Plasma hepcidin level is elevated by water immersion-induced central fatigue via hepatic inflammatory response in male and female rats.

Fatigue is a subjective phenomenon caused by physical or mental overexertion; however, its objective biomarkers specific to the types of fatigue remain unclear. Here, we examined whether plasma hepcidin levels, which are regulated by inflammation or iron metabolism, are elevated by peripheral and central fatigue in male and female rats. Eight-week-old Wistar rats were divided into three groups: peripheral fatigue, central fatigue, and sedentary control groups. Peripheral fatigue was induced by moderate-intensity aerobic treadmill running, and central fatigue was induced by keeping rats in a cage flooded with water to a 2.5 cm depth for 5 days. Although both male and female rats showed similar behavioral phenotypes in peripheral and central fatigue groups, plasma hepcidin levels after fatigue induction were significantly elevated only in the central fatigue group. While neither iron panels nor tissue non-heme iron levels corresponded to changes in plasma hepcidin, levels of phospho-STAT3 at Tyr(705) in the liver were significantly elevated in both sexes in the central fatigue group, suggesting the presence of hepatic inflammation that can lead to hepcidin upregulation. The collective findings indicate that elevation of plasma hepcidin level may be a promising biomarker for central fatigue, but not for peripheral fatigue, regardless of iron metabolism alteration.