Sustained Glucose Turnover Flux Distinguishes Cancer Cachexia from Nutrient Limitation

Kwon, Young-Yon, Liang, Yanshan, Gomez-Jenkins, Maria, Ahmed, Mujmmail, Jiang, Guangru, Hsiang, Juliya, Lewis, David Y, Janowitz, Tobias, Goncalves, Marcus D, White, Eileen, Hui, Sheng (May 2025) Sustained Glucose Turnover Flux Distinguishes Cancer Cachexia from Nutrient Limitation. bioRxiv. ISSN 2692-8205 (Submitted)

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Abstract

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.

Item Type:	Paper
Subjects:	diseases & disorders > cancer diseases & disorders diseases & disorders > nutritional and metabolic diseases diseases & disorders > nutritional and metabolic diseases > cachexia
CSHL Authors:	Janowitz, Tobias
Communities:	CSHL labs > Janowitz lab
SWORD Depositor:	CSHL Elements
Depositing User:	CSHL Elements
Date:	20 May 2025
Date Deposited:	11 Jun 2025 17:59
Last Modified:	11 Jun 2025 17:59
PMCID:	PMC12139815
Related URLs:	Publisher
URI:	https://repository.cshl.edu/id/eprint/41887

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