{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T22:53:22Z","timestamp":1772664802985,"version":"3.50.1"},"reference-count":52,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2019,9,10]],"date-time":"2019-09-10T00:00:00Z","timestamp":1568073600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["5R01DK081842, DAM; 5UL1 TR001420, DAM"],"award-info":[{"award-number":["5R01DK081842, DAM; 5UL1 TR001420, DAM"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Research Service of the Department of Veterans Affairs","award":["2I01 BX001140, DAM"],"award-info":[{"award-number":["2I01 BX001140, DAM"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>High tissue iron levels are a risk factor for multiple chronic diseases including type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD). To investigate causal relationships and underlying mechanisms, we used an established NAFLD model\u2014mice fed a high fat diet with supplemental fructose in the water (\u201cfast food\u201d, FF). Iron did not affect excess hepatic triglyceride accumulation in the mice on FF, and FF did not affect iron accumulation compared to normal chow. Mice on low iron are protected from worsening of markers for non-alcoholic steatohepatitis (NASH), including serum transaminases and fibrotic gene transcript levels. These occurred prior to the onset of significant insulin resistance or changes in adipokines. Transcriptome sequencing revealed the major effects of iron to be on signaling by the transforming growth factor beta (TGF-\u03b2) pathway, a known mechanistic factor in NASH. High iron increased fibrotic gene expression in vitro, demonstrating that the effect of dietary iron on NASH is direct. Conclusion: A lower tissue iron level prevents accelerated progression of NAFLD to NASH, suggesting a possible therapeutic strategy in humans with the disease.<\/jats:p>","DOI":"10.3390\/nu11092172","type":"journal-article","created":{"date-parts":[[2019,9,10]],"date-time":"2019-09-10T10:52:26Z","timestamp":1568112746000},"page":"2172","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["A Low Iron Diet Protects from Steatohepatitis in a Mouse Model"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5256-6565","authenticated-orcid":false,"given":"Lipika","family":"Salaye","sequence":"first","affiliation":[{"name":"Center on Diabetes, Obesity and Metabolism, Department of Internal Medicine, Wake Forest Baptist Medical Center, Winston-Salem, NC 27101, 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27157, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6620-8961","authenticated-orcid":false,"given":"Soh-hyun","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Utah Medical Center, Salt Lake City, UT 84112, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert","family":"Cooksey","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Utah Medical Center, Salt Lake City, UT 84112, USA"},{"name":"VA Medical Center, Salt Lake City, UT 84148, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3686-5327","authenticated-orcid":false,"given":"George L.","family":"Donati","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Wake Forest University, Winston-Salem, NC 27109, 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