{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T13:34:01Z","timestamp":1790775241008,"version":"4.1.0"},"reference-count":57,"publisher":"The Company of Biologists","license":[{"start":{"date-parts":[[2021,5,18]],"date-time":"2021-05-18T00:00:00Z","timestamp":1621296000000},"content-version":"am","delay-in-days":868,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001459","name":"Ministry of Education - Singapore","doi-asserted-by":"publisher","award":["R154000A23112"],"award-info":[{"award-number":["R154000A23112"]}],"id":[{"id":"10.13039\/501100001459","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>Cancer cachexia affects up to 80% of the patients with advanced solid cancer and leads to excessive muscle wasting. Here, using an inducible zebrafish HCC model driven by oncogenic krasG12V, we observed a progressive muscle wasting phenotype in adult zebrafish, characterized by significant loss of body weight and muscle fibers. By differential feeding, we observed that overfeeding caused fatty liver, accelerated carcinogenesis and muscle wasting. Interestingly, leptin, an obesity hormone, was upregulated in oncogenic hepatocytes and overfeeding groups. We also found a progressively increased leptin expression during human liver disease progression. By using leptin receptor (lepr) knockout fish, we found that tumor fish in the lepr mutant background had a higher survival rate and significantly lower muscle wasting level after tumor induction than the tumor fish in the wildtype background. Chemical inhibitors targeting leptin signaling also alleviated muscle wasting phenotype, indicating that the leptin signaling may be a new therapeutic target for cancer patients with muscle wasting.<\/jats:p>","DOI":"10.1242\/dmm.038240","type":"journal-article","created":{"date-parts":[[2019,2,4]],"date-time":"2019-02-04T14:19:36Z","timestamp":1549289976000},"source":"Crossref","is-referenced-by-count":21,"title":["Leptin induces muscle wasting in <i>kras<\/i>-driven hepatocellular carcinoma (HCC) model in zebrafish"],"prefix":"10.1242","author":[{"given":"Qiqi","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Biological Sciences, National University of Singapore, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuan","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, National University of Singapore, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai 230002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9660-5260","authenticated-orcid":false,"given":"Zhiyuan","family":"Gong","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, National University of Singapore, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2019,1,1]]},"reference":[{"key":"2021042513044290500_DMM038240C1","doi-asserted-by":"publisher","first-page":"17","DOI":"10.4251\/wjgo.v7.i4.17","article-title":"Cancer cachexia, mechanism and treatment","volume":"7","author":"Aoyagi","year":"2015","journal-title":"World J. 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