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CAC affects up to 80% of cancer patients, yet the mechanisms underlying the disease are not well understood and no approved disease\u2010specific medication exists. As a multiorgan disorder, CAC can only be studied on an organismal level. To cover the diverse aetiologies of CAC, researchers rely on the availability of a multifaceted pool of cancer models with varying degrees of cachexia symptoms. So far, no tumour model syngeneic to C57BL\/6 mice exists that allows direct comparison between cachexigenic\u2010 and non\u2010cachexigenic tumours.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      MCA207 and CHX207 fibrosarcoma cells were intramuscularly implanted into male or female, 10\u201311\u2010week\u2010old C57BL\/6J mice. Tumour tissues were subjected to magnetic resonance imaging, immunohistochemical\u2010, and transcriptomic analysis. Mice were analysed for tumour growth, body weight and \u2010composition, food\u2010 and water intake, locomotor activity, O\n                      <jats:sub>2<\/jats:sub>\n                      consumption, CO\n                      <jats:sub>2<\/jats:sub>\n                      production, circulating blood cells, metabolites, and tumourkines. Mice were sacrificed with same tumour weights in all groups. Adipose tissues were examined using high\u2010resolution respirometry, lipolysis measurements\n                      <jats:italic>in vitro<\/jats:italic>\n                      and\n                      <jats:italic>ex vivo<\/jats:italic>\n                      , and radioactive tracer studies\n                      <jats:italic>in vivo<\/jats:italic>\n                      . Gene expression was determined in adipose\u2010 and muscle tissues by quantitative PCR and Western blotting analyses. Muscles and cultured myotubes were analysed histologically and by immunofluorescence microscopy for myofibre cross sectional area and myofibre diameter, respectively. Interleukin\u20106 (\n                      <jats:italic>Il\u20106<\/jats:italic>\n                      ) was deleted from cancer cells using CRISPR\/Cas9 mediated gene editing.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      CHX207, but not MCA207\u2010tumour\u2010bearing mice exhibited major clinical features of CAC, including systemic inflammation, increased plasma IL\u20106 concentrations (190\u00a0pg\/mL,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0\u2264\u00a00.0001), increased energy expenditure (+28%,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0\u2264\u00a00.01), adipose tissue loss (\u221247%,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0\u2264\u00a00.0001), skeletal muscle wasting (\u221218%,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0\u2264\u00a00.001), and body weight reduction (\u221213%,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0\u2264\u00a00.01) 13\u00a0days after cancer cell inoculation. Adipose tissue loss resulted from reduced lipid uptake and \u2010synthesis combined with increased lipolysis but was not associated with elevated beta\u2010adrenergic signalling or adipose tissue browning. Muscle atrophy was evident by reduced myofibre cross sectional area (\u221221.8%,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0\u2264\u00a00.001), increased catabolic\u2010 and reduced anabolic signalling. Deletion of IL\u20106 from CHX207 cancer cells completely protected CHX207\n                      <jats:sup>IL6KO<\/jats:sup>\n                      \u2010tumour\u2010bearing mice from CAC.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In this study, we present CHX207 fibrosarcoma cells as a novel tool to investigate the mediators and metabolic consequences of CAC in C57BL\/6 mice in comparison to non\u2010cachectic MCA207\u2010tumour\u2010bearing mice. IL\u20106 represents an essential trigger for CAC development in CHX207\u2010tumour\u2010bearing mice.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jcsm.13109","type":"journal-article","created":{"date-parts":[[2022,11,9]],"date-time":"2022-11-09T18:38:29Z","timestamp":1668019109000},"page":"93-107","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":61,"title":["Interleukin\u20106 initiates muscle\u2010 and adipose tissue wasting in a novel C57BL\/6 model of cancer\u2010associated cachexia"],"prefix":"10.1002","volume":"14","author":[{"given":"Isabella","family":"Pototschnig","sequence":"first","affiliation":[{"name":"Institute of Molecular Biosciences University of Graz  Graz Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ursula","family":"Feiler","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biosciences University of Graz  Graz 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