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High-fat diet causes iron deficiency via hepcidin-independent reduction of duodenal iron absorption.
J Nutr Biochem. 2012 Dec; 23(12):1600-8.JN

Abstract

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.

Authors+Show Affiliations

Department of Internal Medicine I, Medical University Innsbruck, Innsbruck, Austria.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22444869

Citation

Sonnweber, Thomas, et al. "High-fat Diet Causes Iron Deficiency Via Hepcidin-independent Reduction of Duodenal Iron Absorption." The Journal of Nutritional Biochemistry, vol. 23, no. 12, 2012, pp. 1600-8.
Sonnweber T, Ress C, Nairz M, et al. High-fat diet causes iron deficiency via hepcidin-independent reduction of duodenal iron absorption. J Nutr Biochem. 2012;23(12):1600-8.
Sonnweber, T., Ress, C., Nairz, M., Theurl, I., Schroll, A., Murphy, A. T., Wroblewski, V., Witcher, D. R., Moser, P., Ebenbichler, C. F., Kaser, S., & Weiss, G. (2012). High-fat diet causes iron deficiency via hepcidin-independent reduction of duodenal iron absorption. The Journal of Nutritional Biochemistry, 23(12), 1600-8. https://doi.org/10.1016/j.jnutbio.2011.10.013
Sonnweber T, et al. High-fat Diet Causes Iron Deficiency Via Hepcidin-independent Reduction of Duodenal Iron Absorption. J Nutr Biochem. 2012;23(12):1600-8. PubMed PMID: 22444869.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - High-fat diet causes iron deficiency via hepcidin-independent reduction of duodenal iron absorption. AU - Sonnweber,Thomas, AU - Ress,Claudia, AU - Nairz,Manfred, AU - Theurl,Igor, AU - Schroll,Andrea, AU - Murphy,Anthony T, AU - Wroblewski,Victor, AU - Witcher,Derrick R, AU - Moser,Patrizia, AU - Ebenbichler,Christoph F, AU - Kaser,Susanne, AU - Weiss,Günter, Y1 - 2012/03/23/ PY - 2011/06/06/received PY - 2011/10/18/revised PY - 2011/10/31/accepted PY - 2012/3/27/entrez PY - 2012/3/27/pubmed PY - 2013/5/1/medline SP - 1600 EP - 8 JF - The Journal of nutritional biochemistry JO - J Nutr Biochem VL - 23 IS - 12 N2 - 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. SN - 1873-4847 UR - https://www.unboundmedicine.com/medline/citation/22444869/High_fat_diet_causes_iron_deficiency_via_hepcidin_independent_reduction_of_duodenal_iron_absorption_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0955-2863(11)00308-1 DB - PRIME DP - Unbound Medicine ER -