{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T14:45:38Z","timestamp":1791989138780,"version":"4.4.0"},"posted":{"date-parts":[[2025,5,20]]},"group-title":"Cancer Biology","reference-count":60,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,5,20]],"date-time":"2025-05-20T00:00:00Z","timestamp":1747699200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"award":["CGCATF-2021\/100034"],"award-info":[{"award-number":["CGCATF-2021\/100034"]}],"id":[{"id":"https:\/\/ror.org\/054225q67","id-type":"ROR","asserted-by":"publisher"}]},{"award":["OT2CA278654"],"award-info":[{"award-number":["OT2CA278654"]}],"id":[{"id":"https:\/\/ror.org\/040gcmg81","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["CA163591"],"award-info":[{"award-number":["CA163591"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,5,20]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Cancer cachexia is an involuntary weight loss condition characterized by systemic metabolic disorder. A comprehensive flux characterization of this condition however is lacking. Here, we systematically isotope traced eight major circulating nutrients in mice bearing cachectic C26 tumors (cxC26) and food intake-matched mice bearing non-cachectic C26 tumors (ncxC26). We found no difference in whole-body lipolysis and proteolysis, ketogenesis, or fatty acid and ketone oxidation by tissues between the two groups. In contrast, compared to ncxC26 mice ad libitum, glucose turnover flux decreased in food intake-controlled ncxC26 mice but not in cxC26 mice. Similarly, sustained glucose turnover flux was observed in two autochthonous cancer cachexia models despite reduced food intake. We identified glutamine and alanine as responsible for sustained glucose production and tissues with altered use of glucose and lactate in cxC26 mice. We provide a comprehensive view of metabolic alterations in cancer cachexia revealing those distinct from decreased nutrient intake.<\/jats:p>\n                <jats:sec>\n                  <jats:title>Highlights<\/jats:title>\n                  <jats:p>\n                    <jats:list list-type=\"bullet\">\n                      <jats:list-item>\n                        <jats:p>Quantitative fluxomics of cancer cachexia under matched food intake and body weight<\/jats:p>\n                      <\/jats:list-item>\n                      <jats:list-item>\n                        <jats:p>Intact lipolysis, proteolysis, ketogenesis, and lipid oxidation in cachectic mice<\/jats:p>\n                      <\/jats:list-item>\n                      <jats:list-item>\n                        <jats:p>Sustained glucose consumption in cachectic mice despite reduced food intake<\/jats:p>\n                      <\/jats:list-item>\n                      <jats:list-item>\n                        <jats:p>Increased glucose production from glutamine and alanine in cachectic mice<\/jats:p>\n                      <\/jats:list-item>\n                    <\/jats:list>\n                  <\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2025.05.15.654370","type":"posted-content","created":{"date-parts":[[2025,5,20]],"date-time":"2025-05-20T08:40:16Z","timestamp":1747730416000},"source":"Crossref","is-referenced-by-count":3,"title":["Sustained Glucose Turnover Flux Distinguishes Cancer Cachexia from Nutrient Limitation"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1472-5726","authenticated-orcid":false,"given":"Young-Yon","family":"Kwon","sequence":"first","affiliation":[{"name":"Department of Molecular Metabolism, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5783-1636","authenticated-orcid":false,"given":"Yanshan","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Molecular Metabolism, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3682-9219","authenticated-orcid":false,"given":"Maria","family":"Gomez-Jenkins","sequence":"additional","affiliation":[{"name":"Rutgers Cancer Institute, New Brunswick, NJ 08901, USA"},{"name":"Ludwig Princeton Branch, Ludwig Institute for Cancer Research, Princeton University, Princeton, NJ 08544, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mujmmail","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Department of Medicine, NYU Langone Health, New York, NY 10016, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangru","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Molecular Metabolism, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliya","family":"Hsiang","sequence":"additional","affiliation":[{"name":"Department of Molecular Metabolism, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9329-1326","authenticated-orcid":false,"given":"David Y.","family":"Lewis","sequence":"additional","affiliation":[{"name":"The Beatson Institute for Cancer Research, Cancer Research UK, Glasgow G61 1BD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7820-3727","authenticated-orcid":false,"given":"Tobias","family":"Janowitz","sequence":"additional","affiliation":[{"name":"Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA"},{"name":"Northwell Health Cancer Institute, Northwell Health, New Hyde Park, NY 11042, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0784-9248","authenticated-orcid":false,"given":"Marcus D.","family":"Goncalves","sequence":"additional","affiliation":[{"name":"Department of Medicine, NYU Langone Health, New York, NY 10016, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2961-3065","authenticated-orcid":false,"given":"Eileen","family":"White","sequence":"additional","affiliation":[{"name":"Rutgers Cancer Institute, New Brunswick, NJ 08901, USA"},{"name":"Ludwig Princeton Branch, Ludwig Institute for Cancer Research, Princeton University, Princeton, NJ 08544, USA"},{"name":"Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, NJ 08903 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4226-6806","authenticated-orcid":false,"given":"Sheng","family":"Hui","sequence":"additional","affiliation":[{"name":"Department of Molecular Metabolism, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026041122391274000_2025.05.15.654370v1.1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-06-4585"},{"key":"2026041122391274000_2025.05.15.654370v1.2","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2017.105"},{"key":"2026041122391274000_2025.05.15.654370v1.3","doi-asserted-by":"publisher","DOI":"10.1038\/s42255-024-01167-9"},{"key":"2026041122391274000_2025.05.15.654370v1.4","doi-asserted-by":"publisher","DOI":"10.1101\/gad.320481.118"},{"key":"2026041122391274000_2025.05.15.654370v1.5","doi-asserted-by":"crossref","unstructured":"Bonetto, A. , Rupert, J.E. , Barreto, R. , and Zimmers, T.A . (2016). The Colon-26 Carcinoma Tumor-bearing Mouse as a Model for the Study of Cancer Cachexia. J Vis Exp.","DOI":"10.3791\/54893"},{"key":"2026041122391274000_2025.05.15.654370v1.6","first-page":"2142","article-title":"Establishment of mouse colonic carcinoma cell lines with different metastatic properties","volume":"40","year":"1980","journal-title":"Cancer Res"},{"key":"2026041122391274000_2025.05.15.654370v1.7","doi-asserted-by":"publisher","DOI":"10.1200\/JOP.2016.016832"},{"key":"2026041122391274000_2025.05.15.654370v1.8","doi-asserted-by":"publisher","DOI":"10.1007\/s00259-024-06836-1"},{"key":"2026041122391274000_2025.05.15.654370v1.9","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.12270"},{"key":"2026041122391274000_2025.05.15.654370v1.10","doi-asserted-by":"publisher","DOI":"10.1111\/j.1349-7006.2010.01582.x"},{"key":"2026041122391274000_2025.05.15.654370v1.11","doi-asserted-by":"publisher","DOI":"10.1017\/S0029665118002811"},{"key":"2026041122391274000_2025.05.15.654370v1.12","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2017-01020"},{"key":"2026041122391274000_2025.05.15.654370v1.13","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1249\/MSS.0000000000002166","article-title":"Cachexia Disrupts Diurnal Regulation of Activity, Feeding, and Muscle Mechanistic Target of Rapamycin Complex 1 in Mice","volume":"52","year":"2020","journal-title":"Med Sci Sports Exerc"},{"key":"2026041122391274000_2025.05.15.654370v1.14","doi-asserted-by":"publisher","DOI":"10.1007\/s11306-012-0485-6"},{"key":"2026041122391274000_2025.05.15.654370v1.15","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-024-08026-3"},{"key":"2026041122391274000_2025.05.15.654370v1.16","doi-asserted-by":"publisher","DOI":"10.1016\/S0899-9007(99)00095-7"},{"key":"2026041122391274000_2025.05.15.654370v1.17","doi-asserted-by":"publisher","DOI":"10.1016\/j.clnu.2008.06.013"},{"key":"2026041122391274000_2025.05.15.654370v1.18","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.12059"},{"key":"2026041122391274000_2025.05.15.654370v1.19","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-cancerbio-050216-121954"},{"key":"2026041122391274000_2025.05.15.654370v1.20","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2023.03.028"},{"key":"2026041122391274000_2025.05.15.654370v1.21","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2016.10.010"},{"key":"2026041122391274000_2025.05.15.654370v1.22","doi-asserted-by":"crossref","unstructured":"Garcia-Flores, L.A. , Green, C.L. , Mitchell, S.E. , Promislow, D.E.L. , Lusseau, D. , Douglas, A. , and Speakman, J.R . (2021). The effects of graded calorie restriction XVII: Multitissue metabolomics reveals synthesis of carnitine and NAD, and tRNA charging as key pathways. Proc Natl Acad Sci U S A 118.","DOI":"10.1073\/pnas.2101977118"},{"key":"2026041122391274000_2025.05.15.654370v1.23","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1714703115"},{"key":"2026041122391274000_2025.05.15.654370v1.24","doi-asserted-by":"publisher","DOI":"10.1101\/gad.219642.113"},{"key":"2026041122391274000_2025.05.15.654370v1.25","first-page":"3710","article-title":"Altered glucose metabolism in metastatic carcinoma","volume":"35","year":"1975","journal-title":"Cancer Res"},{"key":"2026041122391274000_2025.05.15.654370v1.26","first-page":"5910","article-title":"Glucose metabolism in cachectic patients with colorectal cancer","volume":"44","year":"1984","journal-title":"Cancer Res"},{"key":"2026041122391274000_2025.05.15.654370v1.27","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2020.07.013"},{"key":"2026041122391274000_2025.05.15.654370v1.28","doi-asserted-by":"publisher","DOI":"10.1038\/nature24057"},{"key":"2026041122391274000_2025.05.15.654370v1.29","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-05-2193"},{"key":"2026041122391274000_2025.05.15.654370v1.30","doi-asserted-by":"publisher","DOI":"10.1016\/0026-0495(86)90145-9"},{"key":"2026041122391274000_2025.05.15.654370v1.31","doi-asserted-by":"publisher","DOI":"10.1038\/nature06030"},{"key":"2026041122391274000_2025.05.15.654370v1.32","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2022.111947"},{"key":"2026041122391274000_2025.05.15.654370v1.33","doi-asserted-by":"publisher","DOI":"10.1038\/nature13528"},{"key":"2026041122391274000_2025.05.15.654370v1.34","doi-asserted-by":"publisher","DOI":"10.1038\/s44319-024-00144-3"},{"key":"2026041122391274000_2025.05.15.654370v1.35","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2301215120"},{"key":"2026041122391274000_2025.05.15.654370v1.36","doi-asserted-by":"publisher","DOI":"10.1016\/0026-0495(87)90132-6"},{"key":"2026041122391274000_2025.05.15.654370v1.37","doi-asserted-by":"crossref","unstructured":"Liang, Y. , Kwon, Y.-Y. , and Hui, S. (2025). Separating anorexia -dependent and - independent effects in cancer cachexia. bioRxiv, 2025.2004.2024.650538.","DOI":"10.1101\/2025.04.24.650538"},{"key":"2026041122391274000_2025.05.15.654370v1.38","doi-asserted-by":"publisher","DOI":"10.1038\/s42255-025-01265-2"},{"key":"2026041122391274000_2025.05.15.654370v1.39","first-page":"4807","article-title":"Efflux of 3-methylhistidine from the leg in cancer patients who experience weight loss","volume":"42","year":"1982","journal-title":"Cancer Res"},{"key":"2026041122391274000_2025.05.15.654370v1.40","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2013.09.002"},{"key":"2026041122391274000_2025.05.15.654370v1.41","doi-asserted-by":"publisher","DOI":"10.1097\/00000658-198108000-00001"},{"key":"2026041122391274000_2025.05.15.654370v1.42","doi-asserted-by":"publisher","DOI":"10.1172\/JCI117651"},{"key":"2026041122391274000_2025.05.15.654370v1.43","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2022.900712"},{"key":"2026041122391274000_2025.05.15.654370v1.44","doi-asserted-by":"publisher","DOI":"10.1038\/s42255-021-00466-9"},{"key":"2026041122391274000_2025.05.15.654370v1.45","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-11-1095"},{"key":"2026041122391274000_2025.05.15.654370v1.46","doi-asserted-by":"crossref","unstructured":"Petruzzelli, M. , Ferrer, M. , Schuijs, M.J. , Kleeman, S.O. , Mourikis, N. , Hall, Z. , Perera, D. , Raghunathan, S. , Vacca, M. , Gaude, E. , et al. (2022). Early Neutrophilia Marked by Aerobic Glycolysis Sustains Host Metabolism and Delays Cancer Cachexia. Cancers (Basel) 14.","DOI":"10.3390\/cancers14040963"},{"key":"2026041122391274000_2025.05.15.654370v1.47","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.12360"},{"key":"2026041122391274000_2025.05.15.654370v1.48","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.12684"},{"key":"2026041122391274000_2025.05.15.654370v1.49","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-32135-0"},{"key":"2026041122391274000_2025.05.15.654370v1.50","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2018.02.019"},{"key":"2026041122391274000_2025.05.15.654370v1.51","unstructured":"Robert R. Wolfe, D.L.C. (2004). Isotope Tracers in Metabolic Research: Principles and Practice of Kinetic Analysis, 2nd Edition (Wiley-Liss)."},{"key":"2026041122391274000_2025.05.15.654370v1.52","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2013.00034"},{"key":"2026041122391274000_2025.05.15.654370v1.53","first-page":"E817","article-title":"Human kidney and liver gluconeogenesis: evidence for organ substrate selectivity","volume":"274","year":"1998","journal-title":"Am J Physiol"},{"key":"2026041122391274000_2025.05.15.654370v1.54","doi-asserted-by":"publisher","DOI":"10.1021\/acs.analchem.7b00396"},{"key":"2026041122391274000_2025.05.15.654370v1.55","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcancer.2016.01.002"},{"key":"2026041122391274000_2025.05.15.654370v1.56","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/nxaa166"},{"key":"2026041122391274000_2025.05.15.654370v1.57","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00016.2008"},{"key":"2026041122391274000_2025.05.15.654370v1.58","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2022.1023614"},{"key":"2026041122391274000_2025.05.15.654370v1.59","doi-asserted-by":"publisher","DOI":"10.1186\/s12986-022-00674-4"},{"key":"2026041122391274000_2025.05.15.654370v1.60","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2025.01.008"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2025.05.15.654370","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,12]],"date-time":"2026-04-12T05:39:18Z","timestamp":1775972358000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.1101\/2025.05.15.654370"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,20]]},"references-count":60,"URL":"https:\/\/doi.org\/10.1101\/2025.05.15.654370","relation":{},"subject":[],"published":{"date-parts":[[2025,5,20]]},"subtype":"preprint"}}