Format

Send to

Choose Destination
Mol Nutr Food Res. 2018 Jan;62(2). doi: 10.1002/mnfr.201700442. Epub 2017 Dec 29.

Ferric Citrate Supplementation Reduces Red-Blood-Cell Aggregation and Improves CD163+ Macrophage-Mediated Hemoglobin Metabolism in a Rat Model of High-Fat-Diet-Induced Obesity.

Author information

1
School of Nutrition and Health Sciences, College of Nutrition, Taipei Medical University, Taipei, Taiwan.
2
Department of Nutrition, Chung Shan Medical University, Taichung, Taiwan.
3
Department of Dietitian, Chung Shan Medical University Hospital, Taichung, Taiwan.
4
Department of Family Medicine, Taipei Medical University Hospital, Taipei, Taiwan.
5
School of Public Health, College of Public Health, Taipei Medical University, Taipei, Taiwan.
6
Department of Anatomy and Cell Biology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
7
Department of Obstetrics and Gynecology, Taipei Medical University Hospital, Taipei, Taiwan.
8
Nutrition Research Center, Taipei Medical University Hospital, Taipei, Taiwan.
9
Graduate Institute of Metabolism and Obesity Sciences, College of Nutrition, Taipei Medical University, Taipei, Taiwan.

Abstract

SCOPE:

In adults, >90% of the daily iron requirement is derived from macrophage-mediated heme iron, recycling from senescent red blood cells (RBCs) or free hemoglobin (Hb). Currently, the effects of pharmacological doses of iron supplementation on RBCs and heme iron recycling in obesity are unclear.

METHODS AND RESULTS:

Sprague Dawley rats are fed a standard diet or a 50% high-fat diet (HFD) with (0.25, 1, and 2 g of ferric iron per kg diet) or without ferric citrate supplementation for 12 weeks. Ferric iron increases hepatic iron accumulation in macrophages and hepatocyte-like cells. Compared with rats that received the standard diet, HFD-fed rats exhibit higher RBC aggregation and serum-free Hb levels but lower LVV-hemorphin-7 levels. These effects are reversed by ferric citrate supplementation. Immunofluorescent staining reveals that ferric iron increases the expression of hepatic CD163+ macrophages and heme oxygenase (HO)-1. A further analysis reveals the dose-related effects of ferric iron on hepatic globin degradation proteins (cathepsin D and glyoxalase 1), cytochrome p450 reductase expression, and HO-1 enzyme activity.

CONCLUSIONS:

Ferric citrate supplementation reduces RBC aggregation and improves CD163+ macrophage-mediated Hb metabolism in HFD-induced obese rats. These findings suggest that ferric citrate may be explored as an alternative treatment method for RBC dysfunction.

KEYWORDS:

CD163+ macrophages; free hemoglobin; high-fat diet; iron supplementation; red-blood-cell aggregation

PMID:
29064631
DOI:
10.1002/mnfr.201700442
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Wiley
Loading ...
Support Center