{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T02:50:35Z","timestamp":1771469435145,"version":"3.50.1"},"reference-count":57,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2023,11,13]],"date-time":"2023-11-13T00:00:00Z","timestamp":1699833600000},"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":["21876180"],"award-info":[{"award-number":["21876180"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Environmental Toxicology"],"published-print":{"date-parts":[[2024,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Arsenic (As) is a highly toxic metalloid that can be found in insufficiently purified drinking water and exerts adverse effects on the physiology of living organisms that can negatively affect human health after subchronic exposure, causing several diseases, such as liver damage. A high\u2010fat diet, which is increasing in frequency worldwide, can aggravate hepatic pathology. However, the mechanisms behind liver injury caused by the combinatory effects of As exposure and a high\u2010fat diet remain unclear. In this study, we investigated such underlying mechanisms by focusing on three different aspects: As biotransformation, pathological liver damage, and differential expression of signaling pathway components. We employed mice that were fed a regular diet or a high\u2010fat diet and exposed them to a range of arsenite concentrations (As(III), 0.05\u201350\u2009mg\/L) for 12\u2009weeks. Our results showed that a high\u2010fat diet increased the absorption of As into the liver and enhanced liver toxicity, which became progressively more severe as the As concentration increased. Co\u2010exposure to a high\u2010fat diet and As(III) activated PI3K\/AKT and PPAR signaling as well as fatty acid metabolism pathways. In addition, the expression of proteins related to lipid cell function, lipid metabolism, and the regulation of body weight was also affected. Our study provides insights into the mechanisms that contribute to liver injury from subchronic combinatory exposure to As and a high\u2010fat diet and showcases the importance of a healthy lifestyle, which may be of particular benefit to people living in areas with high As(III) concentrations, as a means to reduce or prevent aggravated liver damage.<\/jats:p>","DOI":"10.1002\/tox.24037","type":"journal-article","created":{"date-parts":[[2023,11,13]],"date-time":"2023-11-13T07:15:46Z","timestamp":1699859746000},"page":"1323-1334","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Mechanisms underlying the combination effect of arsenite and high\u2010fat diet on aggravating liver injury in mice"],"prefix":"10.1002","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-7671-0777","authenticated-orcid":false,"given":"Zijun","family":"Ye","sequence":"first","affiliation":[{"name":"School of Environmental 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