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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\u2010week\u2010old Wistar rats were divided into three groups: peripheral fatigue, central fatigue, and sedentary control groups. Peripheral fatigue was induced by moderate\u2010intensity aerobic treadmill running, and central fatigue was induced by keeping rats in a cage flooded with water to a 2.5\u2009cm depth for 5\u2009days. 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\u2010heme iron levels corresponded to changes in plasma hepcidin, levels of phospho\u2010STAT3 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.<\/jats:p>","DOI":"10.14814\/phy2.70468","type":"journal-article","created":{"date-parts":[[2025,8,4]],"date-time":"2025-08-04T12:24:19Z","timestamp":1754310259000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Plasma hepcidin level is elevated by water immersion\u2010induced central fatigue via hepatic inflammatory response in male and female rats"],"prefix":"10.14814","volume":"13","author":[{"given":"Takuro","family":"Karaushi","sequence":"first","affiliation":[{"name":"Department of Cellular Physiology and Signal Transduction Sapporo Medical University School of Medicine  Sapporo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toshifumi","family":"Ogawa","sequence":"additional","affiliation":[{"name":"Department of Cellular Physiology and Signal Transduction Sapporo Medical University School of Medicine  Sapporo Japan"},{"name":"Department of Cardiovascular, Renal and Metabolic Medicine Sapporo Medical University School of Medicine  Sapporo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroyori","family":"Fusagawa","sequence":"additional","affiliation":[{"name":"Department of Cellular Physiology and Signal Transduction Sapporo Medical University School of Medicine  Sapporo Japan"},{"name":"Department of Orthopedic Surgery Sapporo Medical University School of Medicine  Sapporo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Taiki","family":"Kudo","sequence":"additional","affiliation":[{"name":"Department of Cellular Physiology and Signal Transduction Sapporo Medical University School of Medicine  Sapporo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuito","family":"Inoue","sequence":"additional","affiliation":[{"name":"Department of Cellular Physiology and Signal Transduction Sapporo Medical University School of Medicine  Sapporo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takashi","family":"Yamada","sequence":"additional","affiliation":[{"name":"Graduate School of Health Sciences Sapporo Medical University  Sapporo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nobutoshi","family":"Ichise","sequence":"additional","affiliation":[{"name":"Department of Cellular Physiology and Signal Transduction Sapporo Medical University School of Medicine  Sapporo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7876-1772","authenticated-orcid":false,"given":"Tatsuya","family":"Sato","sequence":"additional","affiliation":[{"name":"Department of Cellular Physiology and Signal Transduction Sapporo Medical University School of Medicine  Sapporo Japan"},{"name":"Department of Cardiovascular, Renal and Metabolic Medicine Sapporo Medical University School of Medicine  Sapporo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Noritsugu","family":"Tohse","sequence":"additional","affiliation":[{"name":"Department of Cellular Physiology and Signal Transduction Sapporo Medical University School of Medicine  Sapporo Japan"},{"name":"Department of Health and Nutrition, Faculty of Human Sciences Hokkaido Bunkyo University  Eniwa Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,8,4]]},"reference":[{"doi-asserted-by":"publisher","key":"e_1_2_12_2_1","DOI":"10.1038\/s41598-024-73049-9"},{"doi-asserted-by":"publisher","key":"e_1_2_12_3_1","DOI":"10.2147\/RMHP.S444900"},{"doi-asserted-by":"publisher","key":"e_1_2_12_4_1","DOI":"10.3389\/fnetp.2021.794392"},{"doi-asserted-by":"publisher","key":"e_1_2_12_5_1","DOI":"10.1136\/gutjnl-2011-300304"},{"doi-asserted-by":"publisher","key":"e_1_2_12_6_1","DOI":"10.4049\/jimmunol.2001022"},{"doi-asserted-by":"publisher","key":"e_1_2_12_7_1","DOI":"10.1093\/cvr\/cvq076"},{"key":"e_1_2_12_8_1","first-page":"H880","article-title":"Effects of chronic stress on rat heart function following regional ischemia: A sex\u2010dependent investigation","volume":"327","author":"Cairns M.","year":"2024","journal-title":"American Journal of Physiology. 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