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Our study reveals that the tumour-secreted interleukin-like cytokine Upd3 induces fat-body expression of\n                    <jats:italic>Pepck1<\/jats:italic>\n                    and\n                    <jats:italic>Pdk<\/jats:italic>\n                    , key regulators of gluconeogenesis, disrupting glucose metabolism and contributing to cachexia. Similarly, in mouse cancer cachexia models, we observe IL-6\u2013JAK\u2013STAT-signalling-mediated induction of\n                    <jats:italic>Pck1<\/jats:italic>\n                    and\n                    <jats:italic>Pdk3<\/jats:italic>\n                    expression in the liver. Increased expression of these genes in fly, mouse, and human correlates with poor prognosis, and hepatic expression of\n                    <jats:italic>Pdk3<\/jats:italic>\n                    emerges as a previously unknown mechanism contributing to metabolic dysfunction in cancer cachexia. This study highlights the conserved nature of tumour-induced metabolic disruptions and identifies potential therapeutic targets to mitigate cachexia in people with cancer.\n                  <\/jats:p>","DOI":"10.1038\/s42255-025-01265-2","type":"journal-article","created":{"date-parts":[[2025,4,16]],"date-time":"2025-04-16T05:02:49Z","timestamp":1744779769000},"page":"823-841","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["Hepatic gluconeogenesis and PDK3 upregulation drive cancer cachexia in flies and mice"],"prefix":"10.1038","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6419-1980","authenticated-orcid":false,"given":"Ying","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ezequiel","family":"Dantas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam","family":"Ferrer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Miao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mujeeb","family":"Qadiri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yifang","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4125-0703","authenticated-orcid":false,"given":"Aram","family":"Comjean","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma E.","family":"Davidson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7688-076X","authenticated-orcid":false,"given":"Tiffany","family":"Perrier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanvir","family":"Ahmed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1494-1402","authenticated-orcid":false,"given":"Yanhui","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcus D.","family":"Goncalves","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7820-3727","authenticated-orcid":false,"given":"Tobias","family":"Janowitz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7542-472X","authenticated-orcid":false,"given":"Norbert","family":"Perrimon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,4,16]]},"reference":[{"key":"1265_CR1","doi-asserted-by":"publisher","first-page":"1824","DOI":"10.1016\/j.cell.2023.03.028","volume":"186","author":"M Ferrer","year":"2023","unstructured":"Ferrer, M. et al. 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