{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T15:52:14Z","timestamp":1773676334583,"version":"3.50.1"},"reference-count":45,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2018,7,2]],"date-time":"2018-07-02T00:00:00Z","timestamp":1530489600000},"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":["81570756"],"award-info":[{"award-number":["81570756"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003399","name":"Shanghai Municipal Science and Technology Commission","doi-asserted-by":"publisher","award":["15XD1500500"],"award-info":[{"award-number":["15XD1500500"]}],"id":[{"id":"10.13039\/501100003399","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Obesity"],"published-print":{"date-parts":[[2018,8]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Identification of novel regulators involved in adipose development is important to understand the molecular mechanism underlying obesity and associated metabolic disorders. Through isolation and analysis of a vitamin K epoxide reductase <jats:italic>Vkorc1l1<\/jats:italic> mutant, this study aimed to disclose its function and underlying mechanism in adipose development and to obtain valuable insights regarding the mechanism of obesity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A <jats:italic>Vkorc1l1<\/jats:italic> mutation recovered from a forward genetic screen for obesity\u2010related loci in mice was characterized to explore its effects in gene expression, animal metabolism, and adipose development. Adipogenesis was evaluated in both <jats:italic>Vkorc1l1<\/jats:italic> mutant stromal vascular fraction and <jats:italic>Vkorc1l1<\/jats:italic> knockdown preadipocytes. Intracellular vitamin K<jats:sub>2<\/jats:sub> level and the effect of vitamin K<jats:sub>2<\/jats:sub> on adipogenesis were tested in primary preadipocytes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p><jats:italic>Vkorc1l1<\/jats:italic> mutants displayed a considerably lower fat to body weight ratio, substantially decreased plasma leptin, and significantly underdeveloped white adipose tissue. Adipogenic defects related with <jats:italic>Vkorc1l1<\/jats:italic> deficiency were observed both <jats:italic>in vivo<\/jats:italic> and <jats:italic>in vitro<\/jats:italic>. Vitamin K<jats:sub>2<\/jats:sub> could inhibit adipogenesis in stromal vascular fraction. Increased intracellular vitamin K<jats:sub>2<\/jats:sub> level was detected in <jats:italic>Vkorc1l1<\/jats:italic> mutant preadipocytes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p><jats:italic>Vkorc1l1<\/jats:italic> promotes adipogenesis and possibly obesity. Downregulation of <jats:italic>Vkorc1l1<\/jats:italic> increases intracellular vitamin K<jats:sub>2<\/jats:sub> level and impedes preadipocyte differentiation.<\/jats:p><\/jats:sec>","DOI":"10.1002\/oby.22206","type":"journal-article","created":{"date-parts":[[2018,7,2]],"date-time":"2018-07-02T10:33:28Z","timestamp":1530527608000},"page":"1303-1311","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["The Vitamin K Epoxide Reductase <i>Vkorc1l1<\/i> Promotes Preadipocyte Differentiation in Mice"],"prefix":"10.1002","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6561-4810","authenticated-orcid":false,"given":"Yi","family":"Ding","sequence":"first","affiliation":[{"name":"State Key Laboratory of Genetic Engineering and National Center for International Research of Development and Disease, Institute of Developmental Biology and Molecular Medicine, Collaborative Innovation Center of Genetics and 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