Regulation Of Intestinal Iron Absorption Research Articles

Expression of genes involved in iron metabolism in mouse intestine.

Intestinal nonheme iron levels and mRNA levels of genes implicated in iron metabolism were measured in mice with altered iron metabolism [chronic (4 wk) and acute (4 days) dietary iron deficiency; iron overload and hypoxia] to investigate their role in the process and regulation of intestinal iron absorption. Mucosal nonheme iron levels were decreased by both chronic and acute iron deficiency and increased by iron overload but were not affected by hypoxia. There was evidence of a gradient of mucosal nonheme iron along the small intestine (duodenum, jejunum > ileum). There were also regional differences in H-ferritin (duodenum > ileum) and transferrin receptor (ileum > duodenum) mRNA levels. Iron overload produced a decrease in transferrin receptor (TfR) mRNA in the duodenum, with ferritin mRNA levels unaffected in both the duodenum and ileum. Chronic iron deficiency induced a twofold increase in TfR mRNA levels in both the duodenum and ileum, whereas H- and L-ferritin mRNA levels did not change significantly. The ratio of H- to L-ferritin mRNA decreased significantly during exposure to hypoxia; however, individual ferritin and TfR mRNA levels were not significantly altered. Calreticulin (mobilferrin), cysteine-rich intestinal protein, and H(+)-adenosinetriphosphatase mRNA levels were virtually unchanged in all models. A comparison with previously published data on changes in iron absorption leads us to conclude that 1) iron absorption can be altered independently of effects on transcripts of genes for iron-related proteins, and 2) it is not essential for iron absorption to be coordinated with regulation of mucosal iron metabolism.

Duodenal expression of NF‐E2 in mouse models of altered iron metabolism

This study investigated the relationship between duodenal mucosal mRNA levels of the transcription factor, NF-E2, H-ferritin (a putative NF-E2 regulated gene) and iron absorption in mice. CD1-strain mice with normal and altered iron metabolism (hypoxic, iron-deficient, iron-loaded) and animals with genetic defects of iron metabolism (hypotransferrinaemia, beta-thalassaemia) were studied. Tissue RNA from these mouse models was subjected to reverse transcription and PCR amplification for NF-E2 and a stable ribosomal protein (S14) and the products analysed with an automated laser fluorescent sequencer. Duodenal NF-E2 mRNA levels were generally low and decreased in the hypoxic and iron-deficient groups, both of which exhibited elevated iron absorption as compared to controls. A modest increase in the NF-E2 mRNA level was seen in the iron-loaded mice, whose iron absorption was decreased. In contrast, both the genetic strains showed elevated NF-E2 mRNA levels in conjunction with raised iron absorption values. Only the iron-deficient group exhibited an alteration in the duodenal mucosal H/L ferritin ratio. Hence, no relationship was evident between the NF-E2 mRNA levels and the H/L ferritin ratio. These data indicate that NF-E2 is not the primary regulator of intestinal iron absorption.

Mechanisms and regulation of intestinal iron absorption.

Mechanisms and regulation of intestinal iron absorption.

Intestinal iron absorption and mucosal transferrin in rats subjected to hypoxia.

Three days hypoxia (0.5 atm) increased the haemoglobin and haematocrit values in rats paralleled by enhanced intestinal iron absorption. The destination of recently-absorbed iron was primarily the erythropoietic system, viz. bone marrow, spleen and red cells. Total plasma transferrin, was increased by 30%, but no significant changes in mucosal transferrin were found. No increase in labelling of mucosal transferrin by absorbed iron was observed. These results suggest that mucosal transferrin does not play a major role in the regulation of intestinal iron absorption in hypoxia.

HEME IRON RELATIVE TO TOTAL DIETARY INTAKES OF IRON — REVIEW

ABSTRACTIron deficiency is a common nutritional anomaly encountered in surveys in diverse populations throughout the world. Etiological factors, including gastrointestinal disorders such as gastric ulcers or ulcerative colitis have a significant effect on and may cause this nutritional disorder.Research has indicated that dietary iron is found predominantly as either heme (absorbable) iron or as nonheme (less readily absorbable) iron. The absorption of nonheme iron is enhanced by the presence, in the diet, of certain factors, mainly ascorbic acid and meat, fish or poultry. Certain inhibitors and their effects have also been identified.Understanding the mechanism and regulation of intestinal iron absorption and the relationship to absorbable iron versus total iron intakes is of importance. This paper includes a review of the following information: food sources of both types of iron; factors affecting absorption — enhancers and inhibitors; and physiological states affecting iron absorption. Meats serve as a source of heme iron as well as having a promoting effect on absorption of nonheme iron.

Homeostatic Mechanisms in the Utilization of Exogenous Iron in Children Recovering from Severe Malnutrition

We evaluated the role of initial iron stores on iron accumulation during recovery from severe edematous protein‐energy malnutrition in children. Twenty‐six preschool children were divided in two groups according to their initial iron reserves, as estimated from serum ferritin concentration, using a cutoff criterion of 30 ng/ml. The low ferritin (LF) group had a mean serum ferritin level of 12 ± 8 ng/dl, and the high ferritin (HF) group, 86 ± 32 ng/dl. Both groups had similar degrees of malnutrition and of anemia, as defined by hemoglobin concentration. All children received an adequate therapeutic diet and 60 mg iron daily as ferrous sulfate. The recovery of biochemical and anthropometric indicators of nutritional status, as well as of hemoglobin concentration, was similar in both groups. On the contrary, the LF group showed a marked increase in serum ferritin concentration from the onset of treatment, whereas the HF group had a net decline in this parameter by 30 days, and a stable level thereafter. The difference in serum ferritin concentration between groups was maintained until day 60, and both groups ended the study (90 days) with similar levels. Estimation of the utilization of exogenous iron from changes in total‐body iron during the first 60 days of recovery showed the LF group to retain an average of 9.3% of iron intake, whereas the HF group retained only 1.4%. These results confirm that similar degrees of anemia in severe malnutrition can be associated with markedly different iron reserves, and suggest that the homeostatic regulation of intestinal iron absorption by the storage iron pool may produce a lower utilization of oral iron supplements in malnourished children with high iron reserves at the onset of treatment.