{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T14:11:49Z","timestamp":1787667109026,"version":"build-2736575974"},"reference-count":49,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2023,12,11]],"date-time":"2023-12-11T00:00:00Z","timestamp":1702252800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2024,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and Aims<\/jats:title><jats:p>Disorders in liver lipid metabolism have been implicated in a range of metabolic conditions, including fatty liver and liver cancer. Altered lipid distribution within the liver, shifting from the pericentral to the periportal zone under pathological circumstances, has been observed; however, the underlying mechanism remains elusive. Iron, an essential metal, exhibits a zonal distribution in the liver similar to that of lipids. Nevertheless, the precise relationship between iron and lipid distribution, especially in the pericentral and periportal zones, remains poorly understood.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We conducted comprehensive in\u00a0vitro and in\u00a0vivo experiments, combining with in\u00a0situ analysis and RNA sequencing, aiming for a detailed exploration of the causal relationship between iron accumulation and lipid metabolism.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Our research suggests that iron overload can disrupt the normal distribution of lipids within the liver, particularly in the periportal zone. Through meticulous gene expression profiling in both the pericentral and periportal zones, we identified pyruvate carboxylase (PC) as a pivotal regulator in iron overload\u2010induced lipid accumulation. Additionally, we revealed that the activation of cyclic adenosine monophosphate response element binding protein (CREB) was indispensable for <jats:italic>Pc<\/jats:italic> gene expression when in response to iron overload.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>In summary, our investigation unveils the crucial involvement of iron overload in fostering hepatic lipid accumulation in the periportal zone, at least partly mediated by the modulation of <jats:italic>Pc<\/jats:italic> expression. These insights offer new perspectives for understanding the pathogenesis of fatty liver diseases and their progression.<\/jats:p><\/jats:sec>","DOI":"10.1111\/liv.15807","type":"journal-article","created":{"date-parts":[[2023,12,12]],"date-time":"2023-12-12T19:42:20Z","timestamp":1702410140000},"page":"589-602","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Zonated iron deposition in the periportal zone of the liver is associated with selectively enhanced lipid synthesis"],"prefix":"10.1111","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1388-7697","authenticated-orcid":false,"given":"Qiuyuan","family":"Yang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Environmental Chemistry and Ecotoxicology Research Center for Eco\u2010Environmental Sciences, Chinese Academy of Sciences  Beijing China"},{"name":"University of Chinese Academy of Sciences  Beijing 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Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5643-0734","authenticated-orcid":false,"given":"Sijin","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Environmental Chemistry and Ecotoxicology Research Center for Eco\u2010Environmental Sciences, Chinese Academy of Sciences  Beijing China"},{"name":"University of Chinese Academy of Sciences  Beijing 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