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The colon adenocarcinoma C26c20 cell line secretes the cytokine leukaemia inhibitory factor (LIF), which induces cachexia. We characterized how LIF promotes cachexia\u2010associated weight loss and anorexia in mice through Janus kinase (JAK)\u2010dependent changes in adipose and hypothalamic tissues.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Cachexia was induced\n                      <jats:italic>in vivo<\/jats:italic>\n                      with the heterotopic allotransplanted administration of C26c20 colon adenocarcinoma cells or the intraperitoneal administration of recombinant LIF in the absence or presence of JAK inhibitors. Blood, adipose, and hypothalamic tissues were collected and processed for cytokine\/adipokine enzyme\u2010linked immunosorbent assays, immunoblot analysis, and quantitative reverse transcription polymerase chain reaction (RT\u2010PCR). Cachexia\u2010associated lipolysis was induced\n                      <jats:italic>in vitro<\/jats:italic>\n                      by stimulating differentiated adipocytes with recombinant LIF or interleukin (IL)\u20106 in the absence or presence of lipase or JAK inhibitors. These adipocytes were processed for glycerol release into the media, immunoblot analysis, and RT\u2010PCR.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Tumour\u2010secreted LIF induced changes in adipose tissue expression and serum levels of IL\u20106 and leptin in a JAK\u2010dependent manner influencing cachexia\u2010associated adipose wasting and anorexia. We identified two JAK inhibitors that block IL\u20106 family\u2010mediated adipocyte lipolysis and IL\u20106 induction using an\n                      <jats:italic>in vitro<\/jats:italic>\n                      cachexia lipolysis assay. JAK inhibitors administered to the\n                      <jats:italic>in vivo<\/jats:italic>\n                      C26c20 cancer cachexia mouse models led to (i) a decrease in signal transducer and activator of transcription 3 phosphorylation in hypothalamic and adipose tissues, (ii) a reverse in the cachexia serum cytokine\/adipokine signature, (iii) a delay in cancer cachexia\u2010associated anorexia and adipose loss, and (iv) an improvement in overall survival.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      JAK inhibitors suppress LIF\u2010associated adipose loss and anorexia in both\n                      <jats:italic>in vitro<\/jats:italic>\n                      and\n                      <jats:italic>in vivo<\/jats:italic>\n                      models of cancer cachexia.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/rco2.24","type":"journal-article","created":{"date-parts":[[2020,7,22]],"date-time":"2020-07-22T02:07:06Z","timestamp":1595383626000},"page":"115-128","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["Janus kinase inhibitors suppress cancer cachexia\u2010associated anorexia and adipose wasting in mice"],"prefix":"10.1002","volume":"3","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0366-311X","authenticated-orcid":false,"given":"Gurpreet K.","family":"Arora","sequence":"first","affiliation":[{"name":"Department of Molecular Genetics University of Texas (UT) Southwestern Medical Center  Dallas TX USA"},{"name":"Department of Radiation Oncology University of Texas (UT) Southwestern Medical Center  Dallas TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arun","family":"Gupta","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology University of Texas (UT) Southwestern Medical Center  Dallas TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6415-3378","authenticated-orcid":false,"given":"Tong","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics University of Texas (UT) Southwestern Medical Center  Dallas TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7704-2546","authenticated-orcid":false,"given":"Aakash Y.","family":"Gandhi","sequence":"additional","affiliation":[{"name":"Center for Human Nutrition University of Texas (UT) Southwestern Medical Center  Dallas TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron","family":"Laine","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology University of Texas (UT) Southwestern Medical Center  Dallas TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorothy L.","family":"Williams","sequence":"additional","affiliation":[{"name":"Center for Human Nutrition University of Texas (UT) Southwestern Medical Center  Dallas TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chul","family":"Ahn","sequence":"additional","affiliation":[{"name":"Harold C. 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