Image de couverture de livre

Functional liver genomics identifies hepatokines promoting wasting in cancer cachexia

In cancer cachexia, the presence of a tumor triggers systemic metabolic disruption that leads to involuntary body weight loss and accelerated mortality in affected patients. Here, we conducted transcriptomic and epigenomic profiling of the liver in various weight-stable cancer and cancer cachexia mo...

Description complète

Enregistré dans:
Détails bibliographiques
Auteurs principaux: Kaltenecker, Doris (Auteur) , Fisker Schmidt, Søren (Auteur) , Weber, Peter (Auteur) , Loft, Anne (Auteur) , Morigny, Pauline (Auteur) , Machado, Juliano (Auteur) , Geppert, Julia (Auteur) , Saul, Kerstin Beate (Auteur) , Benedikt, Pia (Auteur) , Molocea, Claudia-Eveline (Auteur) , Scott, Rachel (Auteur) , Haase, Kerstin (Auteur) , Martignoni, Marc (Auteur) , Alfaro Nunez, Ana Jimena (Auteur) , Chow, Kan Kau (Auteur) , Simoes, Estefania (Auteur) , Pinhata Otoch, José (Auteur) , Lima, Joanna D. C. C. (Auteur) , Swanton, Charles (Auteur) , Spielmann, Nadine (Auteur) , Hrabě de Angelis, Martin (Auteur) , Elsner, Markus (Auteur) , Ertürk, Ali (Auteur) , Dyar, Kenneth A. (Auteur) , Rohm, Maria (Auteur) , Prokopchuk, Olga (Auteur) , Jamal-Hanjani, Mariam (Auteur) , Seelaender, Marilia (Auteur) , Backs, Johannes (Auteur) , Herzig, Stephan (Auteur) , Berriel Diaz, Mauricio (Auteur)
Format: Article (Journal)
Langue:anglais
Publié: August 21, 2025
In: Cell
Year: 2025, Volume: 188, Numéro: 17, Pages: 4549-4566
ISSN:1097-4172
DOI:10.1016/j.cell.2025.06.039
Accès en ligne:Resolving-System, kostenfrei, Volltext: https://doi.org/10.1016/j.cell.2025.06.039
Verlag, kostenfrei, Volltext: https://www.sciencedirect.com/science/article/pii/S009286742500741X
Accéder au texte intégral
Notes sur l'auteur:Doris Kaltenecker, Søren Fisker Schmidt, Peter Weber, Anne Loft, Pauline Morigny, Juliano Machado, Julia Geppert, Kerstin Beate Saul, Pia Benedikt, Claudia-Eveline Molocea, Rachel Scott, Kerstin Haase, Marc E. Martignoni, Ana Jimena Alfaro, Kan Kau Chow, Estefania Simoes, José Pinhata Otoch, Joanna D.C.C. Lima, Charles Swanton, Nadine Spielmann, Martin Hrabé de Angelis, Markus Elsner, Ali Ertürk, Kenneth A. Dyar, Maria Rohm, Olga Prokopchuk, Mariam Jamal-Hanjani, Marilia Seelaender, Johannes Backs, Stephan Herzig, and Mauricio Berriel Diaz
Description
Résumé:In cancer cachexia, the presence of a tumor triggers systemic metabolic disruption that leads to involuntary body weight loss and accelerated mortality in affected patients. Here, we conducted transcriptomic and epigenomic profiling of the liver in various weight-stable cancer and cancer cachexia models. An integrative multilevel analysis approach identified a distinct gene expression signature that included hepatocyte-secreted factors and the circadian clock component REV-ERBα as key modulator of hepatic transcriptional reprogramming in cancer cachexia. Notably, hepatocyte-specific genetic reconstitution of REV-ERBα in cachexia ameliorated peripheral tissue wasting. This improvement was associated with decreased levels of specific cachexia-controlled hepatocyte-secreted factors. These hepatokines promoted catabolism in multiple cell types and were elevated in cachectic cancer patients. Our findings reveal a mechanism by which the liver contributes to peripheral tissue wasting in cancer cachexia, offering perspectives for future therapeutic interventions.
Description:Gesehen am 27.05.2026
Description matérielle:Online Resource
ISSN:1097-4172
DOI:10.1016/j.cell.2025.06.039

Documents similaires