High-Altitude Acclimatization Suppresses Hepcidin Expression During Severe Energy Deficit

Hennigar, Stephen R.; Berryman, Claire E.; Kelley, Alyssa M.; Anderson, Bradley J.; Young, Andrew; McClung, James P.; Pasiakos, Stefan M.

doi:10.1089/ham.2019.0109

Cited by 6 publications

(7 citation statements)

References 26 publications

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“…Based on our findings, we, therefore, speculate that the reduction of sFER was related to altitude per se as a middle-term response to hypoxia regardless of ethnic origin. As reported in other studies, this reduction is related to an increased iron demand for the erythropoiesis and to a make up for adaptive changes due to hypoxia such as increased intestinal iron uptake, augmentation of serum iron-binding capacity, and enhanced mobilization of iron from cellular stores (Goetze et al, 2013;Hennigar et al, 2020).…”

Section: Discussionsupporting

confidence: 55%

Serum ferritin and vitamin D evaluation in response to high altitude comparing Italians trekkers vs Nepalese porters

Magliulo

Bondi

Pietrangelo

et al. 2020

European Journal of Sport Science

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Altitude hypoxia induces changes in iron homeostasis with serum ferritin (sFER) response being recently linked to erythropoiesis. The main aim of this study was to investigate sFER and Vitamin D (Vit D) response to hypobaric hypoxia, taking into account factors including nutrition and ethnic origin. As part of a "Kanchenjunga Exploration & Physiology" project, 6 Italian trekkers and 6 Nepalese porters took part in a 19-days long altitude trek in the Himalayas self-recording daily food consumption. Blood samples were collected and analyzed before and after the trek for sFER and Vit D. A webbased system calculated the dietary intake, generating reports that were used for later statistical analyses. sFER decreased after the trek (on average by 26% p = 0.013, partial η 2 = 0.479) in both groups, whereas Vit D did not change in both groups. Nepalese tended to have lower sFER, but this difference was reduced when corrected for the dietary intake. Mean Cell Volume (MCV) and Hematocrit (HCT), in respect to baseline, remained higher 10 days after the trek (respectively, 87.37-88.85 fL with p = 0.044, and 43.05-44.63% with p = 0.065) in Italian trekkers. The observed reduction of sFER levels was related to altitude per se as inflammation or anemia were medically excluded. sFER, therefore, may act as a primary factor in the examination of hypobaric hypoxia in field studies. The results of this study open a new door into the mechanisms of iron homeostasis in specific tissues related to hypoxia adaptations, taking into account dietary intake and ethnic origin.

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Section: Discussionsupporting

confidence: 55%

Serum ferritin and vitamin D evaluation in response to high altitude comparing Italians trekkers vs Nepalese porters

Magliulo

Bondi

Pietrangelo

et al. 2020

European Journal of Sport Science

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“…Excess hepcidin degrades the ferroportin export channels on the surface of macrophages and the intestinal duodenum, resulting in reduced iron recycling and absorption from the intestine (4,5). The relationships between increased hepcidin levels and risk of iron deficiency have been investigated in various health settings, and hepcidin has been suggested as a surrogate marker for iron metabolism in athletes (4)(5)(6)(7)(8)(9).…”

Section: Introductionmentioning

confidence: 99%

“…Excessive exercise increases the risk of iron deficiency (3), and multiple studies have attempted to clarify the relationship between blood levels of hepcidin and energy availability (7)(8)(9)(10). The appetite-related hormone leptin is a well-known adipokine (11,12) reported to stimulate hepcidin production in mice and cultured cells (13,14).…”

Section: Introductionmentioning

confidence: 99%

Comparisons Between Serum Levels of Hepcidin and Leptin in Male College-Level Endurance Runners and Sprinters

et al. 2021

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Background: Hepcidin-25 is a 25 amino acid hepatokine and a key regulator of iron metabolism related to iron deficiency anemia. Recent studies have suggested that an elevated hepcidin level is correlated with low energy availability. Leptin is an appetite-suppressing adipokine and has been reported to stimulate hepcidin production in animals and cultured cells. While leptin is modulated by exercise, it is known that endurance runners and sprinters practice different types of exercise. This study investigated and compared the relationships between hepcidin and leptin levels, iron status, and body fat to understand better the risk of iron deficiency anemia in endurance runners and sprinters.Methods: Thirty-six male college track and field athletes (15 endurance runners and 21 sprinters) were recruited for this study. Dietary intake, body composition, and blood levels of ferritin, hepcidin-25, leptin, and adiponectin were measured. Correlations between hepcidin levels and ferritin, body fat, leptin, and adiponectin were evaluated using Pearson's correlation coefficient for each group.Results: The endurance runners had lower hepcidin levels and higher leptin and adiponectin levels compared with sprinters. Ferritin was positively correlated with hepcidin-25 levels in both the endurance and sprinter groups. A positive correlation was observed between hepcidin-25 and body fat or leptin levels only in sprinters.Conclusion: This is the first study investigating the relationship between blood levels of hepcidin and leptin in athletes. The positive correlation between hepcidin-25 and leptin was observed in sprinters but not endurance runners.

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“…Less established, but still important to mention, is also the debate surrounding the issue of hypoxia/hypoxemia and certain symptoms resembling, but differentiable from, altitude illness [ 8 , 9 , 15 , 54 ]. Congruously, hepcidin expression levels have also been investigated in the context of high-altitude acclimatization [ 59 ] (see also ref. [ 27 ]).…”

Section: Resultsmentioning

confidence: 99%

COVID-19 and iron dysregulation: distant sequence similarity between hepcidin and the novel coronavirus spike glycoprotein

Ehsani

2020

Biol Direct

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The spike glycoprotein of the SARS-CoV-2 virus, which causes COVID-19, has attracted attention for its vaccine potential and binding capacity to host cell surface receptors. Much of this research focus has centered on the ectodomain of the spike protein. The ectodomain is anchored to a transmembrane region, followed by a cytoplasmic tail. Here we report a distant sequence similarity between the cysteine-rich cytoplasmic tail of the coronavirus spike protein and the hepcidin protein that is found in humans and other vertebrates. Hepcidin is thought to be the key regulator of iron metabolism in humans through its inhibition of the iron-exporting protein ferroportin. An implication of this preliminary observation is to suggest a potential route of investigation in the coronavirus research field making use of an already-established literature on the interplay of local and systemic iron regulation, cytokine-mediated inflammatory processes, respiratory infections and the hepcidin protein. The question of possible homology and an evolutionary connection between the viral spike protein and hepcidin is not assessed in this report, but some scenarios for its study are discussed.

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High-Altitude Acclimatization Suppresses Hepcidin Expression During Severe Energy Deficit

Cited by 6 publications

References 26 publications

Serum ferritin and vitamin D evaluation in response to high altitude comparing Italians trekkers vs Nepalese porters

Serum ferritin and vitamin D evaluation in response to high altitude comparing Italians trekkers vs Nepalese porters

Comparisons Between Serum Levels of Hepcidin and Leptin in Male College-Level Endurance Runners and Sprinters

COVID-19 and iron dysregulation: distant sequence similarity between hepcidin and the novel coronavirus spike glycoprotein

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