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  3. Multi-omics profiling of cachexia-targeted tissues reveals a spatio-temporally coordinated response to cancer

Multi-omics profiling of cachexia-targeted tissues reveals a spatio-temporally coordinated response to cancer

  • Nat Metab. 2026 Jan;8(1):237-259. doi: 10.1038/s42255-025-01434-3.
Pauline Morigny 1 2 3,  Michaela Vondrackova 4,  Honglei Ji 1 2 3,  Kristyna Brejchova 4,  Monika Krakovkova 4,  Konstantinos Makris 3 5,  Radka Trubacova 4,  Tuna F Samanci 1 2 3,  Doris Kaltenecker 1 2 3,  Su-Ping Ng 1 2 3,  Vignesh Karthikaisamy 1 2 3,  Sophia E Chrysostomou 6,  Anna Bidovec 6,  Mariana Ponce-de-Leon 5,  Tanja Krauss 7,  Claudine Seeliger 7 8,  Olga Prokopchuk 9,  Marc E Martignoni 9,  Melina Claussnitzer 10 11 12,  Hans Hauner 7 8 13,  Martina Schweiger 6 14,  Laure B Bindels 15 16,  Mauricio Berriel Diaz 1 2 3,  Stephan Herzig 1 2 3 17,  Dominik Lutter 3 5,  Ondrej Kuda 18,  Maria Rohm 19 20 21 22
Affiliations

Affiliations

  • 1 Institute for Diabetes and Cancer, Helmholtz Center Munich, Neuherberg, Germany.
  • 2 Joint Heidelberg-IDC Translational Diabetes Program, Inner Medicine 1, University Hospital, Heidelberg, Germany.
  • 3 German Center for Diabetes Research, Munich, Germany.
  • 4 Metabolism of Bioactive Lipids, Institute of Physiology of the Czech Academy of Sciences, Prague, Czech Republic.
  • 5 Computational Discovery Research, Institute for Diabetes and Obesity, Helmholtz Center Munich, Neuherberg, Germany.
  • 6 Institute of Molecular Biosciences, University of Graz, Graz, Austria.
  • 7 Else Kröner Fresenius Center for Nutritional Medicine, School of Life Sciences, Technical University of Munich, Freising-Weihenstephan, Germany.
  • 8 ZIEL Institute for Food and Health, Technical University of Munich, Freising-Weihenstephan, Germany.
  • 9 Department of Surgery, Klinikum rechts der Isar, School of Medicine, Technical University of Munich, Munich, Germany.
  • 10 The Novo Nordisk Foundation Center for Genomic Mechanisms of Disease, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • 11 Diabetes Unit and Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.
  • 12 Department of Medicine, Harvard Medical School, Boston, MA, USA.
  • 13 Institute of Nutritional Medicine, School of Medicine, Technical University of Munich, Munich, Germany.
  • 14 BioTechMed-Graz, Graz, Austria.
  • 15 Metabolism and Nutrition Research Group, Louvain Drug Research Institute, UCLouvain, Université catholique de Louvain, Brussels, Belgium.
  • 16 Welbio Department, WEL Research Institute, Wavre, Belgium.
  • 17 Chair Molecular Metabolic Control, Technical University Munich, Munich, Germany.
  • 18 Metabolism of Bioactive Lipids, Institute of Physiology of the Czech Academy of Sciences, Prague, Czech Republic. [email protected].
  • 19 Institute for Diabetes and Cancer, Helmholtz Center Munich, Neuherberg, Germany. [email protected].
  • 20 Joint Heidelberg-IDC Translational Diabetes Program, Inner Medicine 1, University Hospital, Heidelberg, Germany. [email protected].
  • 21 German Center for Diabetes Research, Munich, Germany. [email protected].
  • 22 German Center for Cardiovascular Research, partner site Munich Heart Alliance, Munich, Germany. [email protected].
PMID: 41540255 DOI: 10.1038/s42255-025-01434-3
Abstract

Cachexia is a wasting disorder associated with high morbidity and mortality in patients with Cancer. Tumour-host interaction and maladaptive metabolic reprogramming are substantial, yet poorly understood, contributors to cachexia. Here we present a comprehensive overview of the spatio-temporal metabolic reprogramming during cachexia, using integrated metabolomics, RNA Sequencing and 13C-glucose tracing data from multiple tissues and tumours of C26 tumour-bearing male mice at different disease stages. We identified one-carbon metabolism as a tissue-overarching pathway characteristic for metabolic wasting in mice and patients and linked to inflammation, glucose hypermetabolism and atrophy in muscle. The same metabolic rewiring also occurred in five additional mouse models, namely Panc02, 8025, APCMin, LLC and KPP, and a humanised cachexia mouse model. Together, our study provides a molecular framework for understanding metabolic reprogramming and the multi-tissue metabolite-coordinated response during Cancer cachexia progression, with one-carbon metabolism as a tissue-overarching mechanism linked to wasting.

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