Prolonged High Altitude Exposure Results in Elevated Erythroferrone and Diminished Hepcidin Levels in Healthy Young Male Volunteers
Abstract
Iron, an essential micronutrient, supports physical and cognitive performance through the binding of proteins and enzymes involved in oxygen transport and energy metabolism. High altitude (HA) acclimatization affects iron metabolism and results in increased hemoglobin concentrations due to hypoxia‐stimulated hemoconcentration and erythropoeisis. Iron homeostasis is regulated by hepcidin, aprotein affecting iron absorption and metabolism through the binding and degradation of ferroportin, the primary cellular iron exporter. Erythroferrone, a recently identified hormone, inhibits hepcidin transcription during erythropoiesis in animal models. As hepcidin and erythroferrone have not been assessed in human volunteers exposed to HA, the primary objective of the present study was to explore the effects of HA on hepcidin, erythroferrone, andiron availability. Hemoglobin, hepcidin, erythroferrone, and serum iron were measured in unacclimatized healthy youngmen (n = 17, age [mean ± SD] = 23.4 ± 5.6 yrs, body weight = 81.9 ± 13.9 kg) residing at sea level(SL) and HA (19 d, 4300 m). While residing at HA, volunteers consumed energy restricted diets providing 70% of SL weight maintenance energy needs, and engaged in prescribed physical activity to induce a 40% total daily energy deficit. As compared to SL, HA resulted in increased hemoglobin (16.6 ± 0.9 vs. 14.3 ± 0.8 g/dL, P <0.01), diminished hepcidin (4.8± 3.4 vs. 7.5 ± 3.4 ng/mL, P <0.05), and increased erythroferrone (3.1 ± 2.1 vs. 0.9 ± 0.6pg/mL, P < 0.01). Serum iron increased at HA as compared to SL (104.7 ± 34.2 vs. 65.4 ± 17.4μg/mL, P < 0.01). Taken together, these data indicate that prolonged HA exposure in humans results in elevated erythroferrone, which is associated with suppressed hepcidin transcription and increased iron availability.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Apr 01, 2017
- Source ID
- 10.1096/fasebj.31.1_supplement.637.2
Entities
People
- Andrew J Young
- Claire E Berryman
- James P. Mcclung
- Stefan M. Pasiakos
- Stephen R Hennigar
Organizations
- United States Army Medical Research and Development Command
- United States Army Research Institute of Environmental Medicine