Gladys O Latunde-Dada, PhD, Lecturer, Faculty of Life Sciences and Medicine, Division of Diabetes and Nutritional Sciences, King’s College London, Franklin Wilkins Building, 150 Stanford Street, London SE1 9NH, United Kingdom. yemisi.latunde-dada@kcl.ac.uk
Research Domain of This Article
Hematology
Article-Type of This Article
Basic Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Hematol. Feb 6, 2017; 6(1): 17-23 Published online Feb 6, 2017. doi: 10.5315/wjh.v6.i1.17
Intestinal heme absorption in hemochromatosis gene knock-out mice
Abas H Laftah, Robert J Simpson, Gladys O Latunde-Dada
Abas H Laftah, Vascular Sciences, NHLI, Imperial Centre for Translational and Experimental Medicine, Imperial College London, London W12 0NN, United Kingdom
Robert J Simpson, Gladys O Latunde-Dada, Faculty of Life Sciences and Medicine, Division of Diabetes and Nutritional Sciences, King’s College London, London SE1 9NH, United Kingdom
Author contributions: All the authors contributed to the manuscript.
Institutional review board statement: The study was reviewed and approved by King’s College London, Diabetes and Nutritional Sciences Division Institutional Review Board.
Institutional animal care and use committee statement: All procedures involving animals were approved by the Animal care and the regulation of scientific procedures met the criteria laid down by the United Kingdom “Animals (Scientific Procedures) Act 1986”.
Conflict-of-interest statement: Laftah AH, Simpson RJ and Latunde-Dada GO declare no conflict of interest.
Data sharing statement: Technical appendix, statistical analysis and dataset are available from the corresponding author at yemisi.latunde-dada@kcl.ac.uk. All authors gave informed consent for data sharing.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Gladys O Latunde-Dada, PhD, Lecturer, Faculty of Life Sciences and Medicine, Division of Diabetes and Nutritional Sciences, King’s College London, Franklin Wilkins Building, 150 Stanford Street, London SE1 9NH, United Kingdom. yemisi.latunde-dada@kcl.ac.uk
Telephone: +44-20-88484256 Fax: +44-20-88484500
Received: August 29, 2016 Peer-review started: September 1, 2016 First decision: October 26, 2016 Revised: November 18, 2016 Accepted: December 16, 2016 Article in press: December 19, 2016 Published online: February 6, 2017 Processing time: 143 Days and 5.7 Hours
Abstract
AIM
To investigat the influence of hemochromatosis gene (Hfe) mutation on 59Fe labelled duodenal heme absorption in mice.
METHODS
Heme absorption was measured in Hfe wild type and Hfe(-/-) mice by the duodenal tied loop and by oral gavage methods. The mRNA expression of heme oxygenase (HO-1), Abcg2 and Flvcr1 genes and levels were determined by quantitative polymerase chain reaction.
RESULTS
Heme absorption was significantly increased in homozygous Hfe(-/-) mice despite significant hepatic and splenic iron overload. While duodenal HO-1 mRNA was highly expressed in the wild type and Hfe(-/-) heme-treated group following 24 h heme administration, Flvcr1a mRNA decreased. However, Abcg2 mRNA expression levels in duodenum remained unchanged.
CONCLUSION
Heme absorption was enhanced in Hfe(-/-) mice from both duodenal tied-loop segments and by oral gavage methods. HO-1 mRNA levels were enhanced in mice duodenum after 24 h of heme feeding and may account for enhanced heme absorption in Hfe(-/-) mice. Implications for dietary recommendations on heme intake by Hfe subjects to modulate iron loading are important clinical considerations.
Core tip: These results indicate that loss of hemochromatosis gene (Hfe) protein results in increased dietary heme iron absorption that further contributes to the iron loading of the liver and other tissues of mice. Enhanced heme iron intake by homozygous Hfe subjects may contribute to body iron overload and early manifestation of phenotypic traits. This may have implications for dietary recommendations on heme intake by hemochromatosis subjects to avert tissue iron loading.
