-2 Cells is a Saturable,Temperature Sensitive and Modulated by Extracellular pH and Potassium

It is known that heme iron and inorganic iron are absorbed differently. Heme iron is found in the diet mainly in the form of hemoglobin and myoglobin. The mechanism of iron absorption remains uncertain. This study focused on the heme iron uptake by Caco-2 cells from a hemoglobin digest and its response to different iron concentrations. We studied the intracellular Fe concentration and the effect of time, K⁺ depletion, and cytosol acidification on apical uptake and transepithelial transport in cells incubated with different heme Fe concentrations. Cells incubated with hemoglobin-digest showed a lower intracellular Fe concentration than cells grown with inorganic Fe. However, uptake and transepithelial transport of Fe was higher in cells incubated with heme Fe. Heme Fe uptake had a low V _max and K _m as compared to inorganic Fe uptake and did not compete with non-heme Fe uptake. Heme Fe uptake was inhibited in cells exposed to K⁺ depletion or cytosol acidification. Heme oxygenase 1 expression increased and DMT1 expression decreased with higher heme Fe concentrations in the media. The uptake of heme iron is a saturable and temperature-dependent process and, therefore, could occur through a mechanism involving both a receptor and the endocytic pathway.     

Prion Protein (PrP) Knock-Out Mice Show Altered Iron Metabolism: A Functional Role for PrP in Iron Uptake and Transport

Despite overwhelming evidence implicating the prion protein (PrP) in prion disease pathogenesis, the normal function of this cell surface glycoprotein remains unclear. In previous reports we demonstrated that PrP mediates cellular iron uptake and transport, and aggregation of PrP to the disease causing PrP-scrapie (PrP^Sc) form results in imbalance of iron homeostasis in prion disease affected human and animal brains. Here, we show that selective deletion of PrP in transgenic mice (PrP^KO) alters systemic iron homeostasis as reflected in hematological parameters and levels of total iron and iron regulatory proteins in the plasma, liver, spleen, and brain of PrP^KO mice relative to matched wild type controls. Introduction of radiolabeled iron (⁵⁹FeCl₃) to Wt and PrP^KO mice by gastric gavage reveals inefficient transport of ⁵⁹Fe from the duodenum to the blood stream, an early abortive spike of erythropoiesis in the long bones and spleen, and eventual decreased ⁵⁹Fe content in red blood cells and all major organs of PrP^KO mice relative to Wt controls. The iron deficient phenotype of PrP^KO mice is reversed by expressing Wt PrP in the PrP^KO background, demonstrating a functional role for PrP in iron uptake and transport. Since iron is required for essential metabolic processes and is also potentially toxic if mismanaged, these results suggest that loss of normal function of PrP due to aggregation to the PrP^Sc form induces imbalance of brain iron homeostasis, resulting in disease associated neurotoxicity.     

Acute Copper Supplementation Does Not Inhibit Non-Heme Iron Bioavailability in Humans

To measure the effect of acute copper (Cu) administration, given as an aqueous solution, on the absorption of iron (Fe), 29 healthy adult women participated in two iron absorption studies. Subjects received 0.5 mg of Fe, as ferrous sulfate, alone or with Cu, as copper sulfate, at 0.5:1, 1:1, or 2:1 Cu/Fe molar ratios (study I) or at 4:1, 6:1, or 8:1 Cu/Fe molar ratios (study II) as an aqueous solution on days 1, 2, 14, and 15 of the study. Fe absorption was assessed by erythrocyte incorporation of iron radioisotopes ⁵⁵Fe and ⁵⁹Fe. Geometric mean (range ± SD) absorption of Fe alone or at 0.5:1, 1:1, 2:1 Cu/Fe molar ratios were 34.4% (17.3–68.5%), 40.9% (24.9–67.2%), 48.3% (24.8–94.1%), and 50.2% (25.3–99.5%), respectively (ANOVA, p = 0.12). Geometric mean (range ± SD) absorption of Fe alone or at 4:1, 6:1, 8:1 Cu/Fe molar ratios were 28.7% (12.1–67.9%), 21.5% (6.5–71.5%), 29.6% (10.3–85.4%), and 36.5% (18.3–73.1%), respectively (ANOVA, p = 0.16). In conclusion, combined Cu and Fe administration in an aqueous solution does not inhibit Fe bioavailability. This information could help in the design of rational guidelines for copper and iron supplementation programs. Our results support the hypothesis that divalent metal transporter 1 is not physiologically relevant for copper absorption in humans.     

Influence of multistrain probiotic and iron supplementation on iron status in rats

ObjectiveThe impact of multistrain probiotics on iron (Fe) metabolism under Fe-deficient diet conditions remains unknown. The study aimed to compare the effect of 6 weeks simultaneous and exclusive oral multistrain probiotic and iron supplementation on selected parameters of Fe metabolism in rats on an Fe-deficient diet.MethodsForty rats were assigned to five groups, with eight animals in each, and for 6 weeks received: the CC group- a standard diet, the DD group- an Fe-deficient diet, the DPB group- an Fe-deficient with a multispecies probiotic, the DFE group- an Fe-deficient diet supplemented with iron, the DPBFE group- an Fe-deficient diet with iron and a multispecies probiotic. The Fe content in blood and tissues; serum concentration of erythroferrone, ferritin (Ft), homocysteine, hepcidin (HEPC) and lactoferrin; liver content of divalent metal transporter 1 (DMT1), transferrin receptor protein 1 (TfR1) and 2 (TfR2) and ZRT/IRT-like protein 14 (ZIP14) and faecal microbiota were assessed.ResultsIn DPBFE group, unlike in DPB and DFE groups, duodenal Fe content was higher compared to DD group. Similarly, serum Ft level was higher in DPBFE group, but not in DPB and DFE groups, compared to DD group.ConclusionsSix weeks simultaneous oral multistrain probiotic and Fe supplementation, but not exclusive probiotic or Fe intake, increases duodenal Fe absorption in rats and presents higher effectiveness in increasing tissue Fe stores.     

Iron absorption by Belgrade rat pups during lactation

Divalent metal transporter-1 (DMT1) mediates dietary nonheme iron absorption. Belgrade (b) rats have defective iron metabolism due to a mutation in the DMT1 gene. To examine the role of DMT1 in neonatal iron assimilation, b/b and b/+ pups were cross-fostered to F344 Fischer dams injected with (59)FeCl(3) twice weekly during lactation. Tissue distribution of the radioisotope in the pups was determined at weaning (day 21). The b/b pups had blood (59)Fe levels significantly lower than b/+ controls but significantly higher (59)Fe tissue levels in heart, bone marrow, skeletal muscle, kidney, liver, spleen, stomach, and intestines. To study the pharmacokinetics of nonheme iron absorption at the time of weaning, (59)FeCl(3) was administered to 21-day-old b/b and b/+ rats by intragastric gavage. Blood (59)Fe levels measured 5 min to 4 h postgavage were significantly lower in b/b rats, consistent with impaired DMT1 function in intestinal iron absorption. Tissue (59)Fe levels were also lower in b/b rats postgavage. Combined, these data suggest that DMT1 function is not essential for iron assimilation from milk during early development in the rat.     

Effects of stearic acid and beef tallow on iron utilization by the rat.

Two experiments were done in which anemic rats were fed diets containing safflower oil or stearic acid and low (10 ppm) or adequate (39-42 ppm) iron. Diets were 24% fat by weight. In the stearic acid diets, 2% (Experiment 1) or 4% (Experiment 2) of the fat was supplied by safflower oil to satisfy essential fatty acid requirements. Repletion of hemoglobin, hematocrit, and liver iron was assessed. Compared with safflower oil in both experiments, stearic acid had a significant positive effect (P less than 0.0001) on repletion of hemoglobin (Hb), hematocrit (Hct), and liver iron concentration; the effect on Hb and Hct was most pronounced when dietary iron was low. When expressed as g Hb/mg Fe intake, Hb repletion was affected by a significant interaction between fat and Fe (P less than 0.002) and was greatest in rats fed low iron stearic acid diets. In a third experiment, rats were fed low dietary iron and 24% safflower oil, 20% stearic acid + 4% safflower oil, 3.2% stearic acid + 20.8% safflower oil, or 20% beef tallow + 4% safflower oil. The 20% beef tallow provided 3.2% stearic acid in the total diet. The response of Hb and Hct were similar to those in the first two experiments for rats fed safflower oil or stearic acid. Rats fed beef tallow had significantly greater (P less than 0.05) Hb and Hct repletion than did rats fed safflower oil, although the degree of repletion was less than that observed in rats fed 20% stearic acid. There was no difference in iron repletion of rats fed 3.2% stearic acid and rats fed beef tallow. We conclude that stearic acid enhances iron utilization by rats.     

Iron absorption and distribution in TNFΔARE/+ mice,a model of chronic inflammation

Hemizygous TNF^ΔARE/+ mice are a murine model for chronic inflammation. We utilized these animals to study iron-kinetics and corresponding protein expression in an iron-deficient and iron-adequate setting. ⁵⁹Fe-absorption was determined in ligated duodenal loops in vivo. Whole body distribution of i.v. injected ⁵⁹Fe was analysed, and the organ specific expression of ferroportin, transferrin receptor-1, hepcidin and duodenal DMT-1 was quantified by real-time PCR and Western blotting.Duodenal ⁵⁹Fe-lumen-to-body transport was not affected by the genotype. Duodenal ⁵⁹Fe-retention was increased in TNF^ΔARE/+ mice, suggesting higher ⁵⁹Fe-losses with defoliated enterocytes. Iron-deficiency increased duodenal ⁵⁹Fe-lumen-to-body transport, and higher duodenal ⁵⁹Fe-tissue retention went along with higher duodenal DMT-1, ferroportin, and liver hepcidin expression. TNF^ΔARE/+ mice significantly increase their ⁵⁹Fe-content in inflamed joints and ilea, and correspondingly reduce splenic ⁵⁹Fe-content. Leukocyte infiltrations in the joints suggest a substantial shift of iron-loaded RES cells to inflamed tissues as the underlying mechanism. This finding was paralleled by increased non-haem iron content in joints and reduced haemoglobin and haematocrit concentrations in TNF^ΔARE/+ mice.In conclusion, erythropoiesis in inflamed TNF^ΔARE/+ mice could be iron-limited due to losses with exfoliated iron-loaded enterocytes and/or to increased iron-retention in RES cells that shift from the spleen to inflamed tissues.     

Iron requirements

Absorbed iron (Fe) requirements are partly recalculated based on new figures for Fe requirements in menstruating women. The new higher figures were obtained by including in the calculation of the total requirements the effect of variations in hemoglobin concentration, which influences the variation in menstrual Fe losses and the variation in basal Fe losses. Higher figures were also found for menstruating teenage girls. Dietary iron requirements were also recalculated based on a critical examination of data available allowing estimations of bioavailability of the dietary iron in Western-type diets. In borderline Fe-deficient subjects, with optimal hemoglobin levels but no iron stores, the 95th percentile range for the bioavailability was estimated to 14–16% of the fraction of the dietary Fe that is potentially available for absorption (correction for partially available fortification Fe).