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Early‐Life Iron Supplementation Alters Whole Body Iron Homeostasis, Serum Metabolites, and Social Novelty Discrimination in Pre‐Weanling Pigs
Author(s) -
Ji Peng,
McClorry Shan,
Lonnerdal Bo,
Slupsky Carolyn,
Kim Kwangwook,
Jinno Cynthia Nanako
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.436.7
Subject(s) - hemoglobin , hematocrit , ferroportin , anemia , weanling , serum iron , iron deficiency , iron deficiency anemia , total iron binding capacity , hepcidin , chemistry , ferrous , metabolism , medicine , endocrinology , organic chemistry
Iron supplementation is often practiced during infancy to prevent the potential risk of iron deficiency and iron deficiency anemia. However, the appropriate amount of iron supplementation is still debated. We used the neonatal pig as a preclinical model to investigate the impact of various doses and forms of iron supplementation on whole body iron homeostasis, systemic metabolism, and cognitive function during suckling. On PD 1, 24 crossbred piglets were stratified by sex and litter and randomly assigned to the following treatments: 1) no iron supplementation from PD 1 to 21 (IDE), 2) intramuscular injection of 100 mg elemental iron as iron dextran on PD 1 (IIN), 3) daily oral administration of 10 mg/kg BW elemental iron as FeSO 4 from PD 1 to 21 (IOL), or 4) daily oral administration of 50 mg/kg BW elemental iron as FeSO 4 from PD1 to 21 (IOH). Piglets were maternally fed in farrowing crates during the study. BW was measured daily, and blood was obtained by venipuncture on PD1, 7, 14 and 21 for analysis of hematocrit and hemoglobin. Additionally, 1 H‐NMR was used to assess the serum metabolome. Sociability was tested using a modified 3‐chamber arena on PD19 and 20. Tissues (liver, duodenum mucosa and brain regions) were sampled immediately after euthanasia on PD21 for analysis of tissue iron content and expression of genes encoding iron regulatory proteins. Treatment did not affect BW. In comparison with IDE, iron supplemented groups had significantly higher hematocrit on PD 7, 14, and 21, and hemoglobin on PD14 and 21. Iron supplementation increased brain iron content at PD21, but the difference was not significant between IDE and IOL. Liver iron was highest in IOH followed by IOL, and both were significantly higher than IDE and IIN. Iron supplementation decreased duodenal mucosal mRNA expression of DMT1/SLC11A2 and FPN/SLC40A1 , but increased hepatic expression of HAMP in a dose‐dependent manner. Iron supplementation significantly decreased hippocampal expression of TFRC , but there was no difference among iron supplemented groups. At PD 21, the serum metabolome indicated changes in energy metabolism, 1‐carbon metabolism, and oxidative stress, particularly between IDE and IOH. Pigs from all the groups exhibited normal social exploratory behavior. Intriguingly, pigs in the IOL and IOH groups displayed deficits in social novelty discrimination, which may result from alterations in short‐term memory processing. In conclusion, iron supplementation during the pre‐weaning period enhanced iron accumulation in both periphery and CNS, whereas a feedback mechanism to inhibit excess iron uptake was achieved, at least partially, through transcriptional modulation of iron regulatory proteins in gut, liver and brain. The underlying mechanism contributing to the deficit in social novelty discrimination warrants future study.