{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T07:16:20Z","timestamp":1791443780967,"version":"4.3.3"},"reference-count":40,"publisher":"American Physiological Society","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Endocrinology and Metabolism"],"published-print":{"date-parts":[[2013,5,15]]},"abstract":"<jats:p>\n                    Although catabolic signaling has a well-established role in muscle wasting during cancer cachexia, the suppression of anabolic signaling also warrants further investigation. In cachectic tumor-bearing mice, circulating IL-6 levels are associated with suppressed muscle protein synthesis and mTORC1 signaling. We have found AMPK and IGF-I\/insulin signaling, two well-known regulators of the mammalian target of rapamycin (mTOR), are altered with the progression of cachexia. How IL-6 can induce suppression of mTORC1 signaling remains to be established. The purpose of this study was to examine mTOR complex 1 (mTORC1) activation and regulation by IL-6 during cancer cachexia. IL-6 effects on mTOR activation were examined in Apc\n                    <jats:sup>Min\/+<\/jats:sup>\n                    mouse skeletal muscle and C\n                    <jats:sub>2<\/jats:sub>\n                    C\n                    <jats:sub>12<\/jats:sub>\n                    myotubes. Systemic IL-6 overexpression in Apc\n                    <jats:sup>Min\/+<\/jats:sup>\n                    mice produced a dose-dependent suppression of mTOR signaling that corresponded to induction of STAT3 and AMPK phosphorylation. This result was also evident in IL-6-treated myotubes. Basal mTOR activation and mTOR responsiveness to glucose administration were suppressed in cachectic skeletal muscle. However, insulin induction of mTOR activity was maintained in IL-6-treated myotubes. Whereas IL-6 suppression of myotube mTOR activity was rescued by AMPK inhibition, inhibition of STAT3 signaling was not sufficient to rescue IL-6 suppression of mTOR activity. Last, treadmill exercise training was able to prevent IL-6-induced inhibition of mTOR signaling in Apc\n                    <jats:sup>Min\/+<\/jats:sup>\n                    mice independently of activated STAT. In conclusion, we report dose-dependent suppression of mTOR activity by IL-6 and suppressed mTOR responsiveness to glucose administration in Apc\n                    <jats:sup>Min\/+<\/jats:sup>\n                    mice. IL-6 suppression of mTOR activity was dependent on AMPK activation and independent of STAT signaling in myotubes.\n                  <\/jats:p>","DOI":"10.1152\/ajpendo.00410.2012","type":"journal-article","created":{"date-parts":[[2013,3,27]],"date-time":"2013-03-27T00:54:43Z","timestamp":1364345683000},"page":"E1042-E1052","source":"Crossref","is-referenced-by-count":176,"title":["Muscle mTORC1 suppression by IL-6 during cancer cachexia: a role for AMPK"],"prefix":"10.1152","volume":"304","author":[{"given":"James P.","family":"White","sequence":"first","affiliation":[{"name":"Integrative Muscle Biology Laboratory, Exercise Science Department, University of South Carolina, Columbia South Carolina; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa J.","family":"Puppa","sequence":"additional","affiliation":[{"name":"Integrative Muscle Biology Laboratory, Exercise Science Department, University of South Carolina, Columbia South Carolina; 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