{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T15:13:53Z","timestamp":1783782833993,"version":"3.55.0"},"reference-count":66,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2024,3,1]],"date-time":"2024-03-01T00:00:00Z","timestamp":1709251200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32172808"],"award-info":[{"award-number":["32172808"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Nutrition Food Res"],"published-print":{"date-parts":[[2024,3]]},"abstract":"<jats:sec><jats:title>Scope<\/jats:title><jats:p>Oxidative stress caused by iron overload tends to result in intestinal mucosal barrier dysfunction and intestinal\u00a0microbiota\u00a0imbalance. As a neutral and nonprotein amino acid, L\u2010Citrulline (L\u2010cit) has been implicated in antioxidant and mitochondrial amelioration properties. This study investigates whether L\u2010cit can alleviate iron overload\u2010induced intestinal injury and explores the underlying mechanisms.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and results<\/jats:title><jats:p>C57BL\/6J mice are intraperitoneally injected with iron dextran, then gavaged with different dose of L\u2010cit for 2 weeks. L\u2010cit treatment significantly alleviates intestine pathological injury, oxidative stress, ATP level, and mitochondrial respiratory chain complex activities, accompanied by ameliorating mitochondrial quality control. L\u2010cit\u2010mediated protection is associated with the upregulation of Glutathione Peroxidase 4 (GPX4) expression, inhibition Nuclear Receptor Coactivator 4 (NCOA4)\u2010mediated ferritinophagy and ferroptosis, and improvement of gut microbiota. To investigate the underlying molecular mechanisms, Intestinal Porcine Epithelial Cell line\u2010J2 (IPEC\u2010J2) cells are treated with L\u2010cit or AMP\u2010activated Protein Kinase (AMPK) inhibitor. AMPK signaling has been activated by L\u2010cit. Notably, Compound C abolishes L\u2010cit's protection on intestinal barrier, mitochondrial function, and antioxidative capacity in IPEC\u2010J2 cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>L\u2010cit may restrain ferritinophagy and ferroptosis to regulate iron metabolism, and induce AMPK pathway activation, which contributes to exert antioxidation, ameliorate iron metabolism and mitochondrial quality control, and improve intestinal microbiota. L\u2010cit is a promising therapeutic strategy for iron overload\u2010induced intestinal injury.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mnfr.202300723","type":"journal-article","created":{"date-parts":[[2024,3,1]],"date-time":"2024-03-01T08:10:53Z","timestamp":1709280653000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["L\u2010Citrulline Ameliorates Iron Metabolism and Mitochondrial Quality Control via Activating AMPK Pathway in Intestine and Improves Microbiota in Mice with Iron Overload"],"prefix":"10.1002","volume":"68","author":[{"given":"Dai","family":"Zhao","sequence":"first","affiliation":[{"name":"College of Veterinary Medicine Huazhong Agricultural University  No.1 Shizishan Street, Hongshan District Wuhan Hubei 430070 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Gao","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine Huazhong Agricultural University  No.1 Shizishan Street, Hongshan District Wuhan Hubei 430070 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiqin","family":"Chen","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine Huazhong Agricultural University  No.1 Shizishan Street, Hongshan District Wuhan Hubei 430070 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingsi","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine Huazhong Agricultural University  No.1 Shizishan Street, Hongshan District Wuhan Hubei 430070 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yian","family":"Deng","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine Huazhong Agricultural University  No.1 Shizishan Street, Hongshan District Wuhan Hubei 430070 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sai","family":"Niu","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine Huazhong Agricultural University  No.1 Shizishan Street, Hongshan District Wuhan Hubei 430070 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6753-9703","authenticated-orcid":false,"given":"Hanchuan","family":"Dai","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine Huazhong Agricultural University  No.1 Shizishan Street, Hongshan District Wuhan Hubei 430070 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,3]]},"reference":[{"key":"e_1_2_10_1_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.59092"},{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13238-014-0083-7"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/hdi.12542"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-020-00253-0"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2019002907"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-030-62026-4_4"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2016.1187366"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2020.08.009"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2021.1911016"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2018.07.020"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2014-307720"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2018.12.012"},{"key":"e_1_2_10_13_1","first-page":"1","volume":"2019","author":"He H.","year":"2019","journal-title":"Oxid. 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