Evidence mapPaperPMID 42468841Full record

ArticleMolecular metabolism2026

Pre-clinical cancer cachexia causes glucose hypermetabolism prior to overt weight loss.

Emma Frank, Kaspar W Persson, Pauline Morigny, Zakarias Kefil Jensen Ogueboule, Tang Cam Phung Pham, Jonas R Knudsen, Maria Rohm, Lykke Sylow, Steffen H Raun

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Article in Molecular metabolism, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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4 · The record

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5 · Who and what money

Authors and funding

9 authors.

Emma FrankThe Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Kaspar W PerssonDepartment of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Denmark.
Pauline MorignyInstitute for Diabetes and Cancer (IDC), Helmholtz Munich, Neuherberg, Germany; Joint Heidelberg-IDC Translational Diabetes Program, University Hospital, Heidelberg, Germany; German Center for Diabetes Research (DZD), Munich, Germany.
Zakarias Kefil Jensen OguebouleThe Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Tang Cam Phung PhamThe Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Institute for Mitochondrial Diseases and Aging, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD) and Center for Molecular Medicine (CMMC), Medical Faculty, University of Cologne, Cologne, Germany.
Jonas R KnudsenDepartment of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Denmark.
Maria RohmInstitute for Diabetes and Cancer (IDC), Helmholtz Munich, Neuherberg, Germany; Joint Heidelberg-IDC Translational Diabetes Program, University Hospital, Heidelberg, Germany; German Center for Diabetes Research (DZD), Munich, Germany.
Lykke SylowThe Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. Electronic address: Lykkesylow@sund.ku.dk.
Steffen H RaunThe Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. Electronic address: steffenraun@sund.ku.dk.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeCancer cachexia is a life-threatening complication of advanced malignancies, driven by profound systemic metabolic reprogramming and anorexia. Insulin action is markedly impaired in patients with cancer and may contribute directly to cachexia pathogenesis. However, the interplay between weight loss, food intake, and cancer-associated metabolic rewiring in cachexia remains poorly defined. Clarifying this relationship is essential for identifying the fundamental drivers of cachexia and for developing effective therapeutic strategies.

methodsWe assessed metabolic rewiring by temporal evaluation of glucose tolerance and isotopic tracers to determine muscle insulin-stimulated glucose uptake in male cachectic and non-cachectic C26- and KPC-tumor-bearing, as well as healthy mice undergoing food restriction.

resultsCachectic C26- and KPC-tumor mice showed increased glucose tolerance compared to non-tumor-bearing control mice, and non-cachectic tumor-bearing mice. Increased glucose tolerance appeared prior to overt muscle loss, independent of tumor size and changes in food intake. Ex vivo insulin-stimulated glucose uptake was elevated in soleus (+78%) and extensor digitorum longus (+35%) muscle from cachectic C26-tumor mice with anorexia compared to weight stable C26-tumor mice and control mice. This increase was associated with enhanced AKT signaling. Food restriction in healthy mice increased glucose tolerance, insulin-stimulated glucose uptake ex vivo, and AKT signaling.

conclusionsOur findings suggest that glucose hypermetabolism appears prior to overt weight loss in pre-clinical cachexia, whereas late-stage cachexia with anorexia increased skeletal muscle insulin responsiveness. This highlights AKT signaling as a key node connecting nutrient status with muscle metabolism in cancer cachexia.

Indexed as

Cancer cachexiaFood restrictionGlucose metabolismInsulin sensitivityMuscle

Identifiers

PMID42468841
PMCPMC13463797

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.