Year: 2026
Type: preprint
Abstract: ABSTRACT Background Cachexia is a multifactorial syndrome frequently observed in cancer patients, characterized by progressive weight loss, muscle atrophy, and systemic inflammation. We recently demonstrated that supplementation with FuFA-F2, a naturally occurring lipid found in various foods, increases muscle mass in different metabolic contexts. Here, we investigated whether FuFA-F2 supplementation could prevent tumor-induced muscle wasting and preserve skeletal muscle integrity during cancer cachexia. Methods In vitro , C2C12 myotubes were exposed to TNFα and IFNγ to mimic cachectic conditions, and the effects of FuFA-F2 on myotube morphology were assessed. In vivo , cancer cachexia was induced by subcutaneous injection of C26 adenocarcinoma cells into male CD2F1 mice. Three groups were compared: non-grafted control mice, untreated C26 tumor-bearing mice, and C26 tumor-bearing mice orally supplemented with FuFA-F2 (13 mg/kg/day) for 14 days. Results In C2C12 myotubes, TNFα and IFNγ exposure reduced myotube area by 17% (p < 0.05), whereas FuFA-F2 treatment prevented this atrophy and restored myotube area to control levels (p < 0.05). In vivo , FuFA-F2 supplementation prevented muscle wasting in C26 tumor-bearing mice without affecting tumor growth or the loss of white adipose tissue. After 14 days, hindlimb muscle weight was reduced by 22% in C26 mice compared with controls (0.706 vs. 0.903 g, p < 0.05), whereas muscle weight in FuFA-F2-treated mice (0.835 g) was not significantly different from controls. Consistently, spontaneous wheel activity was markedly reduced in C26 mice during the final four days (-79%; 3.4 vs. 16.5 km, p < 0.05), whereas FuFA-F2- treated mice maintained activity levels closer to those of controls (11.2 km). RNA-seq analysis revealed extensive transcriptional reprogramming of skeletal muscle in response to C26 tumor growth, with 5,465 differentially expressed genes (DEGs; 32% of detected genes) between Control and C26 mice. Notably, FuFA- F2 substantially attenuated this response, with only 366 DEGs (2%) between Control and C26 + FuFA-F2 mice, and principal component analysis (PCA) showed a transcriptomic profile closer to controls. Tumor- induced alterations involved pathways related to proteostasis, inflammation, and tissue remodeling, which were largely prevented or attenuated by FuFA-F2. Consistent with these findings, FuFA-F2 prevented the induction of Myostatin , Activin A , MAFbx and MuRF1 , and attenuated muscle fibrosis and local inflammation. Conclusions These findings demonstrate that FuFA-F2 preserves skeletal muscle mass and function in the C26 model of cancer cachexia, despite ongoing tumor progression. FuFA-F2 markedly attenuates tumor- induced transcriptional reprogramming and associated catabolic, inflammatory and fibrotic responses, supporting its potential as a therapeutic strategy to preserve skeletal muscle during cancer cachexia.
Authors: Anaïs Deglos, Jennifer Falconi, Charles Géminard, Christelle Bertrand-Gaday, Béatrice Bonafos, Vanessa Bauer, Lisa Heron-Milhavet, Erwann Durand, Pierre Delobel, Céline Jahannault-Talignani, Cécile Déjou, Anna Carval, Jatuporn Chaiyut, Laurent Vaysse, Siriluck Liengprayoon, Laurence Pessemesse, Charles Coudray, Walter Vetter, Christine Feillet-Coudray, Alexandre Djiane, François Casas
Institutions: Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement, Dynamique du Muscle et Métabolisme, Inserm, Institut de Recherche en Cancérologie de Montpellier, University of Hohenheim, Centre de Coopération Internationale en Recherche Agronomique pour le Développement, Université de Montpellier, University of Reunion Island, Institut de Recherche pour le Développement, UMR QualiSud, L'Institut Agro, Kasetsart University, Biomasse, bois, énergie, bio-produits
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7212316456