{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T16:54:10Z","timestamp":1774457650213,"version":"3.50.1"},"reference-count":40,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T00:00:00Z","timestamp":1769558400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T00:00:00Z","timestamp":1769558400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100003621","name":"Ministry of Science, ICT and Future Planning","doi-asserted-by":"publisher","award":["NRF\u20102021R1A2C2010460"],"award-info":[{"award-number":["NRF\u20102021R1A2C2010460"]}],"id":[{"id":"10.13039\/501100003621","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003621","name":"Ministry of Science, ICT and Future Planning","doi-asserted-by":"publisher","award":["NRF\u20102022R1A2C2005930"],"award-info":[{"award-number":["NRF\u20102022R1A2C2005930"]}],"id":[{"id":"10.13039\/501100003621","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003621","name":"Ministry of Science, ICT and Future Planning","doi-asserted-by":"publisher","award":["RS\u20102025\u201002243112"],"award-info":[{"award-number":["RS\u20102025\u201002243112"]}],"id":[{"id":"10.13039\/501100003621","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002597","name":"Kyung Hee University","doi-asserted-by":"publisher","award":["KHU\u201020251294"],"award-info":[{"award-number":["KHU\u201020251294"]}],"id":[{"id":"10.13039\/501100002597","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2026,2]]},"abstract":"ABSTRACT<\/jats:title>\n \n Background<\/jats:title>\n Cancer cachexia is a syndrome characterized by significant weight loss, particularly of adipose tissue, which negatively impacts patient survival. Pharmacological approaches to prevent this abnormal fat reduction remain poorly defined. This study investigated the potential of ellagic acid (EA) to mitigate cancer\u2010induced fat loss.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n In vitro, 3T3\u2010L1 adipocytes were exposed to 50% conditioned medium (CM) from CT26 colon cancer cells to mimic cachectic conditions. The effects of EA on lipid accumulation and adipogenesis\u2010related markers (PPAR\u03b3 and RXR\u03b2) were analysed. The mechanism was validated using molecular docking and siRNA\u2010mediated gene silencing. In\u00a0vivo, a cachexia mouse model was established by subcutaneous injection of CT26 cells into BALB\/c mice. Mice were orally administered EA at dose of 10, 20 and 40\u2009mg\/kg, respectively (\n n<\/jats:italic>\n \u2009=\u20097 per group) for 14\u2009days to evaluate its protective effects.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n In 3T3\u2010L1 cells, the 50% CM\u2010treatment reduced lipid accumulation by 14% (\n p<\/jats:italic>\n \u2009<\u20090.05) and downregulated PPAR\u03b3 (\n p<\/jats:italic>\n \u2009<\u20090.05) and RXR\u03b2 (\n p<\/jats:italic>\n \u2009<\u20090.01) expression. The EA treatment restored diminished\u00a0lipid levels and rescued downregulated the expression of PPAR\u03b3 (\n p<\/jats:italic>\n \u2009<\u20090.05) and RXR\u03b2 (\n p<\/jats:italic>\n \u2009<\u20090.01). This pro\u2010adipogenic effect was abolished by siRNA\u2010mediated inhibition of RXR\u03b2. In the cachexia mouse model, EA treatment significantly improved physical performance and body composition. Specifically, EA\u00a0enhanced grip strength by 1.32\u2010fold (10\u2009mg\/kg,\n p<\/jats:italic>\n \u2009<\u20090.0001) and 1.24\u2010fold (20\u2009mg\/kg,\n p<\/jats:italic>\n \u2009<\u20090.001), increased the inguinal white adipose tissue (iWAT) mass by 59.8% (10\u2009mg\/kg,\n p<\/jats:italic>\n \u2009<\u20090.01), and 56.1% (20\u2009mg\/kg,\n p<\/jats:italic>\n \u2009<\u20090.05), and was accompanied by a significant increase in the tumour\u2010free body weight of 6.4% (10\u2009mg\/kg,\n p<\/jats:italic>\n \u2009<\u20090.05), and 5.6% (20\u2009mg\/kg,\n p<\/jats:italic>\n \u2009<\u20090.01) compared to cachectic mice. EA treatment did not affect tumour growth. It increased\u00a0the adipogenesis\u2010related protein expression of C\/EBP\u03b1 (2.1\u2010fold,\n p<\/jats:italic>\n \u2009<\u20090.05), PPAR\u03b3 (1.5\u2010fold,\n p<\/jats:italic>\n \u2009<\u20090.05) and SREBP1 (1.5\u2010fold,\n p<\/jats:italic>\n \u2009<\u20090.05) in the iWAT. The EA treatment enhanced the nuclear localization index of RXR\u03b2 in the iWAT by 0.51 (10\u2009mg\/kg, 1.9\u2010fold,\n p<\/jats:italic>\n \u2009<\u20090.05) and 0.46 (20\u2009mg\/kg, 1.7\u2010fold,\n p<\/jats:italic>\n \u2009<\u20090.05) compared to cachectic mice.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n EA mitigates cancer cachexia\u2010induced fat loss by the activation of the RXR\u03b2\u2013PPAR\u03b3 pathway. These findings present EA as a potential pharmacological agent to improve the abnormal fat reduction and muscle dysfunction associated with cachexia.<\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/jcsm.70176","type":"journal-article","created":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T10:40:02Z","timestamp":1769596802000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Ellagic Acid Alleviates Abnormal Fat Reduction by Activating the RXR\u03b2\u2013PPAR\u03b3 Pathways in a CT26 Tumour\u2010Induced Cachexia Mouse Model"],"prefix":"10.1002","volume":"17","author":[{"given":"Woo\u00a0Yong","family":"Park","sequence":"first","affiliation":[{"name":"Department of Pharmacology, College of Korean Medicine Kyung Hee University Seoul Republic of Korea"},{"name":"Kyung Hee Institute of Convergence Korean Medicine Kyung Hee University Seoul Republic of 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