LAUSR

Objectives In the US, prophylactic iron supplementation without thorough screening for iron deficiency is commonly practiced in both normal weight and low birth weight infants. In a nursing pig model, we previously found that excess dietary iron results in tissue iron overload, suggesting ineffective regulation of intestinal iron absorption. Herein, we aimed to determine if hepcidin-mediated ferroportin (FPN1) degradation is functionally immature in early life. Methods Twelve nursing piglets of normal birth weight (2.1 ± 0.4 kg, PD2) were supplemented with either low (AGAL, 1 mg/d·kg body weight) or high iron (AGAH, 15 mg/d·kg BW)) in form of ferrous sulfate solution. Eight low birth weight (1.2 ± 0.4 kg on PD2) piglets were supplemented with high iron (SGAH, 15 mg/d·kg BW) from PD2 to 21. All piglets were raised by suckling their sows. Blood samples were collected weekly for analysis of hemoglobin, hematocrit, and plasma iron. Duodenal mucosa (DM) and hepatic mRNA and protein expression of iron transporters and regulators were analyzed using RT-qPCR and Western blot. Data were analyzed using PROC MIXED of SAS with CONTRAST statement for planned comparison between AGAL and high iron groups. Results In comparison with AGAL, high iron, regardless of birth weight, significantly (P < 0.05) increased hemoglobin, transferrin saturation (74% vs. 49%), and plasma iron, and resulted in iron overload in DM and liver at PD21. Hepatic mRNA expression of HAMP and FTL in DM increased 275- and 3-fold, respectively, in response to high iron, whereas DMT1 in DM and TFRC in both liver and DM decreased by 7.4-, 3.8- and 5.3-fold, respectively. Consistently, protein expression of DMT1 in DM was lower in SGAH than that in AGAL; However, both mRNA and protein expression of FPN1 in DM and liver remained unaffected by iron provision or birth weight. Conclusions Hepcidin-induced ferroportin degradation is hypo-responsive to iron excess in a nursing pig model. Funding Sources UC Davis, NIFA.