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Detection of the early signs of the disease may contribute to the effective attenuation of associated symptoms. Despite playing a central role in the control of metabolism and inflammation, the liver has received little attention in cachexia. We previously described relevant disruption of metabolic pathways in the organ in an animal model of cachexia, and herein, we adopt the same model to investigate temporal onset of inflammation in the liver. The aim was thus to study inflammation in rodent liver in the well\u2010characterized cachexia model of Walker 256 carcinosarcoma and, in addition, to describe inflammatory alterations in the liver of one cachectic colon cancer patient, as compared to one control and one weight\u2010stable cancer patient.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Colon cancer patients (one weight stable [WSC] and one cachectic [CC]) and one patient undergoing surgery for cholelithiasis (control, <jats:italic>n<\/jats:italic>\u00a0=\u00a01) were enrolled in the study, after obtainment of fully informed consent. Eight\u2010week\u2010old male rats were subcutaneously inoculated with a Walker 256 carcinosarcoma cell suspension (2\u00a0\u00d7\u00a010<jats:sup>7<\/jats:sup> cells in 1.0\u00a0mL; tumour\u2010bearing [T]; or phosphate\u2010buffered saline\u2014controls [C]). The liver was excised on Days 0 (<jats:italic>n<\/jats:italic>\u00a0=\u00a05), 7 (<jats:italic>n<\/jats:italic>\u00a0=\u00a05) and 14 (<jats:italic>n<\/jats:italic>\u00a0=\u00a05) after tumour cell injection.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In rodent cachexia, we found progressively higher numbers of CD68<jats:sup>+<\/jats:sup> myeloid cells in the liver along cancer\u2010cachexia development. Similar findings are described for CC, whose liver showed infiltration of the same cell type, compared with both WSC and control patient organs. In advanced rodent cachexia, hepatic phosphorylated c\u2010Jun N\u2010terminal kinase protein content and the inflammasome pathway protein expression were increased in relation to baseline (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05). These changes were accompanied by augmented expression of the active interleukin\u20101\u03b2 (IL\u20101\u03b2) form (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05 for both circulating and hepatic content).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The results show that cancer cachexia is associated with an increase in the number of myeloid cells in rodent and human liver and with modulation of hepatic inflammasome pathway. The latter contributes to the aggravation of systemic inflammation, through increased release of IL\u20101\u03b2.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcsm.13236","type":"journal-article","created":{"date-parts":[[2023,5,13]],"date-time":"2023-05-13T06:40:02Z","timestamp":1683960002000},"page":"1621-1630","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Cachexia causes time\u2010dependent activation of the inflammasome in the liver"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6669-6002","authenticated-orcid":false,"given":"Rodrigo Xavier","family":"das Neves","sequence":"first","affiliation":[{"name":"Cancer Metabolism Research Group, Department of Surgery and LIM26\u2010HCFMUSP Faculdade de Medicina University of S\u00e3o Paulo  S\u00e3o Paulo Brazil"},{"name":"LICI, Center for Cancer Research National Cancer Institute  Bethesda MD USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alex S.","family":"Yamashita","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics, Institute of Biomedical Sciences University of S\u00e3o Paulo  S\u00e3o Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniela M.R.","family":"Riccardi","sequence":"additional","affiliation":[{"name":"Cancer Metabolism Research Group, Department of Surgery and LIM26\u2010HCFMUSP Faculdade de Medicina University of S\u00e3o Paulo  S\u00e3o Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julia","family":"K\u00f6hn\u2010Gaone","sequence":"additional","affiliation":[{"name":"Department of Surgery School of Veterinary Medicine and Animal Science of University of S\u00e3o Paulo\u2014FMVZ\/USP  S\u00e3o Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rodolfo G.","family":"Camargo","sequence":"additional","affiliation":[{"name":"Cancer Metabolism Research Group, Department of Surgery and LIM26\u2010HCFMUSP Faculdade de Medicina University of S\u00e3o Paulo  S\u00e3o Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nelson I.","family":"Neto","sequence":"additional","affiliation":[{"name":"Department of Physiology Federal University of S\u00e3o Paulo  S\u00e3o Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniela","family":"Caetano","sequence":"additional","affiliation":[{"name":"Cancer Metabolism Research Group, Department of Surgery and LIM26\u2010HCFMUSP Faculdade de Medicina University of S\u00e3o Paulo  S\u00e3o Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silvio P.","family":"Gomes","sequence":"additional","affiliation":[{"name":"Cancer Metabolism Research Group, Department of Surgery and LIM26\u2010HCFMUSP Faculdade de Medicina University of S\u00e3o Paulo  S\u00e3o Paulo Brazil"},{"name":"Department of Surgery School of Veterinary Medicine and Animal Science of University of S\u00e3o Paulo\u2014FMVZ\/USP  S\u00e3o Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Felipe H.","family":"Santos","sequence":"additional","affiliation":[{"name":"Laboratory of Adipose Tissue Biology, Center for Integrated Biotechnology University of Mogi das Cruzes  S\u00e3o Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joanna D.C.C.","family":"Lima","sequence":"additional","affiliation":[{"name":"Cancer Metabolism Research Group, Department of Surgery and LIM26\u2010HCFMUSP Faculdade de Medicina University of S\u00e3o Paulo  S\u00e3o Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"suffix":"Jr","given":"Miguel L.","family":"Batista","sequence":"additional","affiliation":[{"name":"Laboratory of Adipose Tissue Biology, Center for Integrated Biotechnology University of Mogi das Cruzes  S\u00e3o Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9 Cesar","family":"Rosa\u2010Neto","sequence":"additional","affiliation":[{"name":"Immunometabolism Research Group, Department of Cell and Developmental Biology, Institute of Biomedical Sciences University of S\u00e3o Paulo  S\u00e3o Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paulo S\u00e9rgio","family":"Martins De Alc\u00e2ntara","sequence":"additional","affiliation":[{"name":"Cancer Metabolism Research Group, Department of Surgery and LIM26\u2010HCFMUSP Faculdade de Medicina University of S\u00e3o Paulo  S\u00e3o Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linda F.","family":"Maximiano","sequence":"additional","affiliation":[{"name":"Cancer Metabolism Research Group, Department of Surgery and LIM26\u2010HCFMUSP Faculdade de Medicina University of S\u00e3o Paulo  S\u00e3o Paulo 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