Furan fatty acid supplementation protects against muscle atrophy during cancer cachexia
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 TNF and IFN{gamma} 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, TNF and IFN{gamma} 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.
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BibTeX
@misc{deglos2026furan,
title = {{Furan fatty acid supplementation protects against muscle atrophy during cancer cachexia}},
author = {Anaïs Deglos and Jennifer Falconi and Charles Géminard and Christelle Bertrand-Gaday and Béatrice Bonafos and Vanessa Bauer and Lisa Heron-Milhavet and Erwann Durand and Pierre Delobel and Céline Jahannault-Talignani and Cécile Dejoux and Anna Carval and Jatuporn Chaiyut and Laurent Vaysse and Siriluck Liengprayoon and Laurence Pessemesse and Charles Coudray and Walter Vetter and Christine Feillet-Coudray and Alexandre Djiane and François Casas},
howpublished = {BioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.08.750107},
url = {https://hal.inrae.fr/hal-05802426v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Furan fatty acid supplementation protects against muscle atrophy during cancer cachexia
AU - Anaïs Deglos
AU - Jennifer Falconi
AU - Charles Géminard
AU - Christelle Bertrand-Gaday
AU - Béatrice Bonafos
AU - Vanessa Bauer
AU - Lisa Heron-Milhavet
AU - Erwann Durand
AU - Pierre Delobel
AU - Céline Jahannault-Talignani
AU - Cécile Dejoux
AU - Anna Carval
AU - Jatuporn Chaiyut
AU - Laurent Vaysse
AU - Siriluck Liengprayoon
AU - Laurence Pessemesse
AU - Charles Coudray
AU - Walter Vetter
AU - Christine Feillet-Coudray
AU - Alexandre Djiane
AU - François Casas
PY - 2026
DA - 2026/09/08
PB - BioRxiv
DO - 10.64898/2026.09.08.750107
UR - https://hal.inrae.fr/hal-05802426v1
AB - 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 TNF and IFN{gamma} 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, TNF and IFN{gamma} 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.
SN - 2692-8205
ER -