HIF-2α could be a key regulator of Fe homeostasis in the gut of yellow-feathered broilers

This study examines the effects of age and dietary Fe on the duodenal and liver deposition of Fe, Cu, Mn, and Zn, and expression of genes involved in Fe homeostasis in yellow-feathered broilers. A total of 400 1-day-old male broilers were randomly assigned to 5 groups with different dietary Fe supplementation (0, 20, 80, 320, and 1280 mg/kg, from FeSO 4 •7H 2 O), and samples were collected at two time points (on d 21 and d 63). The basal diet for different growth stages contained 79.60, 72.64, and 61.79 mg/kg Fe, respectively. Each treatment contained 8 cages with 10 birds per cage. The ADG and ADFI at 21 and 63 d were reduced ( P ˂ 0.001) in broilers supplemented with 1280 mg/kg Fe compared to others, while FCR was not affected by treatment. Duodenal Cu ( P = 0.048) and hepatic Fe ( P = 0.015) deposition exhibited a treatment × age interaction, with both the lowest duodenal Cu and the highest hepatic Fe occurring with 1280 mg/kg of dietary Fe on d 63 ( P < 0.001). Dietary Fe supplementation decreased duodenal mucosal Mn concentrations ( P < 0.001) but did not change duodenal Zn or hepatic Zn. Higher duodenal Zn and Mn, and hepatic Mn, as well as lower hepatic Cu, were detected in birds on d 21 ( P < 0.05). There was an interaction of treatment × age on the expression of duodenal divalent metal transporter 1 ( DMT1 , P < 0.001) and hypoxia-inducible factor 1α ( HIF-1α , P = 0.007), with the expression of DMT1 at d 63 in birds supplemented with 0 or 20 mg/kg of Fe and the expression of HIF-1α at d 63 in birds supplemented with Fe higher than 21 d. Both ferroportin 1 (FPN1) and HIF-2α decreased with elevated dietary Fe supplementation ( P < 0.05). The expression of HIF-2α remained stable between ages ( P = 0.222). In conclusion, excess dietary Fe may trigger broiler Fe homeostasis via HIF-2α with weaker effects in juveniles.