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However, AMPK also has anti\u2010inflammatory effects, suggesting that in cachexia, a syndrome of inflammatory\u2010driven muscle wasting, AMPK activation could be beneficial. Here we show\u00a0that the AMPK agonist AICAR suppresses IFN\u03b3\/TNF\u03b1\u2010induced atrophy, while the mitochondrial inhibitor metformin does not. IFN\u03b3\/TNF\u03b1 impair mitochondrial oxidative respiration in myotubes and promote a metabolic shift to aerobic glycolysis, similarly to metformin. In contrast, AICAR partially restored metabolic function. The effects of AICAR were prevented by the AMPK inhibitor Compound C and were reproduced with A\u2010769662, a specific AMPK activator. AICAR and A\u2010769662 co\u2010treatment was found to be synergistic, suggesting that the anti\u2010cachectic effects of these drugs are mediated through AMPK activation. AICAR spared muscle mass in mouse models of cancer and LPS induced atrophy. Together, our findings suggest a dual function for AMPK during inflammation\u2010driven atrophy, wherein it can play a protective role when activated exogenously early in disease progression, but may contribute to anabolic suppression and atrophy when activated later through mitochondrial dysfunction and subsequent metabolic stress.<\/jats:p>","DOI":"10.15252\/emmm.201708307","type":"journal-article","created":{"date-parts":[[2018,5,29]],"date-time":"2018-05-29T08:45:32Z","timestamp":1527583532000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":85,"title":["The AMPK agonist 5\u2010aminoimidazole\u20104\u2010carboxamide ribonucleotide (AICAR), but not metformin, prevents inflammation\u2010associated cachectic muscle wasting"],"prefix":"10.1038","volume":"10","author":[{"given":"Derek T","family":"Hall","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takla","family":"Griss","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer F","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brenda Janice","family":"Sanchez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason","family":"Sadek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne Marie K","family":"Tremblay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Souad","family":"Mubaid","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amr","family":"Omer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca J","family":"Ford","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Bedard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnim","family":"Pause","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon S","family":"Wing","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio","family":"Di Marco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory R","family":"Steinberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Russell G","family":"Jones","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4758-4835","authenticated-orcid":false,"given":"Imed\u2010Eddine","family":"Gallouzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2018,5,29]]},"reference":[{"key":"BFEMMM201708307_CR1","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1172\/JCI200420174","volume":"114","author":"S Acharyya","year":"2004","unstructured":"Acharyya S, Ladner KJ, Nelsen LL, Damrauer J, Reiser PJ, Swoap S, Guttridge DC (2004) Cancer cachexia is regulated by selective targeting of skeletal muscle gene products. 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