Karaushi Takuro, Ogawa Toshifumi, Fusagawa Hiroyori, Kudo Taiki, Inoue Yuito, Yamada Takashi, Ichise Nobutoshi, Sato Tatsuya, Tohse Noritsugu
Department of Cellular Physiology and Signal Transduction, Sapporo Medical University School of Medicine, Sapporo, Japan.
Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan.
Physiol Rep. 2025 Aug;13(15):e70468. doi: 10.14814/phy2.70468.
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.
疲劳是一种由身体或精神过度劳累引起的主观现象；然而，针对不同类型疲劳的客观生物标志物仍不明确。在此，我们研究了受炎症或铁代谢调节的血浆铁调素水平是否会因雄性和雌性大鼠的外周和中枢疲劳而升高。将8周龄的Wistar大鼠分为三组：外周疲劳组、中枢疲劳组和久坐对照组。通过中等强度的有氧跑步机跑步诱导外周疲劳，通过将大鼠置于水深2.5厘米的笼子中5天来诱导中枢疲劳。尽管雄性和雌性大鼠在外周和中枢疲劳组中表现出相似的行为表型，但疲劳诱导后血浆铁调素水平仅在中枢疲劳组中显著升高。虽然铁指标和组织非血红素铁水平均与血浆铁调素的变化不相关，但中枢疲劳组中两性肝脏中Tyr(705)位点的磷酸化STAT3水平均显著升高，提示存在可导致铁调素上调的肝脏炎症。总体研究结果表明，无论铁代谢是否改变，血浆铁调素水平升高可能是中枢疲劳的一个有前景的生物标志物，但不是外周疲劳的生物标志物。
