{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T22:41:55Z","timestamp":1792708915629,"version":"4.5.0"},"reference-count":61,"publisher":"Wiley","issue":"14","license":[{"start":{"date-parts":[[2023,12,27]],"date-time":"2023-12-27T00:00:00Z","timestamp":1703635200000},"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":["82272925"],"award-info":[{"award-number":["82272925"]}],"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":["82274151"],"award-info":[{"award-number":["82274151"]}],"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":["81872494"],"award-info":[{"award-number":["81872494"]}],"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":["82074063"],"award-info":[{"award-number":["82074063"]}],"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":["81873042"],"award-info":[{"award-number":["81873042"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Nutrition Food Res"],"published-print":{"date-parts":[[2024,7]]},"abstract":"<jats:sec><jats:title>Scope<\/jats:title><jats:p>Branched chain amino acids (BCAAs) are essential amino acids and important nutrient signals for energy and protein supplementation. The study uses muscle\u2010specific <jats:italic>branched\u2010chain \u03b1\u2010keto acid dehydrogenase kinase<\/jats:italic> (<jats:italic>Bckdk<\/jats:italic>) conditional knockout (cKO) mice to reveal the contribution of BCAA metabolic dysfunction to muscle wasting.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method and results<\/jats:title><jats:p>Muscle\u2010specific <jats:italic>Bckdk<\/jats:italic>\u2010cKO mice are generated through crossbreeding of <jats:italic>Bckdk<\/jats:italic><jats:sup>f\/f<\/jats:sup> mice with <jats:italic>Myf5<jats:sup>Cre<\/jats:sup><\/jats:italic> mice. Lewis lung cancer (LLC) tumor transplantation is used to establish the cancer cachexia model. The occurrence of cancer cachexia is accelerated in the muscle\u2010specific <jats:italic>Bckdk<\/jats:italic>\u2010cKO mice after bearing LLC tumor. Wasting skeletal muscle is characterized by increased protein ubiquitination degradation and impaired protein synthesis. The wasting muscle gastrocnemius is mechanized as a distinct BCAA metabolic dysfunction. Based on the atrophy phenotype resulting from BCAA metabolism dysfunction, the optimized BCAA supplementation improves the survival of cancer cachexia in muscle\u2010specific <jats:italic>Bckdk<\/jats:italic>\u2010cKO mice bearing LLC tumors, and improves the occurrence of cancer cachexia. The mechanism of BCAA supplementation on muscle mass preservation is based on the promotion of protein synthesis and the inhibition of protein ubiquitination degradation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Dysfunctional BCAA metabolism contributes to the inhibition of protein synthesis and increases protein degradation in the cancer cachexia model of muscle\u2010specific <jats:italic>Bckdk<\/jats:italic>\u2010cKO mice bearing LLC tumors. The reprogramming of BCAA catabolism exerts therapeutic effects by stimulating protein synthesis and inhibiting protein degradation in skeletal muscle.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mnfr.202300577","type":"journal-article","created":{"date-parts":[[2023,12,27]],"date-time":"2023-12-27T21:06:34Z","timestamp":1703711194000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["<i>Bckdk<\/i>\u2010Mediated Branch Chain Amino Acid Metabolism Reprogramming Contributes to Muscle Atrophy during Cancer Cachexia"],"prefix":"10.1002","volume":"68","author":[{"given":"Li","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Pharmacy Shanghai Sixth People's Hospital Affiliated Shanghai Jiao Tong University School of Medicine  Shanghai 200233 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Shanghai Sixth People's Hospital Affiliated Shanghai Jiao Tong University School of Medicine  Shanghai 200233 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengyi","family":"Chi","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Shanghai Sixth People's Hospital Affiliated Shanghai Jiao Tong University School of Medicine  Shanghai 200233 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaxian","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Shanghai Sixth People's Hospital Affiliated Shanghai Jiao Tong University School of Medicine  Shanghai 200233 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinting","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Shanghai Sixth People's Hospital Affiliated Shanghai Jiao Tong University School of Medicine  Shanghai 200233 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leng","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Shanghai Sixth People's Hospital Affiliated Shanghai Jiao Tong University School of Medicine  Shanghai 200233 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Xin","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Shanghai Sixth People's Hospital Affiliated Shanghai Jiao Tong University School of Medicine  Shanghai 200233 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Run","family":"Gan","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Shanghai Sixth People's Hospital Affiliated Shanghai Jiao Tong University School of Medicine  Shanghai 200233 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yixin","family":"Tu","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Shanghai Sixth People's Hospital Affiliated Shanghai Jiao Tong University School of Medicine  Shanghai 200233 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xipeng","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Shanghai Sixth People's Hospital Affiliated Shanghai Jiao Tong University School of Medicine  Shanghai 200233 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Shanghai Sixth People's Hospital Affiliated Shanghai Jiao Tong University School of Medicine  Shanghai 200233 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Shanghai Sixth People's Hospital Affiliated Shanghai Jiao Tong University School of Medicine  Shanghai 200233 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinlu","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Shanghai Sixth People's Hospital Affiliated Shanghai Jiao Tong University School of Medicine  Shanghai 200233 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianping","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Shanghai Sixth People's Hospital Affiliated Shanghai Jiao Tong University School of Medicine  Shanghai 200233 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yonglong","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Shanghai Sixth People's Hospital Affiliated Shanghai Jiao Tong University School of Medicine  Shanghai 200233 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Shanghai Sixth People's Hospital Affiliated Shanghai Jiao Tong University School of Medicine  Shanghai 200233 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0279-8784","authenticated-orcid":false,"given":"Quanjun","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Shanghai Sixth People's Hospital Affiliated Shanghai Jiao Tong University School of Medicine  Shanghai 200233 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,12,27]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(10)70218-7"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMcibr1106880"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1177\/1758835919880084"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41416-022-01826-2"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.12528"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.20.00611"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.esmoop.2021.100092"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clnu.2021.02.005"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12094-018-02009-3"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13539-014-0138-x"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42255-020-00312-4"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2014.171"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12986-018-0271-1"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13624"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41568-018-0074-8"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.3923\/ijp.2021.113.121"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnut.2021.715795"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/bjs.1800760215"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1177\/1559827619874044"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.12781"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clnu.2015.02.004"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/mnfr.202300076"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.12673"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/mnfr.201700756"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41388-020-01480-z"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/d41573-021-00107-6"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.RA120.013121"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41569-022-00760-3"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu12082267"},{"key":"e_1_2_9_30_1","volume":"08","author":"Shao J.","year":"2022","journal-title":"bioRxiv"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2014.11.005"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.12632"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb2015"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00463.2021"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.13391"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/ptr.7132"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jff.2021.104714"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.12208"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10620-014-3086-6"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1249\/MSS.0000000000000272"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1271\/bbb.64.2594"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1002\/mnfr.202300248"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1002\/mnfr.202101030"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0076752"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00100.2004"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(22)02469-2"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.3168\/jds.2019-17147"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2018.10.013"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1021\/pr400281r"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41388-020-1262-z"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.21037\/tlcr-21-885"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41420-021-00602-0"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1155\/2022\/3691635"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-020-2610-1"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.21037\/atm-21-761"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature22314"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1097\/MEG.0000000000000968"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.14309\/ajg.0000000000001301"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nut.2019.110698"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(19860701)58:1<147::AID-CNCR2820580126>3.0.CO;2-I"},{"key":"e_1_2_9_61_1","first-page":"241","volume":"6","author":"Yamanaka H.","year":"1990","journal-title":"Nutrition (Burbank, Los Angeles County, Calif.)"}],"container-title":["Molecular Nutrition &amp; Food Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mnfr.202300577","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,16]],"date-time":"2024-08-16T05:07:38Z","timestamp":1723784858000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mnfr.202300577"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12,27]]},"references-count":61,"journal-issue":{"issue":"14","published-print":{"date-parts":[[2024,7]]}},"alternative-id":["10.1002\/mnfr.202300577"],"URL":"https:\/\/doi.org\/10.1002\/mnfr.202300577","archive":["Portico"],"relation":{},"ISSN":["1613-4125","1613-4133"],"issn-type":[{"value":"1613-4125","type":"print"},{"value":"1613-4133","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,12,27]]},"assertion":[{"value":"2023-08-12","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-12-27","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"2300577"}}