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High PDK4 and abnormal energetic metabolism were found in the skeletal muscle of colon\u201026 tumor hosts, as well as in mice fed a diet enriched in Pirinixic acid, previously shown to increase PDK4 levels. Viral\u2010mediated PDK4 over\u2010expression in myotube cultures was sufficient to promote myofiber shrinkage, consistent with enhanced protein catabolism and mitochondrial abnormalities. On the contrary, blockade of PDK4 was sufficient to restore myotube size in C2C12 cultures exposed to tumor media. Our data support, for the first time, a direct role for PDK4 in promoting cancer\u2010associated muscle metabolic alterations and skeletal muscle atrophy.\u2014Pin, F., Novinger, L. J., Huot, J. R., Harris, R. A., Couch, M. E., O'Connell, T. M., Bonetto, A. PDK4 drives metabolic alterations and muscle atrophy in cancer cachexia. FASEB J. 33, 7778\u20137790 (2019).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.201802799r","type":"journal-article","created":{"date-parts":[[2019,3,20]],"date-time":"2019-03-20T21:53:27Z","timestamp":1553118807000},"page":"7778-7790","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":75,"title":["PDK4 drives metabolic alterations and muscle atrophy in cancer cachexia"],"prefix":"10.1096","volume":"33","author":[{"given":"Fabrizio","family":"Pin","sequence":"first","affiliation":[{"name":"Department of Anatomy and Cell Biology Indiana University School of Medicine Indianapolis Indiana USA"},{"name":"Indiana University-Purdue University Indianapolis Center for Cachexia Research, Innovation, and Therapy Indiana University School of Medicine Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leah J.","family":"Novinger","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology-Head and Neck Surgery Indiana University School of Medicine Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua R.","family":"Huot","sequence":"additional","affiliation":[{"name":"Indiana University-Purdue University Indianapolis Center for Cachexia Research, Innovation, and Therapy Indiana University School of Medicine Indianapolis Indiana USA"},{"name":"Department of Surgery Indiana University School of Medicine Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert A.","family":"Harris","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology Indiana University School of Medicine Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marion E.","family":"Couch","sequence":"additional","affiliation":[{"name":"Indiana University-Purdue University Indianapolis Center for Cachexia Research, Innovation, and Therapy Indiana University School of Medicine Indianapolis Indiana USA"},{"name":"Department of Otolaryngology-Head and Neck Surgery Indiana University School of Medicine Indianapolis Indiana USA"},{"name":"Simon Cancer Center Indiana University School of Medicine Indianapolis Indiana USA"},{"name":"Indiana Center for Musculoskeletal Health Indiana University School of Medicine Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas M.","family":"O'Connell","sequence":"additional","affiliation":[{"name":"Indiana University-Purdue University Indianapolis Center for Cachexia Research, Innovation, and Therapy Indiana University School of Medicine Indianapolis Indiana USA"},{"name":"Department of Otolaryngology-Head and Neck Surgery Indiana University School of Medicine Indianapolis Indiana USA"},{"name":"Simon Cancer Center Indiana University School of Medicine Indianapolis Indiana USA"},{"name":"Indiana Center for Musculoskeletal Health Indiana University School of Medicine Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Bonetto","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Cell Biology Indiana University School of Medicine Indianapolis Indiana USA"},{"name":"Indiana University-Purdue University Indianapolis Center for Cachexia Research, Innovation, and Therapy Indiana University School of Medicine Indianapolis Indiana USA"},{"name":"Department of Otolaryngology-Head and Neck Surgery Indiana University School of Medicine Indianapolis Indiana USA"},{"name":"Department of Surgery Indiana University School of Medicine Indianapolis Indiana USA"},{"name":"Simon Cancer Center Indiana University School of Medicine Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,3,20]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrclinonc.2012.209"},{"key":"e_1_2_9_3_1","first-page":"153","article-title":"Cancer cachexia: mediators, signaling, and metabolic pathways","volume":"16","author":"Fearon K. 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