{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T07:16:21Z","timestamp":1791443781027,"version":"4.3.3"},"reference-count":40,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,9,10]],"date-time":"2025-09-10T00:00:00Z","timestamp":1757462400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008749","name":"American College of Sports Medicine","doi-asserted-by":"publisher","award":["19\u201000890"],"award-info":[{"award-number":["19\u201000890"]}],"id":[{"id":"10.13039\/100008749","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":[[2025,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Cancer promotes muscle wasting through an imbalance in the tightly regulated protein synthesis and degradation processes. An array of intracellular signalling pathways, including mTORC1 and AMPK, regulate protein synthesis, and these pathways are responsive to the muscle's microenvironment and systemic stimuli. Although feeding and fasting are established systemic regulators of muscle mTORC1 and protein synthesis, the cancer environment's impact on these responses during cachexia development is poorly understood. Although the IL\u20106 cytokine family has been widely investigated as a driver of cachexia with several cancers, how this signalling regulates muscle responses to feeding and fasting requires further study. We investigated if the cancer environment alters the feeding and fasting regulation of skeletal muscle protein synthesis and if the IL\u20106 family of cytokines signalling through muscle glycoprotein 130 could regulate this response.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Male C57BL\/6J mice were subcutaneously injected with 1\u2009\u00d7\u200910\n                      <jats:sup>6<\/jats:sup>\n                      LLC cells or PBS. Mice were euthanized 25\u201330\u2009days post\u2010injection after a 12\u2010h dark cycle fast, followed by access to food pellets for 1\u2009h (fed) or immediately sacrificed. To determine AMPK and gp13's regulation of protein synthesis and anabolic signalling, we injected tamoxifen\u2010inducible skeletal muscle AMPKa\n                      <jats:sup>\n                        <jats:bold>1<\/jats:bold>\n                      <\/jats:sup>\n                      a\n                      <jats:sup>\n                        <jats:bold>2<\/jats:bold>\n                      <\/jats:sup>\n                      or gp130 knockout and floxed control mice with LLC cells or PBS. The gastrocnemius muscle was analysed for protein expression.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Feeding increased p\u2010rpS6 and protein synthesis in PBS (2.2\u2010 and 0.4\u2010fold,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001) and LLC mice (1.7\u2010 and 0.9\u2010fold,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001), but overall, LLC significantly reduced p\u2010rpS6 and protein synthesis. Feeding only increased p\u2010AKT in PBS mice (1.5\u2010fold,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001). In\u00a0vitro LLC\u2010conditioned media did not inhibit the insulin induction of myotube p\u2010AKT (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001) and p\u2010rpS6 (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001). Muscle gp130 loss reduced the fasting p\u2010AMPK induction in LLC mice but did not alter suppression of p\u2010AKT and p\u2010rpS6 and protein synthesis. Muscle AMPK loss increased p\u2010rpS6 (2.1\u2010fold,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001) and protein synthesis (0.7\u2010fold,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001) in PBS mice but did not restore LLC\u2010suppressed protein synthesis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our study provides novel insight into muscle responsiveness to feeding and fasting in a cancer environment. We find the acute anabolic response to feeding is maintained during LLC\u2010induced cachexia, whereas the fasting catabolic response is exacerbated. Muscle\u2010specific gp130 loss prevented disrupted fasting AMPK activation but not protein synthesis. There is a need to understand the aberrant upstream and downstream regulation of muscle AMPK activity that is disrupted with cancer and leads to aberrant protein turnover regulation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jcsm.70064","type":"journal-article","created":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T04:50:34Z","timestamp":1757566234000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["The Effect of Cachexia on the Feeding Regulation of Skeletal Muscle Protein Synthesis in Tumour\u2010Bearing Mice"],"prefix":"10.1002","volume":"16","author":[{"given":"Brittany\u00a0R.","family":"Counts","sequence":"first","affiliation":[{"name":"Integrative Muscle Biology Laboratory, Division of Rehabilitation Sciences, College of Health Professions University of Tennessee Health Science Center  Memphis Tennessee USA"},{"name":"Department of Cell, Development and Cancer Biology, Knight Cancer Institute Oregon Health &amp; Science University  Portland Oregon USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6028-6977","authenticated-orcid":false,"given":"Quan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Integrative Muscle Biology Laboratory, Division of Rehabilitation Sciences, College of Health Professions University of Tennessee Health Science Center  Memphis Tennessee USA"},{"name":"Integrative Muscle Biology Lab, Department of Kinesiology &amp; Sport Management Texas A&amp;M University  College Station Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica\u00a0L.","family":"Halle","sequence":"additional","affiliation":[{"name":"Integrative Muscle Biology Laboratory, Division of Rehabilitation Sciences, College of Health Professions University of Tennessee Health Science Center  Memphis Tennessee USA"},{"name":"Oklahoma Medical Research Foundation  Oklahoma City Oklahoma 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