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

Ting Yun Chang, Kai Li Liu, Cheng Sheng Chang, Chien Tien Su, Seu Hwa Chen, Yu Chieh Lee, Jung Su Chang

Research output: Contribution to journalArticle

4 Citations (Scopus)

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.

Original languageEnglish
JournalMolecular Nutrition and Food Research
DOIs
Publication statusAccepted/In press - Jan 1 2018

Fingerprint

Cell Aggregation
High Fat Diet
high fat diet
citrates
hemoglobin
Hemoglobins
macrophages
obesity
erythrocytes
Iron
Obesity
Erythrocytes
animal models
Macrophages
iron
metabolism
heme oxygenase (biliverdin-producing)
heme iron
rats
Heme Oxygenase-1

Keywords

  • CD163+ macrophages
  • Free hemoglobin
  • High-fat diet
  • Iron supplementation
  • Red-blood-cell aggregation

ASJC Scopus subject areas

  • Biotechnology
  • Food Science

Cite this

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title = "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",
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",
author = "Chang, {Ting Yun} and Liu, {Kai Li} and Chang, {Cheng Sheng} and Su, {Chien Tien} and Chen, {Seu Hwa} and Lee, {Yu Chieh} and Chang, {Jung Su}",
year = "2018",
month = "1",
day = "1",
doi = "10.1002/mnfr.201700442",
language = "English",
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TY - JOUR

T1 - 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

AU - Chang, Ting Yun

AU - Liu, Kai Li

AU - Chang, Cheng Sheng

AU - Su, Chien Tien

AU - Chen, Seu Hwa

AU - Lee, Yu Chieh

AU - Chang, Jung Su

PY - 2018/1/1

Y1 - 2018/1/1

N2 - 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.

AB - 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.

KW - CD163+ macrophages

KW - Free hemoglobin

KW - High-fat diet

KW - Iron supplementation

KW - Red-blood-cell aggregation

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