{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,30]],"date-time":"2026-05-30T01:39:09Z","timestamp":1780105149422,"version":"3.54.0"},"reference-count":44,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2020,4,24]],"date-time":"2020-04-24T00:00:00Z","timestamp":1587686400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Basic Research Program of China","doi-asserted-by":"publisher","award":["2018YFA0507802"],"award-info":[{"award-number":["2018YFA0507802"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Basic Research Program of China","doi-asserted-by":"publisher","award":["2018YFA0507801"],"award-info":[{"award-number":["2018YFA0507801"]}],"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","award":["81900797"],"award-info":[{"award-number":["81900797"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31530034"],"award-info":[{"award-number":["31530034"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31930057"],"award-info":[{"award-number":["31930057"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31570791"],"award-info":[{"award-number":["31570791"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2018M640565"],"award-info":[{"award-number":["2018M640565"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2020,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Iron homeostasis is essential for maintaining cellular function in a wide range of cell types. However, whether iron affects the thermogenic properties of adipocytes is currently unknown. Using integrative analyses of multi\u2010omics data, transferrin receptor 1 (Tfr1) is identified as a candidate for regulating thermogenesis in beige adipocytes. Furthermore, it is shown that mice lacking <jats:italic>Tfr1<\/jats:italic> specifically in adipocytes have impaired thermogenesis, increased insulin resistance, and low\u2010grade inflammation accompanied by iron deficiency and mitochondrial dysfunction. Mechanistically, the cold treatment in beige adipocytes selectively stabilizes hypoxia\u2010inducible factor 1\u2010alpha (HIF1\u03b1), upregulating the <jats:italic>Tfr1<\/jats:italic> gene, and thermogenic adipocyte\u2010specific <jats:italic>Hif1\u03b1<\/jats:italic> deletion reduces thermogenic gene expression in beige fat without altering core body temperature. Notably, <jats:italic>Tfr1<\/jats:italic> deficiency in interscapular brown adipose tissue (iBAT) leads to the transdifferentiation of brown preadipocytes into white adipocytes and muscle cells; in contrast, long\u2010term exposure to a low\u2010iron diet fails to phenocopy the transdifferentiation effect found in <jats:italic>Tfr1<\/jats:italic>\u2010deficient mice. Moreover, mice lacking transmembrane serine protease 6 (Tmprss6) develop iron deficiency in both inguinal white adipose tissue (iWAT) and iBAT, and have impaired cold\u2010induced beige adipocyte formation and brown fat thermogenesis. Taken together, these findings indicate that Tfr1 plays an essential role in thermogenic adipocytes via both iron\u2010dependent and iron\u2010independent mechanisms.<\/jats:p>","DOI":"10.1002\/advs.201903366","type":"journal-article","created":{"date-parts":[[2020,4,24]],"date-time":"2020-04-24T04:11:47Z","timestamp":1587701507000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":59,"title":["Transferrin Receptor 1 Regulates Thermogenic Capacity and Cell Fate in Brown\/Beige Adipocytes"],"prefix":"10.1002","volume":"7","author":[{"given":"Jin","family":"Li","sequence":"first","affiliation":[{"name":"The First Affiliated Hospital Institute of Translational Medicine School of Public Health Zhejiang University School of Medicine  Hangzhou 310058 China"},{"name":"Beijing Advanced Innovation Center for Food Nutrition and Human Health China Agricultural University  Beijing 100193 China"},{"name":"Department of Nutrition Precision Nutrition Innovation Center School of Public Health Zhengzhou University  Zhengzhou 450001 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohan","family":"Pan","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Applied Microbiology Southern China Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application Guangdong Open Laboratory of Applied Microbiology Guangdong Institute of Microbiology Guangdong Academy of Sciences Zhujiang Hospital Southern Medical University  Guangzhou 510070 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guihua","family":"Pan","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Applied Microbiology Southern China Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application Guangdong Open Laboratory of Applied Microbiology Guangdong Institute of Microbiology Guangdong Academy of Sciences Zhujiang Hospital Southern Medical University  Guangzhou 510070 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zijun","family":"Song","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital Institute of Translational Medicine School of Public Health Zhejiang University School of Medicine  Hangzhou 310058 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao","family":"He","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital Institute of Translational Medicine School of Public Health Zhejiang University School of Medicine  Hangzhou 310058 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susu","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Applied Microbiology Southern China Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application Guangdong Open Laboratory of Applied Microbiology Guangdong Institute of Microbiology Guangdong Academy of Sciences Zhujiang Hospital Southern Medical University  Guangzhou 510070 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueru","family":"Ye","sequence":"additional","affiliation":[{"name":"Nanfang Hospital Southern Medical University  Guangzhou 510515 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang","family":"Yang","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital Institute of Translational Medicine School of Public Health Zhejiang University School of Medicine  Hangzhou 310058 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enjun","family":"Xie","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital Institute of Translational Medicine School of Public Health Zhejiang University School of Medicine  Hangzhou 310058 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinhui","family":"Wang","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital Institute of Translational Medicine School of Public Health Zhejiang University School of Medicine  Hangzhou 310058 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xudong","family":"Mai","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Applied Microbiology Southern China Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application Guangdong Open Laboratory of Applied Microbiology Guangdong Institute of Microbiology Guangdong Academy of Sciences Zhujiang Hospital Southern Medical University  Guangzhou 510070 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangju","family":"Yin","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital Institute of Translational Medicine School of Public Health Zhejiang University School of Medicine  Hangzhou 310058 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Biyao","family":"Tang","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital Institute of Translational Medicine School of Public Health Zhejiang University School of Medicine  Hangzhou 310058 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuan","family":"Shu","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital Institute of Translational Medicine School of Public Health Zhejiang University School of Medicine  Hangzhou 310058 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pengyu","family":"Chen","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital Institute of Translational Medicine School of Public Health Zhejiang University School of Medicine  Hangzhou 310058 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoshuang","family":"Dai","sequence":"additional","affiliation":[{"name":"BGI Institute of Applied Agriculture BGI\u2010Shenzhen  Shenzhen 518120 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ye","family":"Tian","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Applied Microbiology Southern China Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application Guangdong Open Laboratory of Applied Microbiology Guangdong Institute of Microbiology Guangdong Academy of Sciences Zhujiang Hospital Southern Medical University  Guangzhou 510070 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liheng","family":"Yao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Applied Microbiology Southern China Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application Guangdong Open Laboratory of Applied Microbiology Guangdong Institute of Microbiology Guangdong Academy of Sciences Zhujiang Hospital Southern Medical University  Guangzhou 510070 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mulan","family":"Han","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Applied Microbiology Southern China Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application Guangdong Open Laboratory of Applied Microbiology Guangdong Institute of Microbiology Guangdong Academy of Sciences Zhujiang Hospital Southern Medical University  Guangzhou 510070 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guohuan","family":"Xu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Applied Microbiology Southern China Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application Guangdong Open Laboratory of Applied Microbiology Guangdong Institute of Microbiology Guangdong Academy of Sciences Zhujiang Hospital Southern Medical University  Guangzhou 510070 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huijie","family":"Zhang","sequence":"additional","affiliation":[{"name":"Nanfang Hospital Southern Medical University  Guangzhou 510515 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Sun","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Applied Microbiology Southern China Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application Guangdong Open Laboratory of Applied Microbiology Guangdong Institute of Microbiology Guangdong Academy of Sciences Zhujiang Hospital Southern Medical University  Guangzhou 510070 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Applied Microbiology Southern China Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application Guangdong Open Laboratory of Applied Microbiology Guangdong Institute of Microbiology Guangdong Academy of Sciences Zhujiang Hospital Southern Medical University  Guangzhou 510070 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8730-0003","authenticated-orcid":false,"given":"Fudi","family":"Wang","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital Institute of Translational Medicine School of Public Health Zhejiang University School of Medicine  Hangzhou 310058 China"},{"name":"Beijing Advanced Innovation Center for Food Nutrition and Human Health China Agricultural University  Beijing 100193 China"},{"name":"Department of Nutrition Precision Nutrition Innovation Center School of Public Health Zhengzhou University  Zhengzhou 450001 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junxia","family":"Min","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital Institute of Translational Medicine School of Public Health Zhejiang University School of Medicine  Hangzhou 310058 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liwei","family":"Xie","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Applied Microbiology Southern China Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application Guangdong Open Laboratory of Applied Microbiology Guangdong Institute of Microbiology Guangdong Academy of Sciences Zhujiang Hospital Southern Medical University  Guangzhou 510070 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,4,24]]},"reference":[{"key":"e_1_2_8_1_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.05.016"},{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature07182"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature12652"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2014.12.005"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3615"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(62)90110-1"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2013.11.017"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/obr.12323"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-014-3298-5"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.53.10.2535"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1530\/EC-18-0054"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-03853-1"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2017.05.073"},{"key":"e_1_2_8_14_1","first-page":"R297","volume":"237","author":"Dillmann E.","year":"1979","journal-title":"Am. J. Physiol."},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/52.5.813"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2018-05-850404"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/7727"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0810780"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2008.11.009"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M803508200"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1511701112"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-04-149773"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.3945\/ajcn.117.155804"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1820051116"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmet.2019.03.008"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI29881"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.139.12.4832"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.7678183"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.2337\/db13-0213"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep27969"},{"key":"e_1_2_8_31_1","first-page":"39","volume":"6","author":"Lin Q.","year":"2015","journal-title":"Front. Endocrinol."},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2018.10.185"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3010228"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.0000258979.92828.bc"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm.2016.96"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2013.01.004"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2014.03.007"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2007.11.016"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1223-17.2017"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13238-018-0580-1"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.25746"},{"key":"e_1_2_8_42_1","first-page":"e4060","volume":"69","author":"Wang X.","year":"2012","journal-title":"J. Vis. Exp."},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp120"},{"key":"e_1_2_8_44_1","first-page":"e50191","volume":"73","author":"Aune U. L.","year":"2013","journal-title":"J. Vis. Exp."}],"container-title":["Advanced Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fadvs.201903366","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.201903366","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/advs.201903366","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.201903366","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T14:00:59Z","timestamp":1759759259000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/advs.201903366"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,4,24]]},"references-count":44,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2020,6]]}},"alternative-id":["10.1002\/advs.201903366"],"URL":"https:\/\/doi.org\/10.1002\/advs.201903366","archive":["Portico"],"relation":{},"ISSN":["2198-3844","2198-3844"],"issn-type":[{"value":"2198-3844","type":"print"},{"value":"2198-3844","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,4,24]]},"assertion":[{"value":"2019-11-28","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-04-24","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"1903366"}}