High-fat diet causes iron deficiency via hepcidin-independent reduction of duodenal iron absorption
Department of Internal Medicine I, Medical University Innsbruck, Innsbruck, Austria. The Journal of nutritional biochemistry
(Impact Factor: 3.79).
03/2012; 23(12). DOI: 10.1016/j.jnutbio.2011.10.013
Obesity is often associated with disorders of iron homeostasis; however, the underlying mechanisms are not fully understood. Hepcidin is a key regulator of iron metabolism and may be responsible for obesity-driven iron deficiency. Herein, we used an animal model of diet-induced obesity to study high-fat-diet-induced changes in iron homeostasis. C57BL/6 mice were fed a standard (SD) or high-fat diet (HFD) for 8 weeks, and in addition, half of the mice received high dietary iron (Fe+) for the last 2 weeks. Surprisingly, HFD led to systemic iron deficiency which was traced back to reduced duodenal iron absorption. The mRNA and protein expressions of the duodenal iron transporters Dmt1 and Tfr1 were significantly higher in HFD- than in SD-fed mice, indicating enterocyte iron deficiency, whereas the mRNA levels of the duodenal iron oxidoreductases Dcytb and hephaestin were lower in HFD-fed mice. Neither hepatic and adipose tissue nor serum hepcidin concentrations differed significantly between SD- and HFD-fed mice, whereas dietary iron supplementation resulted in increased hepatic hepcidin mRNA expression and serum hepcidin levels in SD as compared to HFD mice. Our study suggests that HFD results in iron deficiency which is neither due to intake of energy-dense nutrient poor food nor due to increased sequestration in the reticulo-endothelial system but is the consequence of diminished intestinal iron uptake. We found that impaired iron absorption is independent of hepcidin but rather results from reduced metal uptake into the mucosa and discordant oxidoreductases expressions despite enterocyte iron deficiency.
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- "Supplement users may have multiple disease-risk factors, including advanced age, obesity, and unbalanced diets rich in fat and sugars. Interestingly, a high-fat diet has been suggested to promote iron deficiency by reducing duodenal iron absorption and by inducing inflammation  . Although our mice were supplied with adequate dietary iron, curcumin supplementation markedly depleted iron stores in the presence of the Western-type diet (Fig. 3). "
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ABSTRACT: Curcumin has been shown to have many potentially health beneficial properties in vitro and in animal models with clinical studies on the toxicity of curcumin reporting no major side effects. However, curcumin may chelate dietary trace elements and could thus potentially exert adverse effects. Here, we investigated the effects of a 6 month dietary supplementation with 0.2% curcumin on iron, zinc, and copper status in C57BL/6J mice. Compared to non-supplemented control mice, we observed a significant reduction in iron, but not zinc and copper stores, in the liver and the spleen, as well as strongly suppressed liver hepcidin and ferritin expression in the curcumin-supplemented mice. The expression of the iron-importing transport proteins divalent metal transporter 1 and transferrin receptor 1 was induced, while hepatic and splenic inflammatory markers were not affected in the curcumin-fed mice. The mRNA expression of other putative target genes of curcumin, including the nuclear factor (erythroid-derived 2)-like 2 and haem oxygenase 1 did not differ between the groups. Most of the published animal trials with curcumin-feeding have not reported adverse effects on iron status or the spleen. However, it is possible that long-term curcumin supplementation and a Western-type diet may aggravate iron deficiency. Therefore, our findings show that further studies are needed to evaluate the effect of curcumin supplementation on iron status.
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- "It has been found that a high fructose diet impairs copper status and leads to iron overload . It has been shown that increased fat in the diet increases iron absorption , but there are also contradictory reports . It has been found that high-fructose diets induce copper deficiency, probably through impaired duodenum Ctr-1 expression, which leads to lower copper absorption [22, 25]. "
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ABSTRACT: The aim of this study was to assess the metabolic and physiological changes in rats fed a diet high in fat, fructose, and salt, and with excess iron level. Mineral status was also estimated. Wistar rats were assigned to groups fed either a standard control diet (C) or a diet high in fat, fructose, and salt. The noncontrol diets contained either normal (M) or high level (MFe) of iron. After 6 weeks, the length and weight of the rats were measured, and the animals were euthanized. The kidneys and gonads were collected, and blood samples were taken. Serum levels of insulin, nitric oxide, and iron were measured. The iron, zinc, copper, and calcium concentrations of tissues were determined. It was found that the M diet led to a significant increase in the relative kidney mass of the rats compared with the control group. Among the rats fed the M diet, markedly higher serum level of iron and lower levels of zinc and copper were observed in tissues, while significantly higher calcium levels were found in the gonads. The MFe diet resulted in decreased obesity index, insulin level, and nitric oxide serum concentration in the rats, when compared with both the M and C diets. The high iron level in the modified diet increased the relative mass of the gonads. The excess iron level in the diet disturbed the zinc, copper, and calcium status of tissues. The decrease in insulin and nitric oxide in rats fed the diet high in iron, fat, fructose, and salt was associated with disorders of zinc, copper, and calcium status, as well as with an increase in the relative mass of the gonads.
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ABSTRACT: Iron overload is a risk factor for diabetes. The link between iron and diabetes was first recognized in pathologic conditions-hereditary hemochromatosis and thalassemia-but high levels of dietary iron also impart diabetes risk. Iron plays a direct and causal role in diabetes pathogenesis mediated both by β cell failure and insulin resistance. Iron also regulates metabolism in most tissues involved in fuel homeostasis, with the adipocyte in particular serving an iron-sensing role. The underlying molecular mechanisms mediating these effects are numerous and incompletely understood but include oxidant stress and modulation of adipokines and intracellular signal transduction pathways.
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